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Identification of the molecular subtype and prognostic characteristics of pancreatic cancer based on CD8 + T cell-related genes

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Abstract

CD8 + T lymphocytes are immune cells that play a crucial anti-tumor role in the human body, and prognostic value of CD8 + T cell-related regulatory genes in PAAD remains elusive. Data on 179 expression profiles across 13 immune cell datasets were downloaded from the GEO database, and the expression profiles of CD8 + T cell-related genes were obtained using WGCNA. Molecular subtypes based on CD8 + T cell-related genes were constructed using the ConsensusClusterPlus algorithm. Lasso regression analysis was performed to build a 10-gene signature. GSVA was performed to explore the pathways related to these ten genes. The IMvigor210 cohort was used to explore the predictive efficacy of the signature in terms of immunotherapy response. Four hundred and forty-six CD8 + T cell-related genes were obtained. One hundred and nine genes in TCGA and GEO datasets were closely related to the prognosis of patients and were included in the next study. PAAD samples were divided into two subtypes (IC1 and IC2) according to consensus cluster analysis. These two immune subtypes were significantly different in terms of immune checkpoint genes, immune function, and drug treatment response. Additionally, the 10-gene signature constructed based on CD8 + T cell-related genes showed a stable prognostic performance in TCGA and GEO cohorts. Moreover, it served as an independent prognostic factor for patients with PAAD. Furthermore, the 10-gene signature could effectively predict the response to immunotherapy. The immunophenotyping-derived prognostic model based on CD8 T cell-related genes provides a basis for the clinical treatment of pancreatic cancer.

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Availability of data and materials

The data used to support the findings of this study are available from the corresponding author on reasonable request.

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Abbreviations

PAAD:

Pancreatic adenocarcinoma

GEO:

Gene expression omnibus

WGCNA:

Weighted correlation network analysis

TCGA:

The cancer genome Atlas

GSVA:

Gene set variation analysis

TME:

Tumor microenvironment

CYT:

Cytolytic activity

AIC:

Akaike information criterion

GSEA:

Gene set enrichment analysis

NEO:

Neo-antigen

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Acknowledgements

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Funding

This study was funded by Natural Science Foundation of Hainan Province (820MS130); Hainan Provincial Science and Technology Program (Clinical Medical Research Center): LCYX202101.

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Authors and Affiliations

  1. Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China

    Dafeng Xu, Yonghai Chen & Jinfang Zheng

  2. Geriatric Medicine Center, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China

    Yu Wang

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  1. Dafeng Xu
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  2. Yu Wang
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  3. Yonghai Chen
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  4. Jinfang Zheng
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WY and XDF designed the study, performed data analysis, and wrote the manuscript. CYH performed data collection, and ZJF supervised the manuscript. The current manuscript has been read and approved by all named authors.

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Correspondence to Jinfang Zheng.

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Xu, D., Wang, Y., Chen, Y. et al. Identification of the molecular subtype and prognostic characteristics of pancreatic cancer based on CD8 + T cell-related genes. Cancer Immunol Immunother 72, 647–664 (2023). https://doi.org/10.1007/s00262-022-03269-3

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