GHRL as a prognostic biomarker correlated with immune infiltrates and progression of precancerous lesions in gastric cancer

Abstract

ObjectiveGhrelin is a protein that regulate appetite and energy balance in the human body, which is encoded by the ghrelin prepropeptide gene (GHRL). GHRL is linked with carcinogenesis and immune regulation. However, the correlation of GHRL to prognosis and tumor-infiltrating lymphocytes in gastric cancer (GC) remains unclear.MethodsIn this study, we assessed the transcriptional expression, prognosis, and different clinicopathological features about GHRL and the correlation between GHRL and tumor infiltration immune cells in GC patients based on the data published in the following databases: TIMER, GEPIA, GEO, STRING, UALCAN, TISIDB, and Kaplan–Meier Plotter. Furthermore, R software analysis for GC Correa’ cascade was also provided. Finally, GHRL expression in GC tissues was assayed using quantitative real-time polymerase chain reaction and immunohistochemistry.ResultsWe found that GHRL expression in GC samples was lower than in normal samples and verified by quantitative PCR (qPCR) and immunohistochemistry. However, sample type, cancer stage, and worse survival were correlated to high GHRL expression. We also found that the expression of GHRL in dysplasia was significantly lower than that in CNAG and in GC. High GHRL expression was connected with immunomodulators, chemokines, and infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in GC.ConclusionsGHRL is a prognostic biomarker for GC patients, and it is correlated with progression of precancerous lesions in GC. It might lead to poor prognosis by regulating tumor immune microenvironment. Studies are important to explore therapeutic targeting GHRL in the future.

Exploring the immune escape mechanisms in gastric cancer patients based on the deep AI algorithms and single‐cell sequencing analysis

“…It may promote tumour progression by enhancing gastric adenocarcinoma cell proliferation, inhibiting apoptosis and promoting angiogenesis. 25 , 26 STC1 (Stanniocalcin 1) is a protein that is highly expressed in gastric adenocarcinoma. It may influence the malignant transformation of tumours by promoting the growth, invasion and metastasis of gastric adenocarcinoma cells.…”

“…GHRL (Ghrelin) is a hormone that is highly expressed in gastric adenocarcinoma and is involved in tumour development by binding to its receptor, GHSR. It may promote tumour progression by enhancing gastric adenocarcinoma cell proliferation, inhibiting apoptosis and promoting angiogenesis 25,26 . STC1 (Stanniocalcin 1) is a protein that is highly expressed in gastric adenocarcinoma.…”

Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies

“…Compared to that in normal tissues, the expression level of ghrelin in the tumor tissues of gastric cancer patients is significantly lower [90,91]. Studies have also observed that the expression of ghrelin in gastric adenocarcinoma cells is almost negligible [92].…”

Tumour‐associated macrophages in gastric cancer: From function and mechanism to application

“…Moreover, overexpressed MAT2A elevated the expression of RIP1 by increasing the H3K4 methylation at its promoter regions to induce the polarisation of M2 TAMs 47 . Several studies have demonstrated that the high expression of TUBA1A, ELK3, GKN2, COL1A2, RAI14, KIF23, GHRL, KCND2, SERPINE1, COL5A2, ALDOC and SLC38A2 and low expression of CD155 and AKR1B10 in GC indicate higher M2 TAM infiltration in the TME using data from public databases 93–107 . Furthermore, TAMs elevated the expression of PI3K‐γ by increasing the uptake of extracellular lipids, thereby inducing M2 phenotype polarisation 44 .…”

“… 47 Several studies have demonstrated that the high expression of TUBA1A, ELK3, GKN2, COL1A2, RAI14, KIF23, GHRL, KCND2, SERPINE1, COL5A2, ALDOC and SLC38A2 and low expression of CD155 and AKR1B10 in GC indicate higher M2 TAM infiltration in the TME using data from public databases. 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 Furthermore, TAMs elevated the expression of PI3K‐γ by increasing the uptake of extracellular lipids, thereby inducing M2 phenotype polarisation. 44 GC cells are characterised by enhanced glycolysis, producing large amounts of lactic acid that can induce the polarisation of M2 TAMs by activating the monocarboxylate channel transporter‐hypoxia inducible factor 1 subunit alpha (MCT–HIF1α) axis in macrophages.…”