Gastric Cancer Heterogeneity and Clinical Outcomes

Abstract

Gastric adenocarcinoma is a highly aggressive disease with poor overall survival. The aggressive nature of this disease is in part due to the high intra and inter tumoral heterogeneity and also due to the late diagnosis at presentation. Once progression occurs, treatment is more difficult due to the adaptation of tumors, which acquires resistance to commonly used chemotherapeutics. In this report, using publicly available data sets and pathway analysis, we highlight the vast heterogeneity of gastric cancer by investigating genes found to be significantly perturbed. We found several upregulated genes in the diffuse gastric cancer subtypes share similarity to gastric cancer as a whole which can be explained by the increase in this subtype of gastric cancer throughout the world. We report significant downregulation of genes that are underrepresented within the literature, such as ADH7, GCNT2, and LIF1, while other genes have not been explored within gastric cancer to the best of our knowledge such as METTL7A, MAL, CWD43, and SLC2A12. We identified gender to be another heterogeneous component of this disease and suggested targeted treatment strategies specific to this heterogeneity. In this study, we provide an in-depth exploration of the molecular landscape of gastric cancer in order to shed light onto novel areas of gastric cancer research and explore potential new therapeutic targets.

Keywords: classification; differential gene expression; gastric cancer; microRNA; oncomine.

Figure 1.

Gastric cancer is a highly heterogeneous disease. A, Survival curves taken from the human protein atlas for CWH43, METTL7A, SLC2A12, and MAL. B-D, Protein interaction networks for CWH43, METTL7A, SLC2A12, and MAL taken from the STRING Database. E-H, miRNA interaction networks found from top interactions with CWH43, METTL7A, SLC2A12, and MAL in the miRDb 3.0.

Figure 2.

Male and female patients with gastric cancer have different molecular signatures. A, Density plots of 250 differentially expressed genes in the GSE118916 data set for all gastric cancer cases within the cohort. B, Male and female cohort density plots of the 250 differentially expressed genes in the GSE118916 data set. C-G, STRING Database interaction networks for protein networks from genes found to be differentially expressed in female gastric cancer cases within the cohort (BTD, CAPNS9, EPB41L4B, ADAM17, TOMIL1).

Figure 3.

DMRT1 is found to be differentially expressed in male and female patients with gastric cancer. A, STRING database showing DMRT1 protein interactions. B, Survival curves for DMRT1 taken from the human protein atlas for male and female cohorts. C, Drugs that target DMRT1.