A unified eIF1A+ luminal cells-centered hypoxic and “cold” tumor microenvironment promotes PCa progression among different subtypes
Data files
Jan 05, 2026 version files 1.08 GB
-
ADT01.tar.gz
95.08 MB
-
ADT02.tar.gz
39.56 MB
-
ADT03.tar.gz
80.56 MB
-
ADT04.tar.gz
80.98 MB
-
Expression_matrix_FPKM_counts_myccap_HHT_ADT.txt
2.56 MB
-
Expression_matrix_FPKM_counts_myccap_shEIF1A.txt
2.47 MB
-
HHT-01.tar.gz
86.43 MB
-
HHT-02.tar.gz
75.28 MB
-
HHT-03.tar.gz
75.44 MB
-
HHT-04.tar.gz
103.32 MB
-
IMC_profiling.csv
247.66 MB
-
README.md
6.70 KB
-
Ribo-seq_RPF_and_mRNA_fpkm.txt
652.65 KB
-
Treatment_naive-01.tar.gz
99.25 MB
-
Treatment_naive-02.tar.gz
91.25 MB
Abstract
Prostate cancer (PCa) is a malignancy with high heterogeneity arising from the tumor microenvironment (TME) and histological subtypes. To achieve superior clinical efficacy, it is imperative to identify unified progression drivers within such heterogeneity. Here, we applied imaging mass cytometry to stain 38 proteins on paracancerous, low-grade acinar adenocarcinoma (LgPAC), high-grade PAC (HgPAC), intraductal carcinoma (IDC), and ductal adenocarcinoma (DAC) tissues, identifying that established oncogenic factors (e.g., BRCA1, PSMA) showed limited capacity in distinguishing PCa prognosis; in contrast, eIF1A, a key translational initiation factor, was specifically overexpressed in high-risk subtype including HgPAC, IDC, and DAC, and correlated with tumor progression and poor prognosis. eIF1A + luminal epithelium (LE) demonstrated elevated expression of HIF-1α and its downstream targets, along with increased spatial exclusion of anticancer immune cells, including PD1 - T cells and CD163 - macrophages, which were validated by single-cell RNA sequencing (RNA-seq) analysis. Mechanistically, EIF1A knockdown or translation inhibitor homoharringtonine (HHT) impaired HIF-1α translation without affecting its transcription in vitro, and reduced tumor volume in preclinical subcutaneous tumor models, with RNA-seq and multiple immunofluorescence (mIF) analyses confirming significant suppression of hypoxia-associated pathways. Based on an ongoing investigator-initiated trial of PCa patients receiving neoadjuvant HHT combined with androgen deprivation, we observed pronounced inhibition of hypoxia and enhanced immune cell infiltration upon treatment through single-cell RNA-seq. This study firstly applies spatial proteomics to delineate conserved molecular features across histological subtypes, providing insights for the clinical management of PCa.
Dataset DOI: 10.5061/dryad.tqjq2bwb3
Description of the data and file structure
This dataset includes the spatial proteomic data of 38 proteins in 71 ROIs obtained from imaging mass cytometry (IMC). This dataset also includes single-cell RNA sequencing of 10 post-surgical prostate cancer tissues (4 underwent neoadjuvant androgen deprivation therapy [ADT], 4 underwent HHT + ADT therapy, and 2 treatment-naive). Moreover, this dataset contains RNA sequencing data from Myc-CaP subcutaneous tumors, including HHT+ADT vs vehicle and sh-EIF1A v.s. sh-NC.
Files and variables
File: IMC_profiling.csv
Description: The expression levels of target proteins in each cell of all ROIs. The imaging mass cytometry (IMC) is conducted on a prostate cancer tumor microarray. The expression levels represent the scaled "background-subtracted metal signal intensity" derived from IMC.
Variables
- CellID: Cell labeling number
- ROI: Region of Interest
- CD44: Protein
- AR: Protein
- IDH1: Protein
- HLAI: Protein
- P53: Protein
- CK5: Protein
- CollagenI: Protein
- cleavedCaspase-3: Protein
- CD31: Protein
- E-cadherin: Protein
- HIF1a: Protein
- CD45: Protein
- IDH2: Protein
- CD163: Protein
- IDO-1: Protein
- PD-L1: Protein
- VEGFA: Protein
- CD68: Protein
- PSMA: Protein
- CD20: Protein
- PTEN: Protein
- CK8: Protein
- SF3B1: Protein
- PD-1: Protein
- Ki-67: Protein
- FBP1: Protein
- HLA-DR: Protein
- eIF1A: Protein
- CD3: Protein
- FAP: Protein
- c-MYC: Protein
- CD29: Protein
- HMGCR: Protein
- ACC: Protein
- Pan-cytokeratin: Protein
- aSMA: Protein
- BRCA1: Protein
- Vimentin: Protein
File: ADT01.tar.gz
Description: Single-cell RNA sequencing files of a sample from a prostate cancer patient receiving neoadjuvant ADT, which are sequenced with the SeekOne DD platform and generated from the SeekSoulTools pipeline: matrix.mtx.gz, features.tsv.gz, and barcodes.tsv.gz. The expression levels are measured in counts.
File: ADT02.tar.gz
Description: Single-cell RNA sequencing files of a sample from a prostate cancer patient receiving neoadjuvant ADT, which are sequenced with the SeekOne DD platform and generated from the SeekSoulTools pipeline: matrix.mtx.gz, features.tsv.gz, and barcodes.tsv.gz. The expression levels are measured in counts.
File: ADT03.tar.gz
Description: Single-cell RNA sequencing files of a sample from a prostate cancer patient receiving neoadjuvant ADT, which are sequenced with the SeekOne DD platform and generated from the SeekSoulTools pipeline: matrix.mtx.gz, features.tsv.gz, and barcodes.tsv.gz. The expression levels are measured in counts.
File: ADT04.tar.gz
Description: Single-cell RNA sequencing files of a sample from a prostate cancer patient receiving neoadjuvant ADT, which are sequenced with the SeekOne DD platform and generated from the SeekSoulTools pipeline: matrix.mtx.gz, features.tsv.gz, and barcodes.tsv.gz. The expression levels are measured in counts.
File: HHT-01.tar.gz
Description: Single-cell RNA sequencing files of a sample from a prostate cancer patient receiving neoadjuvant HHT+ADT therapy, which are sequenced with the SeekOne DD platform and generated from the SeekSoulTools pipeline: matrix.mtx.gz, features.tsv.g,z and barcodes.tsv.gz. The expression levels are measured in counts.
File: HHT-02.tar.gz
Description: Single-cell RNA sequencing files of a sample from a prostate cancer patient receiving neoadjuvant HHT+ADT therapy, which are sequenced with the SeekOne DD platform and generated from the SeekSoulTools pipeline: matrix.mtx.gz, features.tsv.gz, and barcodes.tsv.gz. The expression levels are measured in counts.
File: HHT-03.tar.gz
Description: Single-cell RNA sequencing files of a sample from a prostate cancer patient receiving neoadjuvant HHT+ADT therapy, which are sequenced with the SeekOne DD platform and generated from the SeekSoulTools pipeline: matrix.mtx.gz, features.tsv.gz, and barcodes.tsv.gz. The expression levels are measured in counts.
File: HHT-04.tar.gz
Description: Single-cell RNA sequencing files of a sample from a prostate cancer patient receiving neoadjuvant HHT+ADT therapy, which are sequenced with the SeekOne DD platform and generated from the SeekSoulTools pipeline: matrix.mtx.gz, features.tsv.gz, and barcodes.tsv.gz. The expression levels are measured in counts.
File: Treatment_naive-01.tar.gz
Description: Single-cell RNA sequencing files of a sample from a treatment-naive patient with prostate cancer, which are sequenced with the SeekOne DD platform and generated from the SeekSoulTools pipeline: matrix.mtx.gz, features.tsv.gz, and barcodes.tsv.gz. The expression levels are measured in counts.
File: Treatment_naive-02.tar.gz
Description: Single-cell RNA sequencing files of a sample from a treatment-naive patient with prostate cancer, which are sequenced with the SeekOne DD platform and generated from the SeekSoulTools pipeline: matrix.mtx.gz, features.tsv.gz, and barcodes.tsv.gz. The expression levels are measured in counts.
File: Expression_matrix_FPKM_counts_myccap_HHT_ADT.txt
Description: The RNA-seq gene expression matrix of Myc-CaP subcutaneous tumors, among which three are from the HHT+ADT treatment group, and three are from the PBS control group. This matrix included expression values of genes both in counts and FPKM.
File: Expression_matrix_FPKM_counts_myccap_shEIF1A.txt
Description: The RNA-seq gene expression matrix of Myc-CaP subcutaneous tumors, among which three are from the sh-EIF1A treatment group, and three are from the sh-NC control group. This matrix included expression values of genes both in counts and FPKM.
File: Ribo-seq_RPF_and_mRNA_fpkm.txt
Description: The mRNA expression levels and ribosome-protected fragment (RPF) levels of genes derived from Ribosome profiling (Ribo-seq), among which two are from the sh-EIF1A treatment group, and two are from the sh-NC control group. The experiment was conducted in the 293T cell line. The levels are measured in FPKM.
Code/software
After unpacking, the scRNA-seq data can be loaded by the Seurat package in R with the "Read10X" function. Other matrices can be viewed as tables and be loaded in R through the "read.table" function.
Access information
Other publicly accessible locations of the data:
- No applicable.
Data was derived from the following sources:
- No applicable.