Genome-wide Discovery of a Novel Gene-expression Signature for the Identification of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma

被引:11
|
作者
Sonohara, Fuminori [1 ,2 ]
Gao, Feng [3 ]
Iwata, Naoki [1 ]
Kanda, Mitsuro [1 ]
Koike, Masahiko [1 ]
Takahashi, Naoki [4 ]
Yamada, Yasuhide [4 ]
Kodera, Yasuhiro [1 ]
Wang, Xin [3 ]
Goel, Ajay [1 ]
机构
[1] Baylor Univ, Med Ctr, Charles A Sammons Canc Ctr,Baylor Scott & White R, Ctr Gastrointestinal Res,Ctr Translat Genom & Onc, Dallas, TX 75246 USA
[2] Nagoya Univ, Dept Gastroenterol Surg, Grad Sch Med, Nagoya, Aichi, Japan
[3] City Univ Hong Kong, Dept Biomed Sci, Kowloon Tong, 1B-102,1-F,Block 1,31 Yuen St, Hong Kong, Peoples R China
[4] Natl Canc Ctr, Dept Gastrointestinal Med Oncol, Tokyo, Japan
关键词
biomarkers; esophageal squamous cell carcinoma; gene expression; lymph node; NEOADJUVANT CHEMORADIATION; PROGNOSTIC-FACTORS; CANCER; LYMPHADENECTOMY; SURVIVAL; 3-FIELD; NUMBER;
D O I
10.1097/SLA.0000000000002622
中图分类号
R61 [外科手术学];
学科分类号
摘要
Objective: This study aimed to develop a gene-expression signature for identification of lymph node (LN) metastasis in esophageal squamous cell carcinoma (ESCC) patients. Summary of Background Data: LN metastasis is recognized as the most important independent risk factor for therapeutic decision-making of ESCC patients. Methods: A bioinformatic approach was used to analyze RNA sequencing profiles of ESCC patients, and to develop a gene-expression signature for identifying LN metastasis. The robustness of this panel was assessed in 2 independent patient cohorts (n = 56 and 224). Results: We initially prioritized a 16-gene signature out of the total 20,531 mRNAs. The model estimated by these 16 genes discriminated LN status with an area under the curve (AUC) of 0.77 [95% confidence interval (95% CI), 0.68-0.87, 5-fold cross-validation]. Subsequently, a reduced and optimized 5-gene panel was trained in a clinical cohort, which effectively distinguished ESCC patients with LN metastasis (cohort-1: AUC, 0.74: 95% CI, 0.58-0.89; cohort-2, T1 -T2: AUC, 0.74: 95% CI. 0.63-0.86), and was significantly superior to preoperative computed tomography (AUC, 0.61; 95% CI, 0.50-0.72). Furthermore, a combination signature comprising of the 5-gene panel together with the lymphatic vessel invasion (LVI) and venous invasion (VI) demonstrated a significantly improved diagnostic performance compared with individual clinical variables, in both cohorts (cohort-1: AUC, 0.87; 95% CI. 0.78-0.96; cohort-2: AUC, 0.76; 95% CI, 0.65-0.88). Conclusion: Our novel 5-gene panel is a robust diagnostic tool for LN metastasis, especially in early-T stage ESCC patients, with a promising clinical potential.
引用
收藏
页码:879 / 886
页数:8
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