Analyses of the Expression and Prognosis of ILDR1 in Human Gastric Cancer

Overview

Journal Heliyon

Specialty Social Sciences

Date 2022 Sep 12

PMID 36091962

Authors

Li Wang

Rujun Zhai

Guodong Song

Yong Wang

Affiliations

Soon will be listed here.

Abstract

The worldwide mortality rate of gastric cancer worldwide remains high. Immunoglobulin-like domain containing receptor 1 (ILDR1) belongs to an evolutionarily conserved protein family, and little is known about this gene in gastric cancer. In this paper, we analyzed the expression of ILDR1 and its relationship with clinical outcomes in gastric cancer using publicly available databases. ONCOMINE, GEPIA2, UALCAN, Kaplan-Meier Plotter, cBioPortal, GeneMANIA and LinkedOmics databases were used to analyze the expression, prognostic values, mutations and functional networks of ILDR1 in gastric cancer. We observed that ILDR1 was overexpressed in gastric cancer than in normal tissues. ILDR1 expression was significantly higher in patients with gastric cancer than in normal controls during subgroup analysis based on cancer stage, patient's race, sex, age, tumor grade, infection, histological subtype, and nodal metastasis status. Survival analysis showed that upregulation of ILDR1 expression was significantly associated with poor prognosis. Genomic alterations in ILDR1 were analyzed using cBioPortal, protein-protein interaction (PPI) networks were constructed using GeneMANIA and the co-expressed genes, gene ontology, and pathways of ILDR1 were determined using the LinkedOmics web tool. ILDR1 showed significant differences in expression between gastric cancer and normal tissues and, thus, may be a promising prognostic biomarker for gastric cancer.

Citing Articles

Population-enriched innate immune variants may identify candidate gene targets at the intersection of cancer and cardio-metabolic disease.

Yeyeodu S, Hanafi D, Webb K, Laurie N, Kimbro K Front Endocrinol (Lausanne). 2024; 14:1286979.

PMID: 38577257 PMC: 10991756. DOI: 10.3389/fendo.2023.1286979.

An unappreciated cell survival-independent role for BAFF initiating chronic lymphocytic leukemia.

Ullah M, Garcillan B, Whitlock E, Figgett W, Infantino S, Eslami M Front Immunol. 2024; 15:1345515.

PMID: 38469292 PMC: 10927009. DOI: 10.3389/fimmu.2024.1345515.

References

Rhodes D, Kalyana-Sundaram S, Mahavisno V, Varambally R, Yu J, Briggs B . Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia. 2007; 9(2):166-80. PMC: 1813932. DOI: 10.1593/neo.07112. View

Chandra R, Wang Y, Shahid R, Vigna S, Freedman N, Liddle R . Immunoglobulin-like domain containing receptor 1 mediates fat-stimulated cholecystokinin secretion. J Clin Invest. 2013; 123(8):3343-52. PMC: 3726170. DOI: 10.1172/JCI68587. View

Cerami E, Gao J, Dogrusoz U, Gross B, Sumer S, Aksoy B . The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov. 2012; 2(5):401-4. PMC: 3956037. DOI: 10.1158/2159-8290.CD-12-0095. View

Emami N, Cavazos T, Rashkin S, Cario C, Graff R, Tai C . A Large-Scale Association Study Detects Novel Rare Variants, Risk Genes, Functional Elements, and Polygenic Architecture of Prostate Cancer Susceptibility. Cancer Res. 2020; 81(7):1695-1703. PMC: 8137514. DOI: 10.1158/0008-5472.CAN-20-2635. View

Gao J, Aksoy B, Dogrusoz U, Dresdner G, Gross B, Sumer S . Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal. 2013; 6(269):pl1. PMC: 4160307. DOI: 10.1126/scisignal.2004088. View

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. DOI: 10.3322/caac.21492. View

Vasaikar S, Straub P, Wang J, Zhang B . LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res. 2017; 46(D1):D956-D963. PMC: 5753188. DOI: 10.1093/nar/gkx1090. View

Bednarz-Misa I, Fortuna P, Diakowska D, Jamrozik N, Krzystek-Korpacka M . Distinct Local and Systemic Molecular Signatures in the Esophageal and Gastric Cancers: Possible Therapy Targets and Biomarkers for Gastric Cancer. Int J Mol Sci. 2020; 21(12). PMC: 7349922. DOI: 10.3390/ijms21124509. View

Kang M, Choi H, Oshima M, Cheong J, Kim S, Lee J . Estrogen-related receptor gamma functions as a tumor suppressor in gastric cancer. Nat Commun. 2018; 9(1):1920. PMC: 5954140. DOI: 10.1038/s41467-018-04244-2. View

10.

An J, Yang J, Wang Y, Wang Y, Xu B, Xie G . Targeted Next Generation Sequencing Revealed a Novel Homozygous Mutation in Gene Causes Autosomal Recessive Nonsyndromic Sensorineural Hearing Loss in a Chinese Family. Front Genet. 2019; 10:1. PMC: 6370629. DOI: 10.3389/fgene.2019.00001. View

11.

Kim N, Higashi T, Lee K, Kim A, Kitajiri S, Kim M . Downsloping high-frequency hearing loss due to inner ear tricellular tight junction disruption by a novel ILDR1 mutation in the Ig-like domain. PLoS One. 2015; 10(2):e0116931. PMC: 4323246. DOI: 10.1371/journal.pone.0116931. View

12.

Hauge H, Patzke S, Delabie J, Aasheim H . Characterization of a novel immunoglobulin-like domain containing receptor. Biochem Biophys Res Commun. 2004; 323(3):970-8. DOI: 10.1016/j.bbrc.2004.08.188. View

13.

Liu Y, Nie H, Liu C, Zhai X, Sang Q, Wang Y . Angulin proteins ILDR1 and ILDR2 regulate alternative pre-mRNA splicing through binding to splicing factors TRA2A, TRA2B, or SRSF1. Sci Rep. 2017; 7(1):7466. PMC: 5547134. DOI: 10.1038/s41598-017-07530-z. View

14.

Szasz A, Lanczky A, Nagy A, Forster S, Hark K, Green J . Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients. Oncotarget. 2016; 7(31):49322-49333. PMC: 5226511. DOI: 10.18632/oncotarget.10337. View

15.

Kwon M, Kim S, Choi Y, Jung H, Balch C, Kim S . Derepression of CLDN3 and CLDN4 during ovarian tumorigenesis is associated with loss of repressive histone modifications. Carcinogenesis. 2010; 31(6):974-83. PMC: 2878357. DOI: 10.1093/carcin/bgp336. View

16.

Ahmad R, Kumar B, Chen Z, Chen X, Muller D, Lele S . Loss of claudin-3 expression induces IL6/gp130/Stat3 signaling to promote colon cancer malignancy by hyperactivating Wnt/β-catenin signaling. Oncogene. 2017; 36(47):6592-6604. PMC: 6512312. DOI: 10.1038/onc.2017.259. View

17.

Chau I . Checkpoint inhibition: an ATTRACTION in advanced gastric cancer?. Lancet. 2017; 390(10111):2418-2419. DOI: 10.1016/S0140-6736(17)32131-1. View

18.

Higashi T, Katsuno T, Kitajiri S, Furuse M . Deficiency of angulin-2/ILDR1, a tricellular tight junction-associated membrane protein, causes deafness with cochlear hair cell degeneration in mice. PLoS One. 2015; 10(3):e0120674. PMC: 4378975. DOI: 10.1371/journal.pone.0120674. View

19.

Morozko E, Nishio A, Ingham N, Chandra R, Fitzgerald T, Martelletti E . ILDR1 null mice, a model of human deafness DFNB42, show structural aberrations of tricellular tight junctions and degeneration of auditory hair cells. Hum Mol Genet. 2014; 24(3):609-24. PMC: 4291242. DOI: 10.1093/hmg/ddu474. View

20.

Hempstock W, Sugioka S, Ishizuka N, Sugawara T, Furuse M, Hayashi H . Angulin-2/ILDR1, a tricellular tight junction protein, does not affect water transport in the mouse large intestine. Sci Rep. 2020; 10(1):10374. PMC: 7316798. DOI: 10.1038/s41598-020-67319-5. View