基因组分析显示 SCN7A 与食管鳞状细胞癌的预后相关。

Genomic analyses reveal SCN7A is associated with the prognosis of esophageal squamous cell carcinoma.

机构信息

Department of Epidemiology and Health Statistics, The School of Public Health, Fujian Medical University, Fuzhou, Fujian, China.

Key Laboratory of Ministry of Education for Gastrointestinal Cancer, The School of Basic Medical Sciences, Fujian Medical University, 1 Xue Yuan Road, University Town, Fuzhou, 350122, Fujian, China.

出版信息

Esophagus. 2022 Apr;19(2):303-315. doi: 10.1007/s10388-021-00898-y. Epub 2022 Jan 7.

DOI:10.1007/s10388-021-00898-y

PMID:34993672

Abstract

BACKGROUND

Esophageal squamous cell carcinoma (ESCC) has a poor prognosis and occurs with high frequency in China. In particular, Fujian is one of the high-incidence areas of ESCC in China and the somatic mutation profile of ESCC there remains unclear.

PATIENTS AND METHODS

Whole-exome sequencing (WES) was performed in 49 matched ESCC tumor-normal specimens to examine the somatic mutation profiles. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between mutational profile and survival were derived from Cox regression model.

RESULTS

We constructed a preliminary somatic mutation profiling of ESCC in Fujian. Exome sequencing data showed that the main base substitutions in ESCC were C > T transformation (close to 50%), C > A and T > C transversion. The study identified 21 significantly mutated genes, including 8 driver genes and 11 predicted driver genes. Among the 19 driver or predicted driver genes, 9 are novel (OBSCN, PKHD1L1, FSIP2, HRNR, CUBN, CELSR3, SCN7A, TULP4, SRRM2) and 10 have been previously reported. Three mutational signatures were identified to be prevalent in ESCC including Signature_15, Signature_4 and Signature_6, of which Signature_15 was related to prognosis of ESCC (HR 2.81, 95% CI 1.30-6.05; p = 0.008). Survival analysis showed that SCN7A was correlated to overall survival with an HR of 2.76 (95% CI 0.96-7.90, p = 0.058). After controlling for confounding factors such as age, gender, stage and location, the correlation between SCN7A and survival was statistically significant based on multivariate COX regression analysis (HR 4.76, 95% CI 1.20-18.85; p = 0.026, p = 0.053). The tumor vascular invasion was associated with SCN7A of ESCC patients (p = 0.028).

CONCLUSION

In summary, this study provided comprehensive analysis of the somatic mutation profiles of ESCC, and identified SCN7A and Signature_15 for the prognosis of ESCC for the first time. The findings might serve as a conceptual basis for molecular diagnosis and prevention of ESCC.

摘要

背景

食管鳞状细胞癌（ESCC）预后较差，在中国高发。尤其是福建，是中国 ESCC 的高发地区之一，但其 ESCC 的体细胞突变谱尚不清楚。

方法

对 49 对 ESCC 肿瘤-正常标本进行全外显子测序（WES），以检测体细胞突变谱。从 Cox 回归模型中得出突变谱与生存之间关联的风险比（HR）和 95%置信区间（CI）。

结果

我们构建了福建 ESCC 的初步体细胞突变分析。外显子组测序数据显示，ESCC 中的主要碱基替换为 C>T 转换（接近 50%）、C>A 和 T>C 颠换。研究鉴定了 21 个明显突变的基因，包括 8 个驱动基因和 11 个预测的驱动基因。在 19 个驱动或预测的基因中，有 9 个是新的（OBSCN、PKHD1L1、FSIP2、HRNR、CUBN、CELSR3、SCN7A、TULP4、SRRM2），10 个是先前报道的。鉴定出 3 种普遍存在的突变特征，包括 Signature_15、Signature_4 和 Signature_6，其中 Signature_15 与 ESCC 的预后相关（HR 2.81，95%CI 1.30-6.05；p=0.008）。生存分析显示，SCN7A 与总生存相关，HR 为 2.76（95%CI 0.96-7.90，p=0.058）。在控制年龄、性别、分期和部位等混杂因素后，基于多变量 COX 回归分析，SCN7A 与生存之间的相关性具有统计学意义（HR 4.76，95%CI 1.20-18.85；p=0.026，p=0.053）。肿瘤血管侵犯与 ESCC 患者的 SCN7A 相关（p=0.028）。