IL4I1: a novel molecular biomarker represents an inflamed tumor microenvironment and precisely predicts the molecular subtype and immunotherapy response of bladder cancer

IL4I1:一种新型分子生物标志物,代表发炎的肿瘤微环境,可准确预测膀胱癌的分子亚型和免疫治疗反应

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作者:Xiangrong Peng #, Chuan Liu #, Li Zhang #, Yin Chen, Lixin Mao, Shenglin Gao, Xiaokai Shi, Li Zuo

Discussion

To summarize, our research showed that elevated IL4I1 levels are indicative of an inflamed TME, the basal subtype, and a more favorable response to various treatment methods, especially immune checkpoint blockade therapy in BLCA.

Methods

We analyzed RNA sequencing data from the Cancer Genome Atlas (TCGA) to investigate the immune function and prognostic importance of IL4I1 across different cancer types. We further examined the TCGA-BLCA cohort for correlations between IL4I1 and various immunological characteristics of tumor microenvironment (TME), such as cancer immune cycle, immune cell infiltration, immune checkpoint expression and T cell inflamed score. Validation was conducted using two independent cohort, GSE48075 and E-MTAB-4321. Finally, RNA sequencing data from the IMvigor210 cohort and immunohistochemistry assays were employed to validate the predictive value of IL4I1 for the TME and immunotherapy efficacy.

Results

In our findings, a positive correlation was observed between IL4I1 expression and immunomodulators expression, immune cell infiltration, the cancer immune cycle, and T cell inflamed score in BLCA, suggesting a significant link to the inflamed TME. In addition, studies have shown that IL4I1 elevated levels of individuals tend to be more performance for basal subtype and exhibit enhanced response rates to diverse treatment modalities, specifically immunotherapy. Clinical data from the IMvigor 210 cohort confirmed a higher rate of response to immunotherapy and better survival benefits in patients with high IL4I1 expression.

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