Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Jiangsu Simcere Diagnostics Co., Ltd., Nanjing Simcere Medical Laboratory Science Co., Ltd., The State Key Lab of Translational Medicine and Innovative Drug Development, Nanjing, China.
Cancer Med. 2024 May;13(9):e7228. doi: 10.1002/cam4.7228.
The molecular and immunological characteristics of primary tumors and positive lymph nodes in esophageal squamous cell carcinoma (ESCC) are unknown and the relationship with recurrence is unclear, which this study attempted to explore.
A total of 30 ESCC patients with lymph node positive (IIB-IVA) were enrolled. Among them, primary tumor and lymph node specimens were collected from each patient, and subjected to 551-tumor-targeted DNA sequencing and 289-immuno-oncology RNA panel sequencing to identify the different molecular basis and immunological features, respectively.
The primary tumors exhibited a higher mutation burden than lymph nodes (p < 0.001). One-year recurrent ESCC exhibited a higher Mucin16 (MUC16) mutation rate (p = 0.038), as well as univariate and multivariate analysis revealed that MUC16 mutation is independent genetic factor associated with reduced relapse-free survival (univariate, HR: 5.39, 95% CI: 1.67-17.4, p = 0.005; multivariate, HR: 7.36, 95% CI: 1.79-30.23, p = 0.006). Transcriptomic results showed non-relapse group had higher cytolytic activity (CYT) score (p = 0.025), and was enriched in the IFN-α pathway (p = 0.036), while those in the relapsed group were enriched in the TNF-α/NF-κB (p = 0.001) and PI3K/Akt pathway (p = 0.014).
The difference in molecular characteristics between primary lesions and lymph nodes may be the cause of the inconsistent clinical outcomes. Mutations of MUC16 and poor immune infiltration are associated with rapid relapse of nodes-positive ESCC.
食管鳞癌（ESCC）原发肿瘤和阳性淋巴结的分子和免疫特征尚不清楚，与复发的关系也不明确，本研究试图对此进行探索。
共纳入 30 例淋巴结阳性（IIB-IVA）的 ESCC 患者。每位患者均采集原发肿瘤和淋巴结标本，分别进行 551 个肿瘤靶向 DNA 测序和 289 个免疫肿瘤 RNA 测序，以鉴定不同的分子基础和免疫特征。
原发肿瘤的突变负担高于淋巴结（p<0.001）。1 年内复发的 ESCC 具有更高的 Mucin16（MUC16）突变率（p=0.038），单因素和多因素分析显示 MUC16 突变是与无复发生存率降低相关的独立遗传因素（单因素，HR：5.39，95%CI：1.67-17.4，p=0.005；多因素，HR：7.36，95%CI：1.79-30.23，p=0.006）。转录组学结果显示无复发组的细胞毒性（CYT）评分更高（p=0.025），且富含 IFN-α通路（p=0.036），而复发组则富含 TNF-α/NF-κB（p=0.001）和 PI3K/Akt 通路（p=0.014）。
原发灶和淋巴结之间分子特征的差异可能是导致临床结局不一致的原因。MUC16 突变和免疫浸润不良与淋巴结阳性 ESCC 的快速复发相关。
