Identification and validation of a ferroptosis-related prognostic risk-scoring model and key genes in small cell lung cancer

作者：Suyang Li, Guihuan Qiu, Wu Jun, Jiaxin Ying, Haiyi Deng, Xiaohong Xie, Xinqing Lin, Zhanhong Xie, Yinyin Qin, Yansheng Wang, Xiaodong Ma, Luka Brčić, Mariano Provencio, Yangchao Chen, Chengzhi Zhou, Ming Liu · 发表于：Translational Lung Cancer Research · 年份：2022 · DOI：10.21037/tlcr-22-408 · 被引用次数：10 · 研究领域：Ferroptosis and cancer prognosis、Lung Cancer Research Studies、Clusterin in disease pathology

Background: Small cell lung cancer (SCLC) is an aggressive lung malignancy with high relapse rates and poor survival outcomes. Ferroptosis is a recently identified type of cell death caused by excessive intracellular iron accumulation and lipid peroxidation, which may mediate tumor-infiltrating immune cells to influence anti-cancer immunity. But prognostic value of ferroptosis-related genes and its relationship with the treatment response of immunotherapies in SCLC have not been elucidated. Methods: The RNA-sequencing and clinical data of SCLC patients were downloaded from the cBioPortal database. A ferroptosis-related prognostic risk-scoring model was constructed based on univariable and multivariable Cox-regression analysis. Kaplan-Meier (K-M) survival curves and receiver operating characteristics (ROC) curves were constructed to assess the sensitivity and specificity of the risk-scoring model. And the correlations between ferroptosis-related prognostic genes and immune microenvironment were explored. The IC50 values of anti-cancer drugs were downloaded from the Genomics of Drug Sensitivity in Cancer (GDSC) database and the correlation analysis with the key gene thioredoxin-interacting protein (TXNIP) was performed. In addition, immunohistochemistry (IHC) staining was employed to detect the expression of TXNIP in 20 SCLC patients who received first-line chemo-immunotherapy. Immunotherapeutic response according to iRECIST (Response Evaluation Criteria in Solid Tumours for im...