SDH mutations, as potential predictor of chemotherapy prognosis in small cell lung cancer patients

Author:

Zeng Ran,Fan Xiaoyun,Yang Jin,Fang Chen,Li Jieyi,Wen Wei,Liu Jing,Lv Mengchen,Feng Xiangran,Zhao XiaoKai,Yu Hongjie,Zhang Yuhuan,Sun Xianwen,Bao Zhiyao,Zhou Jun,Ni Lei,Wang Xiaofei,Cheng Qijian,Gao Beili,Gong Ziying,Zhang Daoyun,Dong Yuchao,Xiang Yi

Abstract

Abstract Purpose Small cell lung cancer (SCLC) is an aggressive and rapidly progressive malignant tumor characterized by a poor prognosis. Chemotherapy remains the primary treatment in clinical practice; however, reliable biomarkers for predicting chemotherapy outcomes are scarce. Methods In this study, 78 SCLC patients were stratified into “good” or “poor” prognosis cohorts based on their overall survival (OS) following surgery and chemotherapeutic treatment. Next-generation sequencing was employed to analyze the mutation status of 315 tumorigenesis-associated genes in tumor tissues obtained from the patients. The random forest (RF) method, validated by the support vector machine (SVM), was utilized to identify single nucleotide mutations (SNVs) with predictive power. To verify the prognosis effect of SNVs, samples from the cbioportal database were utilized. Results The SVM and RF methods confirmed that 20 genes positively contributed to prognosis prediction, displaying an area under the validation curve with a value of 0.89. In the corresponding OS analysis, all patients with SDH, STAT3 and PDCD1LG2 mutations were in the poor prognosis cohort (15/15, 100%). Analysis of public databases further confirms that SDH mutations are significantly associated with worse OS. Conclusion Our results provide a potential stratification of chemotherapy prognosis in SCLC patients, and have certain guiding significance for subsequent precise targeted therapy.

Funder

Key Research and Development Program of Zhejiang province

Zhejiang Leading Talent Entrepreneurship Project

National Key Research and Development Program of China

Shanghai Key Discipline for Respiratory Diseases

National Natural Science Foundation of China

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Endocrine and Autonomic Systems,Endocrinology,Oncology,Endocrinology, Diabetes and Metabolism

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