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Comprehensive pan-cancer analysis reveals prognostic implications of TMEM92 in the tumor immune microenvironment

  • RESEARCH ARTICLE
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Abstract

Background

Transmembrane protein 92 (TMEM92) has been implicated in the facilitation of tumor progression. Nevertheless, comprehensive analyses concerning the prognostic significance of TMEM92, as well as its role in immunological responses across diverse cancer types, remain to be elucidated.

Methods

In this study, data was sourced from a range of publicly accessible online platforms and databases, including TCGA, GTEx, UCSC Xena, CCLE, cBioPortal, HPA, TIMER2.0, GEPIA, CancerSEA, GDSC, exoRBase, and ImmuCellAI. We systematically analyzed the expression patterns of TMEM92 at both mRNA and protein levels across diverse human organs, tissues, extracellular vesicles (EVs), and cell lines associated with multiple cancer types. Subsequently, analyses were conducted to determine the relationship between TMEM92 and various parameters such as prognosis, DNA methylation, copy number variation (CNV), the tumor microenvironment (TME), immune cell infiltration, genes with immunological relevance, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and half-maximal inhibitory concentration (IC50) values.

Results

In the present study, we observed a pronounced overexpression of TMEM92 across a majority of cancer types, which was concomitantly associated with a less favorable prognosis. A notable association emerged between TMEM92 expression and both DNA methylation and CNV. Furthermore, a pronounced relationship was discerned between TMEM92 expression, the TME, and the degree of immune cell infiltration. Intriguingly, while TMEM92 expression displayed a positive correlation with macrophage presence, it inversely correlated with the infiltration level of CD8 +  T cells. Concurrently, significant associations were identified between TMEM92 and the major histocompatibility complex, TMB, MSI, and MMR. Results derived from Gene Set Enrichment Analysis and Gene Set Variation Analysis further substantiated the nexus of TMEM92 with both immune and metabolic pathways within the oncogenic context.

Conclusions

These findings expanded the understanding of the roles of TMEM92 in tumorigenesis and progression and suggest that TMEM92 may have an immunoregulatory role in several malignancies.

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Data availability

All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.

Abbreviations

ACC:

Adrenocortical carcinoma

BLCA:

Bladder urothelial carcinoma

BRCA:

Breast invasive carcinoma

CESC:

Cervical squamous cell carcinoma and endocervical adenocarcinoma

CHOL:

Cholangio carcinoma

COAD:

Colon adenocarcinoma

DLBC:

Lymphoid neoplasm diffuse large B-cell lymphoma

ESCA:

Esophageal carcinoma

ESCC:

Esophageal squamous cell carcinoma

GBM:

Glioblastoma multiforme

HNSC:

Head and neck squamous cell carcinoma

KICH:

Kidney chromophobe

KIRC:

Kidney renal clear cell carcinoma

KIRP:

Kidney renal papillary cell carcinoma

LAML:

Acute myeloid leukemia

LGG:

Brain lower grade glioma

LIHC:

Liver hepatocellular carcinoma

LUAD:

Lung adenocarcinoma

LUSC:

Lung squamous cell carcinoma

MEL:

Melanoma

MESO:

Mesothelioma

OV:

Ovarian serous cystadenocarcinoma

PAAD:

Pancreatic adenocarcinoma

PCPG:

Pheochromocytoma and paraganglioma

PRAD:

Prostate adenocarcinoma

READ:

Rectum adenocarcinoma

SKCM:

Skin cutaneous melanoma

TGCT:

Testicular germ cell tumors

THCA:

Thyroid carcinoma

THYM:

Thymoma

UCEC:

Uterine corpus endometrial carcinoma

UCS:

Uterine carcinosarcoma

UVM:

Uveal melanoma

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Acknowledgements

We would like to acknowledge the hard and dedicated work of all the staff that implemented the intervention and evaluation components of the study.

Funding

This study was funded by Natural Science Foundation of Hebei Province (No. H2022206221) Medical science research project of Hebei Province (No. 20240095)

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Authors and Affiliations

  1. Department of Immuno-Oncology, The Fourth Hospital of Hebei Medical University, No. 12 of Jiankang Road, Chang-an District, Shijiazhuang, 050011, Hebei, China

    Zheng Wu, Teng Pan, Wen Li, Yue-hua Zhang, Sheng-hu Guo, Ya Liu, Lei Zhang & Zhi-yu Wang

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  1. Zheng Wu
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Contributions

Conception and design of the research: Wu Z, Wang ZY. Acquisition of data: Zhang YH, Guo SH, Liu Y. Analysis and interpretation of the data: Liu Y, Zhang L, Li W. Statistical analysis: Guo SH, Liu Y. Obtaining financing: Wu Z. Writing of the manuscript: Wu Z, Pan T. Critical revision of the manuscript for intellectual content: Li W, Zhang YH, Wang ZY. All authors read and approved the final draft.

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Correspondence to Zhi-yu Wang.

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Wu, Z., Pan, T., Li, W. et al. Comprehensive pan-cancer analysis reveals prognostic implications of TMEM92 in the tumor immune microenvironment. Clin Transl Oncol (2024). https://doi.org/10.1007/s12094-024-03477-6

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