Zhang Shirong, Xiao Xiao, Zhu Xiuli, Chen Xueqin, Zhang Xiaochen, Xiang Jingjing, Xu Rujun, Shao Zhuo, Bai Jing, Xun Yanping, Jiang Yanping, Chen Zhengzheng, Xia Xuefeng, Jiang Hong, Ma Shenglin
Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Cancer Center, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
Translational Medicine Research Center, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
Cancers (Basel). 2022 Jun 22;14(13):3061. doi: 10.3390/cancers14133061.
The underlying mechanism of post-operative relapse of non-small cell lung cancer (NSCLC) remains poorly understood. We enrolled 57 stage I NSCLC patients with or without relapse and performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) on available primary and recurrent tumors, as well as on matched tumor-adjacent tissues (TATs). The WES analysis revealed that primary tumors from patients with relapse were enriched with mutation and 2q31.1 amplification. RNA-seq data showed that the relapse risk was associated with aberrant immune response and metabolism in the microenvironment of primary lesions. TATs from the patients with relapse showed an immunosuppression state. Moreover, recurrent lesions exhibited downregulated immune response compared with their paired primary tumors. Genomic and transcriptomic features were further subjected to build a prediction model classifying patients into groups with different relapse risks. We show that the recurrence risk of stage I NSCLC could be ascribed to the altered immune and metabolic microenvironment. TATs might be affected by cancer cells and facilitate the invasion of tumors. The immune microenvironment in the recurrent lesions is suppressed. Patients with a high risk of relapse need active post-operative intervention.
非小细胞肺癌（NSCLC）术后复发的潜在机制仍知之甚少。我们招募了57例有或无复发的I期NSCLC患者，对可用的原发性和复发性肿瘤以及匹配的肿瘤邻近组织（TAT）进行了全外显子组测序（WES）和RNA测序（RNA-seq）。WES分析显示，复发患者的原发性肿瘤富含突变和2q31.1扩增。RNA-seq数据表明，复发风险与原发性病变微环境中的异常免疫反应和代谢有关。复发患者的TAT呈现免疫抑制状态。此外，与配对的原发性肿瘤相比，复发性病变的免疫反应下调。进一步利用基因组和转录组特征构建预测模型，将患者分为具有不同复发风险的组。我们表明，I期NSCLC的复发风险可归因于免疫和代谢微环境的改变。TAT可能受癌细胞影响并促进肿瘤侵袭。复发性病变中的免疫微环境受到抑制。复发风险高的患者需要积极的术后干预。
