Zhu Yaowu, Tan Li, Luo Danju, Wang Xiong
Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Infection Control, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Diagnostics (Basel). 2024 Mar 21;14(6):667. doi: 10.3390/diagnostics14060667.
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 (, , , , , and ) risk model was constructed. Patients with low risk had prolonged survival times in both the training (TCGA-PAAD, = 178) and validation (ICGC-PACA-CA, ICGC-PAAD-US, and GSE71729, = 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.
胰腺癌（PACA）是全球最致命的恶性肿瘤之一。免疫疗法对PACA患者大多无效。T细胞耗竭导致免疫疗法耐药。我们研究了T细胞耗竭相关基因（TEXGs）的预后潜力。
使用来自肿瘤免疫单细胞中心（TISCH）的单细胞RNA（scRNA）测序数据集以及来自癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）的批量测序数据集来筛选差异表达的TEXGs。进行Kaplan-Meier生存分析、LASSO回归分析和单变量/多变量Cox回归分析以构建TEXG风险模型。该模型用于预测预后、肿瘤免疫微环境和免疫疗法反应。使用来自ICGC和GSE71729数据集的PACA队列来验证风险模型。使用TISCH数据库确定SPOCK2在泛癌中的表达情况。
构建了一个六基因（、、、、和）风险模型。低风险患者在训练数据集（TCGA-PAAD， = 178）和验证数据集（ICGC-PACA-CA、ICGC-PAAD-US和GSE71729， = 412）中的生存时间均延长。多变量Cox回归分析表明，风险评分是PACA的独立预后变量。高风险患者与其免疫抑制状态相关。免疫组织化学染色证实了临床样本中TEXGs的变化。此外，来自TISCH分析的泛癌scRNA测序数据集表明，SPOCK2可能是耗竭的CD8 T细胞的新标志物。
我们为PACA患者建立并验证了一种与T细胞耗竭相关的预后特征。此外，我们的研究表明，SPOCK2是耗竭的CD8+ T细胞的新标志物。
