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

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

4 Scopus Citations
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Author(s)

  • Fuminori Sonohara
  • Naoki Iwata
  • Mitsuro Kanda
  • Masahiko Koike
  • Naoki Takahashi
  • Yasuhide Yamada
  • Yasuhiro Kodera
  • Ajay Goel

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)879-886
Journal / PublicationAnnals of Surgery
Volume269
Issue number5
Online published12 Dec 2017
Publication statusPublished - May 2019

Abstract

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.

Citation Format(s)

Genome-wide Discovery of a Novel Gene-expression Signature for the Identification of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma. / Sonohara, Fuminori; Gao, Feng; Iwata, Naoki; Kanda, Mitsuro; Koike, Masahiko; Takahashi, Naoki; Yamada, Yasuhide; Kodera, Yasuhiro; Wang, Xin; Goel, Ajay.

In: Annals of Surgery, Vol. 269, No. 5, 05.2019, p. 879-886.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal