Predicting survival and immune microenvironment in colorectal cancer: a STAT signaling-related signature

Abstract

Background: Despite research advances, studies on predictive models of colorectal cancer (CRC) remain scarce and none have evaluated signal transducer and activator of transcription (STAT) signaling.

Aim: To develop an effective prognostic signature for and evaluate its association with immune microenvironment.

Design: Comprehensive analysis based on The Cancer Genome Atlas and Gene Expression Omnibus databases with experimental validation.

Methods: Gene expression and clinical profiles of CRC patients were extracted from the databases. Differentially expressed genes with prognostic values were used to construct a signature. Immune cell infiltration and composition were further evaluated by TIMER, single-sample gene set enrichment and CIBERSORT analyses. The impact of the hub gene Caveolin-1 (CAV1) on cell proliferation, apoptosis, senescence and tumor angiogenesis was experimentally validated.

Results: The five-gene-based STAT signaling-related prognostic signature was significantly associated with CRC survival, and the nomogram was with improved prognostic efficacy than the conventional TNM stage. The STAT signaling-related signature was correlated with tumor immune microenvironment. CAV1 was further identified as the hub gene within the signature. CAV1 inhibits the proliferation and induces the apoptosis as well as senescence of CRC cells. In addition, the tumor angiogenesis of CRC can be suppressed by CAV1 overexpression.

Conclusions: The STAT signaling-related signature effectively predicts the prognosis and regulates tumor immune microenvironment in CRC. Our study underscores the role of STAT regulator, CAV1, as an important tumor suppressor in CRC carcinogenesis. Modulating STAT and its regulators could be a promising strategy for CRC in clinical practice.