Evidence map›Paper›PMID 39604668›Full record

ArticleDigestive diseases and sciences2025

CD8 + T-Cell-Related Genes: Deciphering Their Role in the Pancreatic Adenocarcinoma TME and Their Effect on Prognosis.

Yuming Zhang, Helei Hou, Xuchen Zhang, Hongwei Lan, Xingfa Huo, Xueqin Duan, Yufeng Li, Xiaochun Zhang, Na Zhou

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Article in Digestive diseases and sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

9 authors.

Yuming ZhangPrecision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, No. 59 Haier Road, Qingdao, 266000, Shandong, China.
Helei HouDepartment of Oncology, The Affiliated Hospital of Qingdao University, No. 7 Jiaxing Road, Qingdao, 266000, Shandong, China.
Xuchen ZhangDepartment of Medicine, Qingdao University, No. 308 Ningxia Road, Qingdao, 266000, Shandong, China.
Hongwei LanPrecision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, No. 59 Haier Road, Qingdao, 266000, Shandong, China.
Xingfa HuoPrecision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, No. 59 Haier Road, Qingdao, 266000, Shandong, China.
Xueqin DuanPrecision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, No. 59 Haier Road, Qingdao, 266000, Shandong, China.
Yufeng LiDepartment of Medicine, Qingdao University, No. 308 Ningxia Road, Qingdao, 266000, Shandong, China.
Xiaochun ZhangPrecision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, No. 59 Haier Road, Qingdao, 266000, Shandong, China.
Na ZhouPrecision Medicine Center of Oncology, The Affiliated Hospital of Qingdao University, Qingdao University, No. 59 Haier Road, Qingdao, 266000, Shandong, China. zhouna@qdu.edu.cn.

Funding

Natural Science Foundation of Shandong Province ZR2022MH048
6 · The paper itself

Abstract

backgroundBecause of the unique tumor microenvironment (TME), immunotherapy and targeted therapies have shown limited efficacy in treating pancreatic adenocarcinoma (PAAD). CD8 + T cells play crucial roles in regulating the TME in PAAD; therefore, exploring the function of CD8 + T-cell-related genes (CD8RGs) in PAAD has high potential clinical value and could provide a comprehensive understanding of the microenvironment of PAAD.

methodsWe employed the weighted gene coexpression network analysis and CIBERSORT algorithms to assess PAAD transcriptome data from The Cancer Genome Atlas (TCGA) dataset and identify modules strongly associated with CD8 + T cell infiltration. Using least absolute shrinkage and selection operator regression analysis and Kaplan-Meier curves, we developed a prognostic risk score model for patients with PAAD. We validated this model using single-cell and transcriptome datasets obtained from the Gene Expression Omnibus (GEO). We also examined the correlations between the risk score and factors such as the TME, clinical characteristics, and tumor mutation burden (TMB). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed on differentially expressed genes between the high- and low-risk groups. In addition, the Tumor Immune Dysfunction and Exclusion website and "pRRophetic" R package were used to predict response to immunotherapy and chemotherapy in the high- and low-risk groups, respectively. Finally, we analyzed the expressions of hub genes at the cellular level with quantitative real-time PCR.

resultsA risk model based on five CD8RGs was established and validated using TCGA and GEO datasets. The low-risk group exhibited significantly longer overall and progression-free survival. A positive correlation between the TMB and the risk score was observed. The TME analysis revealed a significant correlation between the risk score and immune function, as well as immune checkpoints. The expression of hub genes was significantly correlated with the infiltration level of CD8 + T cells. The high-risk group responded better to immunotherapy, paclitaxel, cisplatin, mitomycin C, afatinib (BIBW2992), and gefitinib. In contrast, the low-risk group showed higher sensitivity to sunitinib, MK.2206, palbociclib (PD.0332991), and axitinib. Compared with that in normal pancreatic epithelial cells, the expression levels of BCL11A, PHOSPHO1, and GNG7 were significantly decreased, while those of KLK11 and VCAM1 were significantly increased in pancreatic tumor cells.

conclusionsCD8RGs play an important role in regulating the TME of PAAD. Five hub genes-BCL11A, KLK11, GNG7, PHOSPHO1, and VCAM1-are closely associated with the prognosis of PAAD patients, providing new references for the exploration of biomarkers. Furthermore, our findings offer novel insights for clinical decision-making.

Indexed as

AdenocarcinomaCD8-Positive T-LymphocytesPancreatic NeoplasmsTumor MicroenvironmentBiomarkers, TumorGene Expression ProfilingGene Expression Regulation, NeoplasticHumansPrognosisTranscriptomeBiomarkers, TumorCD8 + T cellsPancreatic adenocarcinomaPrognostic signatureTumor microenvironmentWeighted gene coexpression network analysis

Identifiers

PMID39604668

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.