A robust qualitative transcriptional signature for the correct pathological diagnosis of gastric cancer

Journal of Translational Medicine - Tập 17 - Trang 1-9 - 2019
Haidan Yan1, Meifeng Li1, Longlong Cao2, Haifeng Chen3, Hungming Lai1, Qingzhou Guan1, Huxing Chen1, Wenbin Zhou4, Baotong Zheng1, Zheng Guo1,4, Chaohui Zheng2
1Department of Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
2Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
3Department of General Surgery, Fuzhou Second Hospital Affiliated To Xiamen University, Xiamen, China
4Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China

Tóm tắt

Currently, pathological examination of gastroscopy biopsy specimens is the gold standard for gastric cancer (GC) diagnosis. However, it has a false-negative rate of 10–20% due to inaccurate sampling locations and/or insufficient sampling amount. A signature should be developed to aid the early diagnosis of GC using biopsy specimens even when they are sampled from inaccurate locations. We extracted a robust qualitative transcriptional signature, based on the within-sample relative expression orderings (REOs) of gene pairs, to discriminate both GC tissues and adjacent-normal tissues from non-GC gastritis, intestinal metaplasia and normal gastric tissues. A signature consisting of two gene pairs for GC diagnosis was identified and validated in data of both biopsy specimens and surgical resection specimens pooled from publicly available datasets measured by different laboratories with different platforms. For gastroscopy biopsy specimens, 96.20% of 79 non-GC tissues were correctly identified as non-GC, and 96.84% of 158 GC tissues and six of seven adjacent-normal tissues were correctly identified as GC. For surgical resection specimens, 98.37% of 2560 GC tissues and 97.28% of 221 adjacent-normal tissues were correctly identified as GC. Especially, 97.67% of the 257 GC patients at stage I were exactly diagnosed as GC. We additionally measured 21 GC tissues from seven different GC patients, each with three specimens sampled from three tumor locations with different proportions of the tumor epithelial cell. All these GC tissues were correctly identified as GC, even when the proportion of the tumor epithelial cell was as low as 14%. The qualitative transcriptional signature can distinguish both GC and adjacent-normal tissues from normal, gastritis and intestinal metaplasia tissues of non-GC patients even using inaccurately sampled biopsy specimens, which can be applied robustly at the individual level to aid the early GC diagnosis.

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