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. 2021 Sep;36(9):2501-2512.
doi: 10.1111/jgh.15439. Epub 2021 Feb 18.

A qualitative transcriptional signature of recurrence risk for stages II-III gastric cancer patients after surgical resection

Huarong Zhang  1 , Xiangyu Li  1   2 , Junling Wu  1 , Jiahui Zhang  1 , Haiyan Huang  1 , Yawei Li  1 , Meifeng Li  1 , Shanshan Wang  1 , Jie Xia  1 , Lishuang Qi  3 , Ting Chen  1 , Lu Ao  1   2
Affiliations

A qualitative transcriptional signature of recurrence risk for stages II-III gastric cancer patients after surgical resection

Huarong Zhang et al. J Gastroenterol Hepatol. 2021 Sep.

Abstract

Background and aim: Metastasis is the leading cause of recurrence in gastric cancer. However, the imaging techniques and pathological examinations for tumor metastasis have a high false-positive rate or a high false-negative rate, and many proposed that metastasis-related molecular biomarkers can hardly be validated in independent datasets.

Methods: We propose to use significantly stable gene pairs with reversal relative expression orderings (REOs) between non-metastasis and metastasis gastric cancer samples as the metastasis-related gene pairs. Based on the REOs of these gene pairs, we developed a qualitative transcriptional signature for predicting the recurrence risk of stages II-III gastric cancer patients after surgical resection.

Results: A REOs-based signature, consisting of 19 gene pairs (19-GPS), was selected from 77 stages II-III gastric cancer patients and validated in two independent datasets. Samples in the high-risk group had shorter disease-free survival time and overall survival time than those in the low-risk group. Differentially expressed genes (DEGs) between the high- and low-risk groups classified by 19-GPS were highly reproducible comparing with those between lymph node metastasis and lymph node non-metastasis groups. Functional enrichment analysis showed that these DEGs were significantly enriched in metastasis-related pathways, such as PI3K-Akt and Rap1 signaling pathways. The multi-omics analyses suggested that the epigenetic and genomic features might cause transcriptional differences between two subgroups, which help to characterize the mechanism of gastric cancer metastasis.

Conclusions: The signature could robustly identify patients at high recurrence risk after resection surgery, and the multi-omics analyses might aid in revealing the metastasis-related characteristics of gastric cancer.

Keywords: gastric cancer; multi-omics analysis; recurrence risk; relative expression orderings; transcriptional signature.

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