DOI: 10.5061/dryad.tqjq2bwb3
title: A unified eIF1A<sup>+</sup> luminal cells-centered hypoxic and “cold” tumor microenvironment promotes PCa progression among different subtypes

description: 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.
description: # A unified eIF1A ^+^ luminal cells-centered hypoxic and “cold” tumor
 microenvironment promotes PCa progression among different subtypes Dataset
 DOI: [10.5061/dryad.tqjq2bwb3](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.