摘要标题：一线标准化疗后，疾病进展(PD)和疾病缓解(PR)的小细胞肺癌患者基因谱的差异性分析

Background/Aim: Small-cell lung cancer (SCLC) is an aggressive lung tumor subtype with high malignancy, frequent metastases and poor prognosis. SCLC patients are relatively sensitive to radiotherapy and chemotherapy, which are mainly therapy in the clinical of SCLC. However, the puzzle in the therapy was the rapid resistance of tumor cells against chemotherapy and the failure of second-line chemotherapy. The purpose of this study was to use the accurate medical method to screen out the genes related to SCLC and the key molecular markers that are suitable for the curative effect of chemotherapy, resulting in realize the molecular prediction of small cell lung cancer. 

研究背景：小细胞肺癌(Small-cell lung cancer, SCLC)是一种极具侵袭性的肺癌亚型，具有恶性程度高、转移广泛、预后差等特征。由于SCLC患者对放化疗比较敏感，临床上的治疗主要以放化疗为主。然而，治疗中的问题关键是肿瘤细胞的快速耐药及二线化疗的失败。本研究的目的是利用精准医学的方法，筛选出与SCLC相关的基因，以及适合于化疗疗效的关键分子标志物，为实现小细胞肺癌的分子预测提供可能。

Patients and Methods: 24 patients with first-line treatment of SCLC receiving standard chemotherapy (EP) were included, whom were reviewed and categorized into two groups: disease progression (PD) and disease remission (PR). The tumor tissue DNA of the patients were detected by specific target gene capture sequencing technology to detect the gene variation of SCLC and bioinformatics methods were used to screen chemotherapy-related genes. 

研究方法：本研究对纳入的24例一线接受标准化疗方案(EP)治疗的SCLC患者进行回顾性研究，经疗效评价分为疾病进展（PD）和疾病缓解（PR）两组。采用特定的目标基因捕获测序技术检测患者肿瘤组织DNA中SCLC驱动基因变异情况，通过生物信息学方法分析筛选SCLC化疗疗效相关基因。

Results:TP53, CYP2C19, ZFHX3, BCL2 are the Common gene mutations in Chinese SCLC patient population; Common Genes for Copy number variations(CNV) in Small Cell Lung Cancer in China: FDPS,SOX2,MAP2K2,PSMA8,MALAT1; The comparative analysis in patients with CNV between PD and PR groups showed EGFR gene copy number variation was detected only in the PR group, and there was a significant difference between the two groups (P <0.05, Fisher test); The tumor tissue DNA somatic cells single nucleotide variants (SNV), genotypes associated with first-line chemotherapy(EP), Tumor Mutational Burden(TMB) and Copy number instability(CNI) of tumor tissues showed no significant difference between two groups.

研究结果：中国的小细胞肺癌人群发生的突变常见基因包括：TP53、CYP2C19、ZFHX3、BCL2等。中国小细胞肺癌人群发生拷贝数变异(CNV)的常见基因包括：FDPS、SOX2、MAP2K2、PSMA8、MALAT1等。PD组与PR组患者的CNV的人群比例对比分析，仅在PR组检测到EGFR基因拷贝数变异，且在两组间具有显著差异(P <0.05, Fisher 检验)。肿瘤组织DNA体细胞单核苷酸变异(SNV)、与EP一线化疗相关基因位点基因型、肿瘤突变负荷(TMB)和肿瘤组织拷贝数不稳定性(CNI) 分组比较分析结果显示两组间无显著差异。