CLDN4 as Pan-Cancer Prognostic Marker and its Effects on Immune Infiltration in the Tumor Microenvironment

Authors

  • Yi Xu Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
  • Yihui Gu Department of Gynecology, The First People's Hospital of Lianyungang, Jiangsu, China
  • Yang Shen, M.D., Ph.D Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
  • Wen Feng, MD Department of Gynecology, The First People's Hospital of Lianyungang, Lianyungang, 222000, Jiangsu Province, China, China

Keywords:

Pan-cancer, Prognostic marker, Immune infiltration, Target

Abstract

Background: CLDN4, a member of tight junction protein, whose abnormal expression will lead to dysregulated differentiation and polarity in tumors. This research aims to explore the effect of CLDN4 expression on staging and prognosis in pan-cancer, and the relationship between CLDN4 expression in immune infiltration microenvironment and immunomodulatory genes.

Methods: We downloaded RNA-seq expression datasets from TCGA and GTEx databases to analyze the datasets of CLDN4. HPA, gene card, and string database were used to investigate the degree of CLDN4 protein expression and subcellular localization. The clinical survival data of TCGA were used to explore the staging relationship and influence on prognosis. CLDN4 was enriched and analysed. Finally, the correlation between CLDN4 and cell infiltration in tumor immune microenvironment in TCGA pan-cancer samples was analyzed, and the expression of CLDN4 was scored with stromal cells and immune cell infiltration degrees. The relationship between CLDN4 and chemokine, receptor, MHC, immune inhibitor, and immune stimulator was further evaluated.

Results: We found that CLDN4 is at a high level of expression in most cancer types, and it is highly expressed in the advanced stage of most cancer types, which is different from the prognosis of different cancer types and mostly negatively correlated. The expression of CLDN4 is obviously related to TMB and MSI, and further research shows that it is negatively related to most tumor-infiltrating immune cells. For example, all cancer types are negatively related to native CD8+T cells, and CLDN4 is related chiefly to the immune regulator gene.

Conclusion: The final conclusion is that the expression of the CLDN4 gene plays a role in the occurrence, invasion, and tumor immune cell infiltration of most tumors, which can not only be used as a marker of prognosis but also provide a target for tumor immunotherapy.

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Published

2024-02-20

Issue

Section

Original Articles

How to Cite

Yi Xu, Yihui Gu, Yang Shen, M.D., Ph.D, and Wen Feng, MD , trans. 2024. “CLDN4 As Pan-Cancer Prognostic Marker and Its Effects on Immune Infiltration in the Tumor Microenvironment”. Human Biology 94 (1): 406-15. https://www.humbiol.org/Home/article/view/21.