Identification of immune-related candidate biomarkers in plasma of patients with sporadic vestibular schwannoma
Data files
Nov 06, 2023 version files 444.24 KB
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adf7295_manuscript_data_102423.xlsx
412.27 KB
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README.md
31.97 KB
Abstract
Vestibular schwannoma (VS) is an intracranial tumor arising from neoplastic Schwann cells, and typically presenting with hearing loss. The traditional belief that hearing deficit is caused by physical expansion of the VS, compressing the auditory nerve, does not explain the common clinical finding that patients with small tumors can have profound hearing loss, suggesting that tumor-secreted factors could influence hearing ability in VS patients. We conducted profiling of patients' plasma for 66 immune-related factors in patients with sporadic VS (N>170) and identified and validated candidate biomarkers associated with tumor size (S100B) and hearing (MCP-3). We further identified a 9-biomarker panel (TNR-R2, MIF, CD30, MCP-3, IL-2R, BLC, TWEAK, eotaxin, S100B) with outstanding discriminatory ability for VS. These findings revealed possible therapeutic targets for VS, providing a unique diagnostic tool that may predict hearing change and tumor growth in VS patients, and may inform the timing of tumor resection to preserve hearing.
README
This README file was generated on 2023-10-24 by Sasa Vasilijic.
GENERAL INFORMATION
- Title of Dataset: Identification of Immune-Related Candidate Biomarkers in Plasma of Patients with Sporadic Vestibular Schwannoma
- Author Information
First author Contact Information
Name: Sasa Vasilijic
Institution: Stanford University School of Medicine Address: 801 Welch Rd, Palo Alto, CA 94304, USA Email: vasilije@stanford.edu - Date of sample/data collection (single date, range, approximate date):
- Discovery cohort: 07/2015–04/2021
- Validation cohort: 08/2021-06/2023
Study subjects
- patients with sporadic vestibular schwannoma organized in discovery and validation cohorts
- healthy blood donors organized in discovery and validation cohorts
Samples
- human peripheral blood
Data
- demographics data: age and sex;
- clinical preoperative data: concentration of immuno-related factors detected in the plasma, pure tone average, word recognition score, tumor volume;
Abbreviations:
VS: vestibular schwannoma
PTA: pure tone average
WR: word recognition
- Geographic location of sample/ data collection:
- Discovery cohort patients: Massachusetts Eye and Ear (MEE), Boston, MA, USA
- Discovery cohort healthy controls: Research Blood Components, Watertown, MA, USA
- Validation cohort patients: Stanford Hospital, Palo Alto, CA, USA
- Validation cohort healthy controls: Stanford Hospital Blood Donor Center, Palo Alto, CA, USA
- Information about funding sources that supported the collection of the data: National Institute on Deafness and Other Communication Disorders grant R01 DC015824; Bertarelli Foundation Endowed Professorship at Stanford University; Remondi Foundation, and Larry Bowman.
SHARING/ACCESS INFORMATION
- Licenses/restrictions placed on the data: CC0 1.0 Universal (CC0 1.0) Public Domain
- Links to publications that cite or use the data:
Vasilijic S, Atai NA, Hyakusoku H, Worthington S, Ren Y, Sagers JE, Sahin MI, Fujita T, Landegger LD, Lewis R, Welling DB, Stankovic KM. Identification of Immune-Related Candidate Biomarkers in Plasma of Patients with Sporadic Vestibular Schwannoma. Science Advances 2023, http://www.science.org/doi/10.1126/sciadv.adf7295.
- Links to other publicly accessible locations of the data: None
- Links/relationships to ancillary data sets: None
- Was data derived from another source? No A. If yes, list source(s): NA
- Recommended citation for this dataset:
Vasilijic S, Atai NA, Hyakusoku H, Worthington S, Ren Y, Sagers JE, Sahin MI, Fujita T, Landegger LD, Lewis R, Welling DB, Stankovic KM. Data from: Identification of Immune-Related Candidate Biomarkers in Plasma of Patients with Sporadic Vestibular Schwannoma. Dryad Digital Repository. https://doi.org/10.5061/dryad.15dv41p3b.
DATA & FILE OVERVIEW
- File List:
adf7295_manuscript_data_101723.xlsx
- Relationship between files, if important: None
- Additional related data collected that was not included in the current data package: None
- Are there multiple versions of the dataset? No A. If yes, name of file(s) that was updated: NA i. Why was the file updated? NA ii. When was the file updated? NA
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_1A (Demographic and clinical characteristics of the VS patients and controls - Discovery cohort)
- Number of variables
- Vestibular schwannoma: 8
- Healthy donors: 8
- Number of cases/rows
- Vestibular schwannoma: 159
- Healthy donors: 70
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- Tumor Size (cm3)
- PTA (dB) Ipsilateral ear
- WR (%) Ipsilateral ear
- PTA (dB) Contralateral Ear
- WR (%) Contralateral Ear
- Hearing (good, poor)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_1B (Demographic and clinical characteristics of the VS patients and controls - Validation cohort)
- Number of variables
- Vestibular schwannoma: 8
- Healthy donors: 8
- Number of cases/rows
- Vestibular schwannoma: 50
- Healthy donors: 43
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- Tumor Size (cm3)
- PTA (dB) Ipsilateral ear
- WR (%) Ipsilateral ear
- PTA (dB) Contralateral Ear
- WR (%) Contralateral Ear
- Hearing (good, poor)
- Missing data codes: N/A (data not available), incomplete data
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_2A (candidate biomarker plasma levels in VS patients and controls- Discovery cohort)
- Number of variables
- Vestibular schwannoma: 22
- Healthy donors: 22
- Number of cases/rows
- Vestibular schwannoma: 159
- Healthy donors: 70
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- IL-2R (pg/mL)
- SDF-1α (pg/mL)
- TWEAK (pg/mL)
- IL-18 (pg/mL)
- CD30 (pg/mL)
- APRIL (pg/mL)
- IL-16 (pg/mL)
- TNF-R2 (pg/mL)
- MDC (pg/mL)
- MCP-1 (pg/mL)
- BLC (pg/mL)
- MIF (pg/mL)
- S-100B (pg/mL)
- HGF (pg/mL)
- Eotaxin-2 (pg/mL)
- VEGF-A (pg/mL)
- MCP-3 (pg/mL)
- IP-10 (pg/mL)
- Eotaxin (pg/mL)
- MCP-2 (pg/mL)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_2B (candidate biomarker plasma levels in VS patients and controls- Validation cohort)
- Number of variables
- Vestibular schwannoma: 15
- Healthy donors: 15
- Number of cases/rows
- Vestibular schwannoma: 50
- Healthy donors: 43
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- IL-2R (pg/mL)
- SDF-1α (pg/mL)
- TWEAK (pg/mL)
- CD30 (pg/mL)
- APRIL (pg/mL)
- IL-16 (pg/mL)
- TNF-R2 (pg/mL)
- BLC (pg/mL)
- MIF (pg/mL)
- S100B (pg/mL)
- MCP-3 (pg/mL)
- Eotaxin (pg/mL)
- MCP-2 (pg/mL)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_2C (candidate biomarker plasma levels ratio between VS patients and controls - Discovery cohort)
Data set-1
- Number of variables: 14
- Number of cases/rows
- Vestibular schwannoma: 53
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- TNF-R2 (pg/mL)
- IL-2R (pg/mL)
- MCP-3 (pg/mL)
- CD30 (pg/mL)
- TWEAK (pg/mL)
- MIF (pg/mL)
- APRIL (pg/mL)
- IL-16 (pg/mL)
- SDF-1α (pg/mL)
- MCP-2 (pg/mL)
- Eotaxin (pg/mL)
- BLC (pg/mL)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
Data set-2
- Number of variables: 14
- Number of cases/rows
- Healthy donors: 53
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- TNF-R2 (pg/mL)
- IL-2R (pg/mL)
- MCP-3 (pg/mL)
- CD30 (pg/mL)
- TWEAK (pg/mL)
- MIF (pg/mL)
- APRIL (pg/mL)
- IL-16 (pg/mL)
- SDF-1α (pg/mL)
- MCP-2 (pg/mL)
- Eotaxin (pg/mL)
- BLC (pg/mL)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
Data set-3
Comment: The data set represents the plasma level ratio of biomarker concentrations by dividing values from data set-1 with values in data set-2. Cases/rows in data set-1 and data set-2 are arranged that represent sex and age-matched pairs. The outlier values of the plasma ratio (gray labeled values) were identified using the Rout method in GraphPad Prism (v9.3.1; GraphPad Software, La Jolla, CA, US) by setting Q to 1% (alpha to 0.01). The outlier values are omitted from the analysis.
- Number of variables: 12
- Number of cases/rows:53
- Variable List
- TNF-R2 (ratio)
- IL-2R (ratio)
- MCP-3 (ratio)
- CD30 (ratio)
- TWEAK (ratio)
- MIF (ratio)
- APRIL (ratio)
- IL-16 (ratio)
- SDF-1α (ratio)
- MCP-2 (ratio)
- Eotaxin (ratio)
- BLC (ratio)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
Data set-4
- Number of variables: 3
- Number of cases/rows
- Vestibular schwannoma: 36
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- S100B (pg/mL)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
Data set-5
- Number of variables: 3
- Number of cases/rows
- Healthy donors: 36
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- S100B (pg/mL)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
Data set-6
Comment: The data set represents the plasma level ratio of biomarker concentrations by dividing values from data set-4 with values in data set-5. Cases/rows in data set-4 and data set-5 are arranged that represent sex and age-matched pairs. The outlier values of the plasma ratio (gray labeled values) were identified using the Rout method in GraphPad Prism (v9.3.1; GraphPad Software, La Jolla, CA, US) by setting Q to 1% (alpha to 0.01). The outlier values are omitted from the analysis
- Number of variables: 1
- Number of cases/rows: 36
- Variable List:
- S100B (ratio)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
Data set-7 (Fig_2C data)
- Number of variables: 13
- Number of cases/rows:53
Comment: Data set-3 and data set-6 were pooled, the outlier values were omitted and their place in a new data set is indicated with gray-colored cells named "Outlier".
- Variable List
- TNF-R2 (ratio)
- IL-2R (ratio)
- MCP-3 (ratio)
- CD30 (ratio)
- TWEAK (ratio)
- MIF (ratio)
- APRIL (ratio)
- S100B (ratio)
- IL-16 (ratio)
- SDF-1α (ratio)
- MCP-2 (ratio)
- Eotaxin (ratio)
- BLC (ratio)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_2D (candidate biomarker plasma levels ratio between VS patients and controls - Validation cohort)
Data set-1
- Number of variables: 15
- Number of cases/rows
- Vestibular schwannoma: 32
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- TNF-R2 (pg/mL)
- MIF (pg/mL)
- APRIL (pg/mL)
- SDF-1α (pg/mL)
- IL-2R (pg/mL)
- MCP-2 (pg/mL)
- CD30 (pg/mL)
- IL-16 (pg/mL)
- TWEAK (pg/mL)
- BLC (pg/mL)
- Eotaxin (pg/mL)
- MCP-3 (pg/mL)
- S100B (pg/mL)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
Data set-2
- Number of variables: 15
- Number of cases/rows
- Healthy donors: 32
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- TNF-R2 (pg/mL)
- MIF (pg/mL)
- APRIL (pg/mL)
- SDF-1α (pg/mL)
- IL-2R (pg/mL)
- MCP-2 (pg/mL)
- CD30 (pg/mL)
- IL-16 (pg/mL)
- TWEAK (pg/mL)
- BLC (pg/mL)
- Eotaxin (pg/mL)
- MCP-3 (pg/mL)
- S100B (pg/mL)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
Data set-3
Comment: The data set represents the plasma level ratio of biomarker concentrations by dividing values from data set-1 with values in data set-2. Cases/rows in data set-1 and data set-2 are arranged that represent sex and age-matched pairs. The outlier values of the plasma ratio (gray labeled values) were identified using the Rout method in GraphPad Prism (v9.3.1; GraphPad Software, La Jolla, CA, US) by setting Q to 1% (alpha to 0.01). The outlier values are omitted from the analysis.
- Number of variables: 13
- Number of cases/rows:32
- Variable List
- TNF-R2 (ratio)
- MIF (ratio)
- APRIL (ratio)
- SDF-1α (ratio)
- IL-2R (ratio)
- MCP-2 (ratio)
- CD30 (ratio)
- IL-16 (ratio)
- TWEAK (ratio)
- BLC (ratio)
- Eotaxin (ratio)
- MCP-3 (ratio)
- S100B (ratio)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
Data set-4 (Fig_2D data)
Comment: The data set represents the data for Fig_2D and contains the data from data set-3 whose outlier values were omitted and their place is indicated with gray-colored cells named "Outlier".
- Number of variables: 13
- Number of cases/rows:32
- Variable List
- TNF-R2 (ratio)
- MIF (ratio)
- APRIL (ratio)
- SDF-1α (ratio)
- IL-2R (ratio)
- MCP-2 (ratio)
- CD30 (ratio)
- IL-16 (ratio)
- TWEAK (ratio)
- BLC (ratio)
- Eotaxin (ratio)
- MCP-3 (ratio)
- S100B (ratio)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_3A, B, C (Association of MCP-3 levels and preoperative hearing- Discovery cohort)
- Number of variables: 6
- Number of cases/rows:78
- Variable List
- MCP-3 (pg/mL)
- Sex (F-female, M-male)
- Age (years)
- WR (%) Ipsilateral ear
- WR (%) Contralateral Ear
- Tumor volume (cm3)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_3D, E (MCP-3 levels and hearing serviceability- Discovery cohort)
- Number of variables: 6
- Number of cases/rows
- VS patients with serviceable hearing: 30
- VS patients with nonserviceable hearing: 45
- Variable List
- MCP-3 (pg/mL)
- Sex (F-female, M-male)
- Age (years)
- Tumor volume (cm3)
- PTA (dB) Ipsilateral Ear
- WR (%) Ipsilateral ear
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_3F (WR and hearing serviceability- Discovery cohort)
- Number of variables: 3
- Number of cases/rows
- VS patients with serviceable hearing: 59
- VS patients with nonserviceable hearing: 59
- Variable List
- Age (years)
- Sex (F-female, M-male)
- WR (%) Ipsilateral ear
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_3G, H, I (Association of MCP-3 levels and preoperative hearing- Validation cohort-A)
- Number of variables: 6
- Number of cases/rows:50
- Variable List
- MCP-3 (pg/mL)
- Sex (F-female, M-male)
- Age (years)
- WR (%) Ipsilateral ear
- WR (%) Contralateral Ear
- Tumor volume (cm3)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_3J, K (MCP-3 levels and hearing serviceability- Validation cohort-A)
- Number of variables: 6
- Number of cases/rows
- VS patients with serviceable hearing: 22
- VS patients with nonserviceable hearing: 23
- Variable List
- MCP-3 (pg/mL)
- Sex (F-female, M-male)
- Age (years)
- Tumor volume (cm3)
- PTA (dB) Ipsilateral Ear
- WR (%) Ipsilateral ear
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_3L (WR and hearing serviceability- Validation cohort-A)
- Number of variables: 3
- Number of cases/rows
- VS patients with serviceable hearing: 15
- VS patients with nonserviceable hearing: 15
- Variable List
- Age (years)
- Sex (F-female, M-male)
- WR (%) Ipsilateral ear
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_3M, N, O (Association of MCP-3 levels and preoperative hearing- Validation cohort-B)
- Number of variables: 6
- Number of cases/rows:63
- Variable List
- MCP-3 (pg/mL)
- Sex (F-female, M-male)
- Age (years)
- WR (%) Ipsilateral ear
- WR (%) Contralateral Ear
- Tumor volume (cm3)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_3P, Q (MCP-3 levels and hearing serviceability- Validation cohort-B)
- Number of variables: 6
- Number of cases/rows
- VS patients with serviceable hearing: 27
- VS patients with nonserviceable hearing: 30
- Variable List
- MCP-3 (pg/mL)
- Sex (F-female, M-male)
- Age (years)
- Tumor volume (cm3)
- PTA (dB) Ipsilateral Ear
- WR (%) Ipsilateral ear
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_3R (WR and hearing serviceability- Validation cohort-B)
- Number of variables: 3
- Number of cases/rows
- VS patients with serviceable hearing: 26
- VS patients with nonserviceable hearing: 26
- Variable List
- Age (years)
- Sex (F-female, M-male)
- WR (%) Ipsilateral ear
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_4A, B, C (Association of S100B levels and preoperative tumor volume- Discovery cohort)
- Number of variables: 4
- Number of cases/rows:122
- Variable List
- S100B (pg/mL)
- Sex (F-female, M-male)
- Age (years)
- Tumor volume (mm3)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_4D, E (S100B levels and tumor resection- Discovery cohort)
- Number of variables: 4
- Number of cases/rows
- VS patients with gross tumor resection: 88
- VS patients with subtotal tumor resection: 34
- Variable List
- S100B (pg/mL)
- Sex (F-female, M-male)
- Age (years)
- Tumor volume (mm3)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_4F (Tumor volume and tumor resection- Discovery cohort)
- Number of variables: 3
- Number of cases/rows
- VS patients with gross tumor resection: 36
- VS patients with subtotal tumor resection: 36
- Variable List
- Age (years)
- Sex (F-female, M-male)
- Tumor volume (mm3)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_4G, H, I (Association of S100B levels and preoperative tumor volume- Validation cohort-A)
- Number of variables: 4
- Number of cases/rows:50
- Variable List
- S100B (pg/mL)
- Sex (F-female, M-male)
- Age (years)
- Tumor volume (mm3)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_4J, K (S100B levels and tumor resection- Validation cohort-A)
- Number of variables: 4
- Number of cases/rows
- VS patients with gross tumor resection: 17
- VS patients with subtotal tumor resection: 11
- Variable List
- S100B (pg/mL)
- Sex (F-female, M-male)
- Age (years)
- Tumor volume (mm3)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_4L (Tumor volume and tumor resection- Validation cohort-A)
- Number of variables: 3
- Number of cases/rows
- VS patients with gross tumor resection: 11
- VS patients with subtotal tumor resection: 11
- Variable List
- Age (years)
- Sex (F-female, M-male)
- Tumor volume (mm3)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_4M, N, O (Association of S100B levels and preoperative tumor volume- Validation cohort-B)
- Number of variables: 4
- Number of cases/rows:86
- Variable List
- S100B (pg/mL)
- Sex (F-female, M-male)
- Age (years)
- Tumor volume (mm3)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_4P, Q (S100B levels and tumor resection- Validation cohort-B)
- Number of variables: 4
- Number of cases/rows
- VS patients with gross tumor resection: 44
- VS patients with subtotal tumor resection: 20
- Variable List
- S100B (pg/mL)
- Sex (F-female, M-male)
- Age (years)
- Tumor volume (mm3)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_4R (Tumor volume and tumor resection- Validation cohort-B)
- Number of variables: 3
- Number of cases/rows
- VS patients with gross tumor resection: 17
- VS patients with subtotal tumor resection: 17
- Variable List
- Age (years)
- Sex (F-female, M-male)
- Tumor volume (mm3)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_5A (data used in ROC analysis- Discovery cohort)
- Number of variables: 11
- Number of cases/rows
- Vestibular schwannoma: 24
- Healthy donors: 24
- Variable List
- Age (years)
- Sex (F-female, M-male)
- TNF-R2 (pg/mL)
- MIF (pg/mL)
- CD30 (pg/mL)
- MCP-3 (pg/mL)
- IL-2R (pg/mL)
- BLC (pg/mL)
- TWEAK (pg/mL)
- Eotaxin (pg/mL)
- S-100B (pg/mL)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None #########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_5B (data used in ROC analysis- Validation cohort)
- Number of variables: 11
- Number of cases/rows
- Vestibular schwannoma: 32
- Healthy donors: 32
- Variable List
- Age (years)
- Sex (F-female, M-male)
- TNF-R2 (pg/mL)
- MIF (pg/mL)
- CD30 (pg/mL)
- MCP-3 (pg/mL)
- IL-2R (pg/mL)
- BLC (pg/mL)
- TWEAK (pg/mL)
- Eotaxin (pg/mL)
- S-100B (pg/mL)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None #########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_6A, C (data used in combinatorial ROC analysis, 10-fold cross-validation test, and AUC permutation test- Discovery cohort)
- Number of variables: 11
- Number of cases/rows
- Vestibular schwannoma: 24
- Healthy donors: 24
- Variable List
- Age (years)
- Sex (F-female, M-male)
- TNF-R2 (pg/mL)
- MIF (pg/mL)
- CD30 (pg/mL)
- MCP-3 (pg/mL)
- IL-2R (pg/mL)
- BLC (pg/mL)
- TWEAK (pg/mL)
- Eotaxin (pg/mL)
- S-100B (pg/mL)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None #########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_6B, D (data used in combinatorial ROC analysis, 10-fold cross-validation test, and AUC permutation test- Validation cohort)
- Number of variables: 11
- Number of cases/rows
- Vestibular schwannoma: 32
- Healthy donors: 32
- Variable List
- Age (years)
- Sex (F-female, M-male)
- TNF-R2 (pg/mL)
- MIF (pg/mL)
- CD30 (pg/mL)
- MCP-3 (pg/mL)
- IL-2R (pg/mL)
- BLC (pg/mL)
- TWEAK (pg/mL)
- Eotaxin (pg/mL)
- S-100B (pg/mL)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None #########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_S2A (Hearing characteristics of VS patients- Discovery cohort)
- Number of variables: 16
- Number of cases/rows
- VS patients: 154
- Variable List
- Audiometric threshold (dB) at 250 Hz Ipsilateral ear
- Audiometric threshold (dB) at 500 Hz Ipsilateral ear
- Audiometric threshold (dB) at 1000 Hz Ipsilateral ear
- Audiometric threshold (dB) at 2000 Hz Ipsilateral ear
- Audiometric threshold (dB) at 3000 Hz Ipsilateral ear
- Audiometric threshold (dB) at 4000 Hz Ipsilateral ear
- Audiometric threshold (dB) at 8000 Hz Ipsilateral ear
- Audiometric threshold (dB) at 250 Hz Contralateral ear
- Audiometric threshold (dB) at 500 Hz Contralateral ear
- Audiometric threshold (dB) at 1000 Hz Contralateral ear
- Audiometric threshold (dB) at 2000 Hz Contralateral ear
- Audiometric threshold (dB) at 3000 Hz Contralateral ear
- Audiometric threshold (dB) at 4000 Hz Contralateral ear
- Audiometric threshold (dB) at 8000 Hz Contralateral ear
- WR (%) Ipsilateral ear
- WR (%) Contralateral ear
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None #########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_S2B (Hearing characteristics of VS patients- Validation cohort)
- Number of variables: 16
- Number of cases/rows
- VS patients: 33
- Variable List
- Audiometric threshold (dB) at 250 Hz Ipsilateral ear
- Audiometric threshold (dB) at 500 Hz Ipsilateral ear
- Audiometric threshold (dB) at 1000 Hz Ipsilateral ear
- Audiometric threshold (dB) at 2000 Hz Ipsilateral ear
- Audiometric threshold (dB) at 3000 Hz Ipsilateral ear
- Audiometric threshold (dB) at 4000 Hz Ipsilateral ear
- Audiometric threshold (dB) at 8000 Hz Ipsilateral ear
- Audiometric threshold (dB) at 250 Hz Contralateral ear
- Audiometric threshold (dB) at 500 Hz Contralateral ear
- Audiometric threshold (dB) at 1000 Hz Contralateral ear
- Audiometric threshold (dB) at 2000 Hz Contralateral ear
- Audiometric threshold (dB) at 3000 Hz Contralateral ear
- Audiometric threshold (dB) at 4000 Hz Contralateral ear
- Audiometric threshold (dB) at 8000 Hz Contralateral ear
- WR (%) Ipsilateral ear
- WR (%) Contralateral ear
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None #########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_S3
- Number of variables: 15
- Number of cases/rows
- Vestibular schwannoma: 159
- Healthy donors: 70
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- MCP-3 (pg/mL)
- CD30 (pg/mL)
- IL-2R (pg/mL)
- TWEAK (pg/mL)
- TNF-R2 (pg/mL)
- S-100B (pg/mL)
- MIF (pg/mL)
- BLC (pg/mL)
- SDF-1α (pg/mL)
- MCP-2 (pg/mL)
- Eotaxin (pg/mL)
- APRIL (pg/mL)
- IL-16 (pg/mL)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_S4
- Number of variables: 15
- Number of cases/rows
- Vestibular schwannoma: 159
- Good hearing: 34
- Poor hearing: 121
- Healthy donors: 70
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- IL-2R (pg/mL)
- SDF-1α (pg/mL)
- TWEAK (pg/mL)
- CD30 (pg/mL)
- IL-16 (pg/mL)
- APRIL (pg/mL)
- TNF-R2 (pg/mL)
- BLC (pg/mL)
- MIF (pg/mL)
- S-100B (pg/mL)
- MCP-3 (pg/mL)
- Eotaxin (pg/mL)
- MCP-2 (pg/mL)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None #########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_S5A
- Number of variables: 13
- Number of cases/rows
- Vestibular schwannoma (Poor hearing): 121
- Healthy donors: 70
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- IL-2R (pg/mL)
- SDF-1α (pg/mL)
- TWEAK (pg/mL)
- CD30 (pg/mL)
- TNF-R2 (pg/mL)
- BLC (pg/mL)
- MIF (pg/mL)
- S-100B (pg/mL)
- MCP-3 (pg/mL)
- Eotaxin (pg/mL)
- MCP-2 (pg/mL)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None #########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_S5B
- Number of variables: 14
- Number of cases/rows
- Vestibular schwannoma (Good hearing): 34
- Healthy donors: 70
- Variable List:
- Age (years)
- Sex (F-female, M-male)
- IL-2R (pg/mL)
- SDF-1α (pg/mL)
- TWEAK (pg/mL)
- CD30 (pg/mL)
- APRIL (pg/mL)
- IL-16 (pg/mL)
- TNF-R2 (pg/mL)
- BLC (pg/mL)
- MIF (pg/mL)
- S-100B (pg/mL)
- MCP-3 (pg/mL)
- Eotaxin (pg/mL)
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None #########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_S6
- Number of variables: 18
- Number of cases/rows
- VS patients with serviceable hearing: 71
- VS patients with nonserviceable hearing: 79
- Variable List:
- IL-2R (pg/mL)
- SDF-1α (pg/mL)
- TWEAK (pg/mL)
- CD30 (pg/mL)
- APRIL (pg/mL)
- IL-16 (pg/mL)
- TNF-R2 (pg/mL)
- BLC (pg/mL)
- MIF (pg/mL)
- S-100B (pg/mL)
- MCP-3 (pg/mL)
- Eotaxin (pg/mL)
- MCP-2 (pg/mL)
- Sex (F-female, M-male)
- Age (years)
- Tumor volume (cm3)
- PTA (dB) Ipsilateral ear
- WR (%) Ipsilateral ear
- Missing data codes: NA (data not available)
- Specialized formats or other abbreviations used: None #########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_S7 (Discovery cohort)
Data set-1
- Number of variables: 11
- Number of cases/rows
- Vestibular schwannoma: 24
- Healthy donors: 24
- Variable List
- Age (years)
- Sex (F-female, M-male)
- S-100B (pg/mL)
- BLC (pg/mL)
- CD30 (pg/mL)
- IL-2R (pg/mL)
- MCP-3 (pg/mL)
- MIF (pg/mL)
- TNF-R2 (pg/mL)
- TWEAK (pg/mL)
- Eotaxin (pg/mL)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
Data set-2, data set-3
Comment: The data sets represent a correlation matrix composed of Spearman r coefficients based on the correlation analysis performed for the data set-1, using GraphPad Prism (v9.3.1; GraphPad Software, La Jolla, CA, US). Correlation coefficients were used for the construction of the correlation networks shown in Fig_S7, using Cytoscape (Shannon P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks Genome Research 2003 Nov; 13(11):2498-504).
#########################################################################
DATA-SPECIFIC INFORMATION FOR: Fig_S7 (Validation cohort)
Data set-1
- Number of variables: 11
- Number of cases/rows
- Vestibular schwannoma: 32
- Healthy donors: 32
- Variable List
- Age (years)
- Sex (F-female, M-male)
- S-100B (pg/mL)
- BLC (pg/mL)
- CD30 (pg/mL)
- IL-2R (pg/mL)
- MCP-3 (pg/mL)
- MIF (pg/mL)
- TNF-R2 (pg/mL)
- TWEAK (pg/mL)
- Eotaxin (pg/mL)
- Missing data codes: N/A (data not available)
- Specialized formats or other abbreviations used: None
Data set-2, data set-3
Comment: The data sets represent a correlation matrix composed of Spearman r coefficients based on the correlation analysis performed for the data set-1, using GraphPad Prism (v9.3.1; GraphPad Software, La Jolla, CA, US). Correlation coefficients were used for the construction of the correlation networks shown in Fig_S7, using Cytoscape (Shannon P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks Genome Research 2003 Nov; 13(11):2498-504).
#########################################################################
Methods
Study population and specimen collection
From 07/2015–04/2021, blood was prospectively collected from patients undergoing VS resection at Massachusetts Eye and Ear (MEE) in Boston, MA on the day of surgery, typically within 30 minutes of inducing general anesthesia and ≥1 hour before tumor microdissection (discovery cohort). Blood was similarly prospectively collected from 08/2021–06/2023 at Stanford Hospital in Palo Alto, CA (validation cohort). Blood from controls was collected at the Massachusetts General Hospital (MGH) Blood Donor Center in Boston, MA, and the Research Blood Components in Watertown, MA for the discovery cohort, and from the Stanford Hospital Blood Donor Center in Palo Alto, CA for the validation cohort. At collection, fresh blood was stored in EDTA vacutainer tubes (Becton Dickinson, NY, US) and kept at 4˚C without freezing. The whole blood samples were centrifuged at 2000 g for 10 min at 4°C. Plasma was separated and spun at 2000 g for 5 min at 4°C. Centrifuged plasma was filtered through 0.8 μm filter units (MF-Millipore MCE membrane, SLAA033SB; Millipore, Burlington, MA, US) and stored at -80°C until further use.
Eligible patients had unilateral, sporadic VS that had not been previously resected or irradiated. Of 186 and 50 enrolled VS patients in the discovery and validation cohorts, 163 and 50 met inclusion criteria, respectively, and were included in the analyses for comparison with 70 and 43 controls, respectively.
Clinical data
Clinical and demographic data were collected from patient charts, operative reports, pathology reports, and pre-operative radiographic imaging. Patient variables included age at tissue collection; pre-surgical tumor volume measured via high-resolution axial contrast-enhanced T1-weighted brain MRI; internal auditory canal protocol; and pre-surgical pure-tone audiometric threshold and WR measurements. MRI and hearing tests were those nearest to resection, typically ≤3 months. WR was defined as the percentage of spoken monosyllabic words discernable from a list typically read at 70 dB or the level at which a patient's speech intelligibility curve plateaus. Pure-tone audiometric thresholds at 0.5, 1, 2, and 3 kHz were used to calculate the PTA. Hearing groups were defined according to the American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) Hearing Classification Guidelines. GH was defined as WR>70% and PTA<30 dB (AAO-HNS class A hearing). Otherwise, patients were classified as having PH (AAO-HNS class B, C and D hearing). A deaf ear was assigned a PTA of 125 dB and WR score of 0%. Serviceable hearing (SH) was defined as WR>50% and PTA<50 dB (AAO-HNS class A and B hearing). Otherwise, patients were classified as having non-serviceable hearing (NSH) (AAO-HNS class C and D hearing). Tumor resection was defined as GTR if there was complete tumor removal or a small tumor remnant no greater than 5x5x2 mm was left behind to preserve nerve integrity. Otherwise, it was defined as STR.
Biomarker measurements
Luminex (65 cytokines, chemokines, growth factors, and soluble receptors); electrochemoluminescence (IL-18, TNF-α, and FGF-2); and ELISA (S100B) assays were conducted as described in detail below. Potential biomarkers were defined as those detectable in the plasma of >75% of patients
Luminex assay
Simultaneous multiplex profiling of 65 immune-related factors composed of cytokines, chemokines, and growth factors was performed using a customized multiplex bead-based immunoassay - Immune Monitoring 65-Plex Human ProcartaPlex™ Panel (#EPX650-10065-901; ThermoFisher Scientific, Waltham, MA, US) according to manufacturer's instructions. The fluorescence-based signal was acquired on the Magpix instrument (Luminex, Austin, TX, US), and the values of analytes were calculated using ProcartaPlex Analyst 1.0 Software (ThermoFisher Scientific). The analytes with values below the lower limit of quantification in more than 75% of all samples were excluded from the analysis. For the accepted analytes, the values between 0 pg/mL and the lower limit of quantification, and those exceeding the upper limit of quantification, were approximated with the lowest and highest concentration representing these limits, respectively.
Electrochemiluminescence assay
The following candidate biomarkers were measured using electrochemiluminescence-based human assays from Meso Scale Diagnostics (MSD, Rockville, MD, US): IL-18 (U-PLEX Human IL-18), and TNF-α (U-PLEX Human TNF-α). All assays were conducted according to the manufacturer's protocols and signal detection was performed on the QuickPlex SQ 120 device (MSD). Pre-analytical data processing was done using MSD Discovery Workbench software (v4.0.12).
ELISA assay
The S100B ELISA Kit (#EZHS100B- 33K; EMD Millipore, Billerica, MA, US) was used to measure S100B protein levels in the plasma of VS patients and controls. ELISA assays were performed by adhering to the manufacturer's protocol. Absorbance was measured using Spectra MAX 190 plate Reader (Molecular Devices, Sunnyvale, CA, US), and the standard curve was plotted using SoftMax Pro software (v5.2; Molecular Devices, San Jose, CA, US).