Abstract
Background
High tumor mutation burden (TMB) failed to serve as a favorable prognostic biomarker for immunotherapy across all tumors. This study aimed to explore TMB-sensitive tumors on a pan-cancer level and construct their immune infiltration phenotypes in TMB-high groups.
Methods
Pan-cancer patients were separated into TMB-high and TMB-low groups based on the median TMB values per tumor. TMB-related genes were identified using differently expressed genes (DEGs) and differently mutated genes (DMGs) between the above two TMB groups. CIBERSORT algorithm was used to estimate the abundance of 22 tumor immune infiltrating cells (TIICs). Consensus clustering analysis was applied to predict molecular subtypes. Cox regression analysis was performed to evaluate the correlations between hub genes and TIICs and immunomodulator genes.
Results
Nine TMB-sensitive tumors were identified by high-frequency of TMB-related genes. A total of 126 tumor-specific hub genes (1 in BLCA, 19 in BRCA, 4 in COAD, 4 in HNSC, 25 in LUAD, 2 in LUSC, 27 in SKCM, 37 in STAD, and 7 UCEC) were identified. In five out of nine TMB-sensitive tumors, the molecular subtypes based on hub gene expression were characterized by TMB values, prognostic values and tumor-specific TIICs levels. In TMB-high groups, hub genes associated immune infiltration phenotypes were constructed with key TIICs and immunomodulators spanning TMB-sensitive tumors.
Conclusions
Our tumor-specific analysis revealed hub genes associated immune infiltration features may serve as potential therapeutic targets and prognostic markers of immunotherapy, providing the potential underlying mechanism of immune infiltration in TMB-high groups across TMB-sensitive tumors.
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Data availability
Data are available in a public, open access repository. The data sets analyzed during the current study are available in The Cancer Genome Atlas (TCGA) (http://gdac.broadinstitute.org).
Abbreviations
- BLCA:
-
Bladder urothelial carcinoma
- BRCA:
-
Breast invasive carcinoma
- COAD:
-
Colon adenocarcinoma
- ESCA:
-
Esophageal carcinoma
- HNSC:
-
Head and neck squamous cell carcinoma
- KIRC:
-
Kidney renal clear cell carcinoma
- LGG:
-
Brain lower grade glioma
- LIHC:
-
Liver hepatocellular carcinoma
- LUAD:
-
Lung adenocarcinoma
- LUSC:
-
Lung squamous cell carcinoma
- OV:
-
Ovarian serous cystadenocarcinoma
- PAAD:
-
Pancreatic adenocarcinoma
- PRAD:
-
Prostate adenocarcinoma
- SKCM:
-
Skin cutaneous melanoma
- STAD:
-
Stomach adenocarcinoma
- THYM:
-
Thymoma
- UCEC:
-
Uterine corpus endometrial carcinoma
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Acknowledgements
We sincerely acknowledge the contributions from the TCGA project.
Funding
This work was supported by the National Natural Science Foundation of China (82073284); Shenzhen Key Medical Discipline Construction Fund (SZXK053); Guangdong Basic and Applied Basic Research Foundation (2021A1515012163).
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HuW and YC conceptualized and designed the study. All authors wrote the manuscript; HuW and HaW collected and analyzed the data. All authors read and approved the final manuscript.
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Wu, H., Wang, H. & Chen, Y. Pan-cancer analysis of tumor mutation burden sensitive tumors reveals tumor-specific subtypes and hub genes related to immune infiltration. J Cancer Res Clin Oncol 149, 2793–2804 (2023). https://doi.org/10.1007/s00432-022-04139-2
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DOI: https://doi.org/10.1007/s00432-022-04139-2