Identification and Validation of T-Cell Exhaustion Signature for Predicting Prognosis and Immune Response in Pancreatic Cancer by Integrated Analysis of Single-Cell and Bulk RNA Sequencing Data
单位：[1]Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.检验科华中科技大学同济医学院附属同济医院[2]Department of Infection Control, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.感染科华中科技大学同济医学院附属同济医院[3]Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.华中科技大学同济医学院附属协和医院
Pancreatic cancer (PACA) is one of the most fatal malignancies worldwide. Immunotherapy is largely ineffective in patients with PACA. T-cell exhaustion contributes to immunotherapy resistance. We investigated the prognostic potential of T-cell exhaustion-related genes (TEXGs).A single-cell RNA (scRNA) sequencing dataset from Tumor Immune Single-Cell Hub (TISCH) and bulk sequencing datasets from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) were used to screen differentially expressed TEXGs. Kaplan-Meier survival, LASSO regression, and univariate/multivariate Cox regression analyses were performed to construct a TEXG risk model. This model was used to predict the prognosis, tumor immune microenvironment, and immunotherapy response. The PACA cohorts from the ICGC and GSE71729 datasets were used to validate the risk model. Pan-cancer expression of SPOCK2 was determined using the TISCH database.A six-gene (SPOCK2, MT1X, LIPH, RARRES3, EMP1, and MEG3) risk model was constructed. Patients with low risk had prolonged survival times in both the training (TCGA-PAAD, n = 178) and validation (ICGC-PACA-CA, ICGC-PAAD-US, and GSE71729, n = 412) datasets. Multivariate Cox regression analysis demonstrated that the risk score was an independent prognostic variable for PACA. High-risk patients correlated with their immunosuppressive status. Immunohistochemical staining confirmed the changes in TEXGs in clinical samples. Moreover, pan-cancer scRNA sequencing datasets from TISCH analysis indicated that SPOCK2 may be a novel marker of exhausted CD8+ T-cells.We established and validated a T-cell exhaustion-related prognostic signature for patients with PACA. Moreover, our study suggests that SPOCK2 is a novel marker of exhausted CD8+ T cells.
基金：
Tongji Hospital: Tongji Medical College, Huazhong University of Science and Technology
provided funding for this work (2021141 to X.W.).
第一作者单位：[1]Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Zhu Yaowu,Tan Li,Luo Danju,et al.Identification and Validation of T-Cell Exhaustion Signature for Predicting Prognosis and Immune Response in Pancreatic Cancer by Integrated Analysis of Single-Cell and Bulk RNA Sequencing Data[J].DIAGNOSTICS.2024,14(6):doi:10.3390/diagnostics14060667.
APA：
Zhu Yaowu,Tan Li,Luo Danju&Wang Xiong.(2024).Identification and Validation of T-Cell Exhaustion Signature for Predicting Prognosis and Immune Response in Pancreatic Cancer by Integrated Analysis of Single-Cell and Bulk RNA Sequencing Data.DIAGNOSTICS,14,(6)
MLA：
Zhu Yaowu,et al."Identification and Validation of T-Cell Exhaustion Signature for Predicting Prognosis and Immune Response in Pancreatic Cancer by Integrated Analysis of Single-Cell and Bulk RNA Sequencing Data".DIAGNOSTICS 14..6(2024)
