Abstract
Tumor necrosis factor (TNF) family members participate in the body's antitumor immunity response and influence tumor prognosis and treatment response. However, little is known about the roles of TNF family members in small cell lung cancer (SCLC). Therefore, we conducted the first comprehensive investigation of TNF family members in patients with SCLC, with the goal of using them to predict prognosis and chemotherapy benefit. Abnormal genetic alterations and expression of TNF family members were found to be widespread in SCLC patients. Using LASSO Cox regression analysis, we constructed a TNF family-based signature that separated SCLC patients in the training set (n=77) into high- and low-risk groups with distinct survival and chemotherapy benefit, and the signature was well-validated in the validation set (n=137) by RT-qPCR. Importantly, the signature exhibited superior predictive performance and was identified as a novel independent prognostic factor. Additionally, different immune phenotypes were found between the low-risk and high-risk groups, and high-risk patients had higher CMTM6 expression, suggesting that these patients could benefit from therapeutic methods targeting CMTM6. We constructed the first clinically applicable TNF family-based signature for predicting prognosis and chemotherapy benefit for patients with SCLC. The findings reported here provide a new method for predicting the prognosis of SCLC patients and optimizing clinical management.