Distinct Expression Patterns of Two Tumor Necrosis Factor Superfamily Member 15 Gene Isoforms in Human Colon Cancer

Abstract

Background Tumor necrosis factor superfamily member 15 ( TNFSF15 ) gene is involved in development of several cancers. It encodes two proteins: tumor necrosis factor ligand-related molecule 1A (TL1A) and vascular endothelial growth inhibitor 192 (VEGI-192). The main receptor for TL1A is death receptor 3 (DR3). Aims We investigated expression of TL1A, VEGI - 192, and DR3 transcripts in different stages of colon cancer and compared them with survival of patients. We also aimed to reveal possible effects of microsatellite instability (MSI) and selected TNFSF15 single-nucleotide polymorphisms (SNPs) on expression of this gene. Methods Forty-five healthy individuals and 95 colon cancer patients were included in the study. Expression of VEGI - 192, TL1A, and DR3 was measured by quantitative PCR. SNP and MSI analyses were performed on DNA isolated from normal or cancer tissue. Results Expression of VEGI - 192 and TL1A was elevated in colon cancer, although the level of VEGI - 192 decreased, while the level of TL1A increased with the progression of cancer. Patients with low expression of TL1A and/or high expression of VEGI - 192 in tumor-transformed tissue showed longer survival. DR3 expression was decreased in the cancer, but it did not change with the tumor progression. Alleles T of rs6478108 and G of rs6478109 SNPs were associated with elevated expression of the TNFSF15 gene. There was no relation between the MSI status and TNFSF15 expression levels. Conclusions Expression of the TNFSF15 gene isoforms was associated with the progression of colon cancer. Levels of TL1A and VEGI - 192 transcripts can be considered as independent prognostic factors for colon cancer.

Prognostic Value of Tumor Mutational Burden Related to Immune Infiltration in Cervical Squamous Cell Carcinoma

“…The TNFSF15 gene is involved in the development of a variety of cancers. For colon cancer, the high expression of TNFSF15 gene isoforms was related to tumor progression and encoded two protein molecules (TL1A and VEGI-192), which can be considered as independent prognostic factors ( 38 ). In addition, some TNFSF15 SNPs have been considered gastric cancer risk factors ( 39 ).…”

Co-Expression and Functional Interactions of Death Receptor 3 and E-Selectin in Clear Cell Renal Cell Carcinoma

“…8,9 TL1A mRNA is abundantly expressed in kidney tissue 7 and colon cancer. 10 Recent studies have reported DR3 expression by some tumors, but its role in tumorigenesis is controversial; it has been implicated as both an anticancer 11 and procancer molecule. 12,13 E-selectin (CD62E, also known as endothelial leukocyte adhesion molecule 1), is a type Ia transmembrane protein that contains lectin-like and epithelial growth factorelike domains, followed by short cysteine-rich repeats.…”

Hypomethylation of TL1A and its decoy receptor 3(DR3) expressive level increase have diagnostic value in HBV-associated cirrhosis

“…[31] The speci c primers of TL1A, TNF-a, IL-6, IL-1β and GAPDH were both described before and the sequences were listed in Table 1. [32][33][34] Enzyme-linked immunosorbent assay (ELISA) Plasma cytokine levels were was measured using the Human Immunoassay Valukine ELISA Kit for TL1A and DR3 (Lengton Bioscience Co, Shanghai, China), which is a competitive method is used to detect the content in samples. According to the manufacturer's protocol, and the absorbance was measured at 450nm.…”