Overexpression of MTHFD2 represents an inflamed tumor microenvironment and precisely predicts the molecular subtype and immunotherapy response of bladder cancer

MTHFD2 的过度表达代表发炎的肿瘤微环境,并精确预测膀胱癌的分子亚型和免疫治疗反应

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作者:Xiaokai Shi #, Xiangrong Peng #, Yin Chen #, Zebin Shi, Chuang Yue, Li Zuo, Lifeng Zhang, Shenglin Gao

Conclusion

Collectively, high MTHFD2 predicts an inflamed TME, a basal-like subtype, and a better response to various therapeutic strategies, especially the ICB therapy, in bladder cancer.

Methods

RNA sequencing data from The Cancer Genome Atlas (TCGA) was applied to analyze the immunological roles and prognostic value of MTHFD2 in pan-cancers. The association of MTHFD2 with several immunological features of tumor microenvironment (TME), including cancer-immunity cycle, immune cells infiltration, immune checkpoints expression, and T cell inflamed score was analyzed in TCGA-BLCA cohort. The predictors of cancer treatments effectiveness, including the expression and mutation of certain genes, molecular subtypes, and several signatures were evaluated as well. These

Results

MTHFD2 was found to be positively associated with several immunological features of an inflamed tumor microenvironment (TME) in various cancers and could predict BLCA patients' prognosis. In BLCA, high expression of MTHFD2 was observed to be positively related with the cancer-immunity cycle, the infiltration of several immune cells, and the expression of immunoregulators and T-cell inflamed scores, indicating a positive correlation with the inflamed TME. Moreover, patients with high MTHFD2 expression were more likely to be basal-like subtypes and respond to BLCA treatments, including immunotherapy, chemotherapy, and target therapy. The clinical data of the IMvigor210 cohort confirmed the higher response rates and better survival benefits of immunotherapy in high-MTHFD2-expression patients.

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