Identifying survival of pan-cancer patients under immunotherapy using genomic mutation signature with large sample cohorts.

Abstract

Although immune checkpoint inhibitors have led to durable clinical response in multiple cancers, only a small proportion of patients respond to this treatment. Therefore, we aim to develop a predictive model that utilizes gene mutation profiles to accurately identify the survival of pan-cancer patients with immunotherapy. Here, we develop and evaluate three different nomograms using two cohorts containing 1,594 cancer patients whose mutation profiles are obtained by MSK-IMPACT sequencing and 230 cancer patients receiving whole-exome sequencing, respectively. Using eighteen genes (SETD2, BRAF, NCOA3, LATS1, IL7R, CREBBP, TET1, EPHA7, KDM5C, MET, KMT2D, RET, PAK7, CSF1R, JAK2, FAT1, ASXL1 and SPEN), the first nomogram stratifies patients from both cohorts into High-Risk and Low-Risk groups. Pan-cancer patients in the High-Risk group exhibit significantly shorter overall survival and progression-free survival than patients in the Low-Risk group in both cohorts. Meanwhile, the first nomogram also accurately identifies the survival of patients with melanoma or lung cancer undergoing immunotherapy, or pan-cancer patients treated with anti-PD-1/PD-L1 inhibitor or anti-CTLA-4 inhibitor. The model proposed is not a prognostic model for the survival of pan-cancer patients without immunotherapy, but a simple, effective and robust predictive model for pan-cancer patients' survival under immunotherapy, and could provide valuable assistance for clinical practice.