Work

A Genomewide Transcriptomic Approach Identifies a Novel Gene Expression Signature for the Detection of Lymph Node Metastasis in Patients with Early Stage Gastric Cancer

Year: 2018

Type: article

Abstract: BACKGROUND & AIMS: Although identification of lymph node (LN) metastasis is a well-recognized strategy for improving outcomes in patients with gastric cancer (GC), currently there is lack of availability of adequate molecular biomarkers that can identify such metastasis. Herein we have developed a robust gene-expression signature for detecting LN metastasis in early stage GC by using a transcriptomic-wide biomarker discovery and subsequent validation in multiple clinical cohorts. METHODS: A total of 532 patients with pathological T1 and T2 GC from 4 different cohorts were analyzed. Two independent datasets (n=96, and n=188) were used to establish a gene signature for the identification of LN metastasis in GC patients. The diagnostic performance of our gene-expression signature was subsequently assessed in two independent clinical cohorts using qRT-PCR assays (n = 101, and n = 147), and subsequently compared against conventional tumor markers and image-based diagnostics. RESULTS: We established a 15-gene signature by analyzing multiple high throughput datasets, which robustly distinguished LN status in both testing (AUC = 0.765, 95% CI 0.667 - 0.863) and validation cohorts (AUC = 0.742, 95% CI 0.630 - 0.852). Notably, the 15-gene signature was significantly superior compared to the conventional tumor markers, CEA (P = 0.04) and CA19-9 (P = 0.005), as well as computed tomography-based imaging (P = 0.04). CONCLUSIONS: We have established and validated a 15-gene signature for detecting LN metastasis in GC patients, which offers a robust diagnostic tool for potentially improving treatment outcomes in gastric cancer patients. FUNDING STATEMENT: The present work was supported by the grants CA72851, CA181572, CA184792, CA202797 and CA187956 from the National Cancer Institute; a grant (RP140784) from the Cancer Prevention Research Institute of Texas (CPRIT), pilot grants from the Baylor Sammons Cancer Center, as well as funds from the Baylor Scott & White Research Institute awarded to Ajay Goel, and a VPRT grant (9610337) from the City University of Hong Kong, grants from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. CityU 21101115, 11102317, 11103718), a grant from The Science Technology and Innovation Committee of Shenzhen Municipality (JCYJ20170307091256048) awarded to Xin Wang, and was partially supported by the Shenzhen Research Institute, City University of Hong Kong. DECLARATION OF INTERESTS: None of the authors has any potential conflicts to disclose. ETHICS APPROVAL STATEMENT: Written informed consent was obtained from all patients, and the study was approved by the institutional review boards of all the participating institutions.

Source: EBioMedicine

DOI: 10.1016/j.ebiom.2019.01.057