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东亚人和高加索人之间小细胞肺癌的基因组和免疫特征

Genomic and immunological profiles of small-cell lung cancer between East Asians and Caucasian.

作者信息

Lin Anqi, Zhou Ningning, Zhu Weiliang, Zhang Jiexia, Wei Ting, Guo Linlang, Luo Peng, Zhang Jian

机构信息

Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, China.

Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.

出版信息

Cancer Cell Int. 2022 Apr 29;22(1):173. doi: 10.1186/s12935-022-02588-w.

Abstract

The characterization of immunological and genomic differences in small-cell lung cancer (SCLC) between East Asian (EA) and Caucasian patients can reveal important clinical therapies for EA patients with SCLC. By sequencing and analyzing a molecular and immunological dataset of 98-SCLC patients of EA ancestry, immunogenicity, including DNA damage repair alterations and tumor mutation burden (TMB), was found to be significantly higher in the EA cohort than in the Caucasian cohort. The epithelial-mesenchymal transition (EMT) was the signaling signature with the predominant frequency of mutations across all patients in the EA cohort. Analysis of tumor-infiltrated immune cells revealed that resting lymphocytes were significantly enriched in the EA cohort. Compound-targeting analysis showed that topoisomerase inhibitors might be capable of targeting TP53 and RB1 comutations in EA SCLC patients. EA SCLC patients who harbored COL6A6 mutations had poor survival, while Caucasian SCLC patients with OTOF, ANKRD30B, and TECPR2 mutations were identified to have a shorter survival.

摘要

对东亚(EA)和白种人小细胞肺癌(SCLC)患者免疫和基因组差异的特征分析,可为EA SCLC患者揭示重要的临床治疗方法。通过对98例EA血统SCLC患者的分子和免疫数据集进行测序和分析,发现EA队列中的免疫原性,包括DNA损伤修复改变和肿瘤突变负担(TMB),显著高于白种人队列。上皮-间质转化(EMT)是EA队列中所有患者突变频率占主导的信号特征。对肿瘤浸润免疫细胞的分析显示,静息淋巴细胞在EA队列中显著富集。复合靶点分析表明,拓扑异构酶抑制剂可能能够靶向EA SCLC患者中的TP53和RB1共突变。携带COL6A6突变的EA SCLC患者生存率较低,而携带OTOF、ANKRD30B和TECPR2突变的白种人SCLC患者被确定生存期较短。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af9a/9052616/6f69ad350586/12935_2022_2588_Fig1_HTML.jpg

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