Expression and Polymorphism of TSLP/TSLP Receptors as Potential Diagnostic Markers of Colorectal Cancer Progression

Abstract

Colorectal cancer (CRC) is the third most common malignancy and the fourth leading cause of cancer-related mortality worldwide. Inflammation is considered as a critical driver for CRC development and growth. We investigated the association between polymorphisms/expression levels of thymic stromal lymphopoietin (TSLP) /TSLP receptors and CRC risk in Saudi population. DNA samples were isolated from blood samples from 220 participants. Case subjects were 112 patients diagnosed with CRC, while control subjects were 108 healthy individuals, who were not diagnosed with any type of malignancy. We selected two single nucleotide polymorphisms (SNPs) located in the thymic stromal lymphopoietin gene (rs10043985 and rs2289276), three SNPs in TSLP receptor gene (TSLPR; rs36139698, rs36177645, and rs36133495), and two other SNPs in interleukin-7 receptor gene (IL-7R; rs12516866 and rs1053496), and designated these SNPs for a case-control genotyping study. The gene expression was analyzed using quantitative RT-PCR and immunohistochemistry assays array on 20 matching colorectal cancer/normal tissues. mRNA expressions and protein levels of TSLP, TSLPR-α subunit, and IL-7R-α subunit showed a 4-fold increase in colon cancer tissues when compared to normal colon tissues. Furthermore, two SNPs (rs10043985 of TSLP and rs1053496 of IL-7R) showed statistically significant correlations with CRC susceptibility. Interestingly, only rs10043985 showed a statistically significant association (p < 0.0001) in the genotypic and phenotypic levels with CRC for all clinical parameters (age, gender, and tumor location) tested. However, IL-7R rs1053496 genotyping results presented a significant correlation (p < 0.05) in male CRC patients and in individuals under 57 years of age. TSLP rs2289276, IL-7R rs12516866, and all TSLPR variants did not display any significant genotypic or phenotypic correlations in all tested clinical parameters. This study identified that TSLP rs10043985 and IL-7R rs1053496 SNPs, and the expression levels of TSLP and TSLPR-α subunit, can be used as markers for CRC development and treatment. However, additional investigations are required on larger group of patients from diverse ethnicities to confirm the genetic association of these variants to CRC.

Role of thymic stromal lymphopoietin in allergy and beyond

“…Increased expression of TSLP and TSLPR has also been reported in colorectal cancer, and the TSLP SNP rs10043985 was shown to be a biomarker for an increased risk of colorectal cancer in the Saudi population 151 . Nevertheless, antitumour effects of TSLP in colorectal cancer have also been reported 152 , with decreased TSLP levels in tumour than in adjacent tissue and TSLP levels negatively correlated with the clinical staging score.…”

MMP2 Polymorphisms and Colorectal Cancer Susceptibility in a Chinese Han Population

“… 15 Semlali et al evaluated the TSLP rs10043985 and IL-7R rs1053496 SNPs and found that they could be used as markers for CRC development in the Saudi population, based on a case–control study. 16 In addition, Li et al found that the ADCY9 polymorphism, rs2230742, was related to an increased risk of CRC in the Chinese Han population. 17 Moreover, the rs12674822 variant of ANGPT2 was reported to be associated with CRC risk in Chinese subjects.…”

A Significant Increasing Risk Association between Cigarette Smoking and XPA and XPC Genes Polymorphisms

“…Each SNP was located either in promoter, intron, or exon regions (Tables S1 and S2), which may lead to a change in the regulation of the protein or modification in protein folding or function. As described by our previous works [23][24][25][26], a total of 8 µL of the final reaction mix and 2 µL of DNA (10 ng/µL) were distributed in an optical reaction plate. The SNP reaction mix contained 5.3 µL of TaqMan ® genotyping master mix (Applied Biosystems, Foster City, CA, USA), 2.5 µL of nuclease-free water, and 0.2 µL of SNP.…”