A genomewide transcriptomic approach identifies a novel gene expression signature for the detection of lymph node metastasis in patients with early stage gastric cancerResearch in context
Daisuke Izumi,
Feng Gao,
Shusuke Toden,
Fuminori Sonohara,
Mitsuro Kanda,
Takatsugu Ishimoto,
Yasuhiro Kodera,
Xin Wang,
Hideo Baba,
Ajay Goel
Affiliations
Daisuke Izumi
Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA; Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; Department of Surgery, Kumamoto General Hospital, Kumamoto, Japan
Feng Gao
Department of Biomedical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong, China
Shusuke Toden
Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA
Fuminori Sonohara
Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA; Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
Mitsuro Kanda
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
Takatsugu Ishimoto
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan; The International Research Center for Medicine Sciences, Kumamoto University, Kumamoto, Japan
Yasuhiro Kodera
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
Xin Wang
Department of Biomedical Sciences, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Hong Kong, China; Shenzhen Research Institute, City University of Hong Kong, Shenzhen, China; Correspondence to: Xin Wang, Department of Biomedical Sciences, City University of Hong Kong, 1B-102, 1/F, Block 1, 31 To Yuen Street, Kowloon Tong, Hong Kong.
Hideo Baba
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
Ajay Goel
Center for Gastrointestinal Research, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA; Correspondence to: Ajay Goel, Center for Gastrointestinal Cancer Research, Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, 3410 Worth Street, Suite 610, Dallas, TX 75246, USA.
Background: 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 transcriptome-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. Findings: We established a 15-gene signature by analyzing multiple high throughput datasets, which robustly distinguished LN status in both training (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 = .04) and CA19–9 (P = .005), as well as computed tomography-based imaging (P = .04). Interpretation: 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. Fund: NIH: CA72851, CA181572, CA14792, CA202797, CA187956; CPRIT: RP140784: Baylor Sammons Cancer Center polot grants (AG), VPRT: 9610337, CityU 21101115, 11102317, 11103718; JCYJ20170307091256048 (XW). Keywords: Gastric cancer, Gene signature, Lymph node metastasis, Prediction, Early stage
