Analysis of Gastric Cancer Transcriptome Allows the Identification of Histotype Specific Molecular Signatures With Prognostic Potential

Abstract

Gastric cancer is the fifth most common malignancy but the third leading cause of cancer-associated mortality worldwide. Therapy for gastric cancer remain largely suboptimal making the identification of novel therapeutic targets an urgent medical need. In the present study we have carried out a high-throughput sequencing of transcriptome expression in patients with gastric cancers. Twenty-four patients, among a series of 53, who underwent an attempt of curative surgery for gastric cancers in a single center, were enrolled. Patients were sub-grouped according to their histopathology into diffuse and intestinal types, and the transcriptome of the two subgroups assessed by RNAseq analysis and compared to the normal gastric mucosa. The results of this investigation demonstrated that the two histopathology phenotypes express two different patterns of gene expression. A total of 2,064 transcripts were differentially expressed between neoplastic and non-neoplastic tissues: 772 were specific for the intestinal type and 407 for the diffuse type. Only 885 transcripts were simultaneously differentially expressed by both tumors. The per pathway analysis demonstrated an enrichment of extracellular matrix and immune dysfunction in the intestinal type including CXCR2, CXCR1, FPR2, CARD14, EFNA2, AQ9, TRIP13, KLK11 and GHRL. At the univariate analysis reduced levels AQP9 was found to be a negative predictor of 4 years survival. In the diffuse type low levels CXCR2 and high levels of CARD14 mRNA were negative predictors of 4 years survival. In summary, we have identified a group of genes differentially regulated in the intestinal and diffuse histotypes of gastric cancers with AQP9, CARD14 and CXCR2 impacting on patients’ prognosis, although CXCR2 is the only factor independently impacting overall survival.

Next-Generation Sequencing Analysis of Gastric Cancer Identifies the Leukemia Inhibitory Factor Receptor as a Driving Factor in Gastric Cancer Progression and as a Predictor of Poor Prognosis

“…The GC is a phenotypically and genotypically heterogeneous disease driven by multiple causative factors, including environmental factors and diet, Helicobacter (H.) pylori or Epstein–Barr virus (EBV) infection and host genetics ( 4 , 5 ). According to the classical Lauren’s classification, GC is subdivided into three main histological subtypes: diffuse, intestinal, and mixed ( 6 , 7 ). The diffuse subtype is generally more aggressive and predicts treatment resistance and poor prognosis ( 8 ).…”

Identification of circRNA–miRNA–Immune-Related mRNA Regulatory Network in Gastric Cancer

“…FGF10, a secreted factor, stimulated the proliferation of lung cancer cells ( 28 ). In GC, FGF10 was involved in several signaling pathways ( 29 ). Tgd cells were related to the prognosis of patients with stomach adenocarcinoma ( 30 ).…”

Phenotypic spectrum of FGF10-related disorders: a systematic review

“…Deregulation of FGF10-related signaling pathways was also associated with gastric cancer ( Carino et al, 2021 ). This assumption was further supported by Wu et al, who indicated that regulatory networks involving FGF10 play an essential role in gastric cancer proliferation, migration, and invasion ( Wu, Liu & Zhang, 2022 ).…”