Downregulated STAT3 and STAT5B are prognostic biomarkers for colorectal cancer and are associated with immune infiltration.

Abstract

Background: Colorectal cancer has high incidence and mortality rates. The signal transducer and activator of transcription (STAT) family plays vital roles in the tumorigenesis and development of colorectal cancer. The expression, prognostic value, and immune function of the STAT family are becoming much more clearly.

Methods: Our study collected data from several public data portals such as TCGA (644 samples) and GTEx database (308 samples) and clinical samples (30 samples, China). Then we systematically assessed the expression level and prognostic value of the STAT family in colorectal cancer samples. Moreover, the immune function and immune infiltration levels of prognosis-related STAT members were explored via single cell RNA-seq and spatial transcriptomics technology data. Several useful portals and tools have been utilized such as CancerSEA and TISIDB in single-cell analysis, CBio Cancer Genomics in multidimensional alterations, MethSurv in DNA methylation, and related R packages.

Results: Our study found that STAT3 and STAT5B were significantly lower in colorectal cancer via multi-omics (P < 0.001). Higher STAT3 and STAT5B level were correlated with better future outcome. Nomograms were developed to predict the distal survival time (C-index = 0.724). The functions of STAT3 and STAT5B are associated with inflammation, the JAK/STAT pathway and the immune response. The major cell types of colorectal cancer were CD4Tconv, CD8T, CD8Tex, Tprolif, Treg and STAT3 and STAT5B widely expressed in these cells. STAT3 and STAT5B both correlated with CD244 and KDR for immune checkpoints.

Conclusion: STAT3 and STAT5B are downregulated in colorectal cancer and have great potential as prognostic biomarkers and novel immunotherapy targets.