KCTD9 expression predicts immunotherapy response and enhances anti-PD-1 efficacy in colon adenocarcinoma.

Purpose: Colon adenocarcinoma (COAD) is a commonly diagnosed malignancy in the world. While immunotherapy, specifically PD-1/PD-L1, shows potential as a treatment for COAD, its efficacy is limited to a minority of patients. This study sought to explore new biomarker that could predict the response to anti-PD-1/PD-L1 therapies in COAD.

Methods: In this study, KCTD9 was validated as a novel biomarker for predicting immunotherapy efficacy in colon cancer through transcriptomic expression analysis, cellular pathway activity analysis, immune infiltration analysis, and in vivo mouse xenograft tumor formation assays.

Results: Our findings revealed that KCTD9 was correlated with prognosis across multiple cancer types, and as a protective factor, the expression level of KCTD9 exhibited the most significant impact on colon cancer. Furthermore, positive correlations between KCTD9 expression and both microsatellite instability (MSI) and tumor mutational burden (TMB) were observed across multiple tumor types, with the strongest correlations being identified in colon cancer. Finally, high expression of KCTD9 was positively correlated with CD8+ T cell infiltration and CD8-positive α-β T cell activation pathway activity, and significantly enhanced the anti-tumor efficacy of PD-1 inhibitor.

Conclusions: Our data validated the strong association between KCTD9 expression and colon cancer prognosis, as well as its capacity to enhance immunotherapy efficacy, indicating that KCTD9 may represent a promising biomarker for colon cancer.