proteins involved in necroptosis and DNA damage repair and survival of stage I NSCLC patients

초록

Background: Survival of patients with stage I non-small-cell lung cancer (NSCLC) was indicative of significant variability with biological complexity. In addition to repairing DNA damage, understanding for necroptosis as new mechanism of cell death is rapidly growing as one of the hallmark of cancer. Therefore, the development of a prognostic biomarker focusing on necroptosis and DNA damage is an intriguing issue. Method: Expression of eight proteins (RIPK3, MLKL, PELI1, P53, ATM, gH2AX, Chk2, and BRCA1) and overall survival were investigated in 394 pathological stage I NSCLC patients. Result: The proteins involved in necroptosis or DNA damage repair exhibited differential expression between squamous cell carcinoma and other histology. Low expression of RIPK3 showed a trend for having worse survival in the entire cohort. Analysis performed based on histology revealed that expression of RIPK3, PELI1, P53, or BRCA1 was an independent prognostic factor in squamous cell carcinoma patients (aHR, Cox P: 2.292, 0.008 for RIPK3; 2.007, 0.033 for PELI1; 0.391, 0.003 for P53; 2.088, 0.018 for BRCA1). When combined effect of RIPK3 or PELI1 with P53 or DNA damage repair proteins analyzed, the effect on survival is was markedly strengthened in squamous cell carcinoma patients. However, these effects were not detected in adenocarcinoma patients. Conclusion: Expression or their combination of proteins involved in necroptosis and DNA damage repair is an important determinant of survival in stage I squamous cell carcinoma patients.