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

Haidan Yan,Baotong Zheng,Hungming Lai,Qingzhou Guan,Zheng Guo,Chaohui Zheng,Meifeng Li,Haifeng Chen,Huxing Chen,Wenbin Zhou,Longlong Cao

doi:10.1186/s12967-019-1816-4

Abstract

BackgroundCurrently, 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.MethodsWe 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.ResultsA 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%.ConclusionsThe 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.

Highlights

Pathological examination of gastroscopy biopsy specimens is the gold standard for gastric cancer (GC) diagnosis
We found 32,483,417 overlapped gene pairs with the same stable relative expression orderings (REOs) between the gastric normal and gastritis samples, among which six gene pairs had stable but reversal REOs in the GC tissues (Additional files 3 and 4), which were potential GC diagnostic signatures
To further validate the signature, using RNA-seq platform, we measured gene expression profiles of 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

Summary

Introduction

Pathological examination of gastroscopy biopsy specimens is the gold standard for gastric cancer (GC) diagnosis. 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. Only about 10–20% of GC patients are diagnosed at early stage [6, 7]. Most of the false-negative samples (73%) are caused by inaccurate sampling locations and the remainder (27%) could be attributed to pathologist errors [16]

Methods

Results

Discussion

Conclusion