Expression and allele frequencies of Thymic stromal lymphopoietin are a key factor of breast cancer risk

Semlali, Abdelhabib; Almutairi, Mikhlid H.; Parine, Narasimha Reddy; Amri, Abdullah Al; Almeer, Rafa; Alanazi, Mohammad; Rouabhia, Mahmoud

doi:10.1002/mgg3.813

Cited by 7 publications

(9 citation statements)

References 39 publications

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“…Hence, TSLP SNP rs10043985 SNP might be used as biomarker for CRC. However, another SNP of TSLP gene, rs2289276, did not show any significant result with CRC during the comparison with all clinical parameters, indicating that this SNP does not have a role in CRC development as also indicated by other studies [40,43]. In addition, we have identified an association between IL-7R rs1053496 SNP with CRC but only in some of the examined parameters.…”

Section: Discussionsupporting

confidence: 65%

“…In different studies, age plays a role in progression of diseases [ 40 , 41 ]. Therefore, to affirm this study, we have considered age as a parameter.…”

Section: Resultsmentioning

confidence: 99%

“…Following the protocol mentioned in Semlali et al [ 39 , 40 ], the genotype and allele frequencies were computed and checked for deviations with Hardy-Weinberg equilibrium. Case-control and other genetic comparisons were performed using chi-square tests and allelic odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using Fisher’s exact test (two-tailed p values).…”

Section: Methodsmentioning

confidence: 99%

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

Semlali

Almutairi

Alamri

et al. 2021

Genes

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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.

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Section: Discussionsupporting

confidence: 65%

“…In different studies, age plays a role in progression of diseases [ 40 , 41 ]. Therefore, to affirm this study, we have considered age as a parameter.…”

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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

Semlali

Almutairi

Alamri

et al. 2021

Genes

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“…The transcript was detected at high or low expression levels in almost all the patients with the cell surface or intracellular CRLF2 protein. The cases with low expression could be explained by the presence of mutations or singlenucleotide variants modifying the CRLF2 transcript translation rate or half-life [54,55].…”

mentioning

confidence: 99%

CRLF2 and IKZF1 abnormalities in Mexican children with acute lymphoblastic leukemia and recurrent gene fusions: exploring surrogate markers of signaling pathways

Lorenzana

León

et al. 2021

The Journal of Pathology CR

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The gene fusions BCR‐ABL1, TCF3‐PBX1, and ETV6‐RUNX1 are recurrent in B‐cell acute lymphoblastic leukemia (B‐ALL) and are found with low frequency in coexistence with CRLF2 (cytokine receptor‐like factor 2) rearrangements and overexpression. There is limited information regarding the CRLF2 abnormalities and dominant‐negative IKZF1 isoforms associated with surrogate markers of Jak2, ABL, and Ras signaling pathways. To assess this, we evaluated 24 Mexican children with B‐ALL positive for recurrent gene fusions at diagnosis. We found CRLF2 rearrangements and/or overexpression, dominant‐negative IKZF1 isoforms, and surrogate phosphorylated markers of signaling pathways coexisting with recurrent gene fusions. All the BCR‐ABL1 patients expressed CRLF2 and were positive for pCrkl (ABL); most of them were also positive for pStat5 (Jak2/Stat5) and negative for pErk (Ras). TCF3‐PBX1 patients with CRLF2 abnormalities were positive for pStat5, most of them were also positive for pCrkl, and two patients were also positive for pErk. One patient with ETV6‐RUNX1 and intracellular CRLF2 protein expressed pCrkl. In some cases, the activated signaling pathways were reverted in vitro by specific inhibitors. We further analyzed a TCF3‐PBX1 patient at relapse, identifying a clone with the recurrent gene fusion, P2RY8‐CRLF2, rearrangement, and phosphorylation of the three surrogate markers that we studied. These results agree with the previous reports regarding resistance to treatment observed in patients with recurrent gene fusions and coexisting CRLF2 gene abnormalities. A marker phosphorylation signature was identified in BCR‐ABL1 and TCF3‐PBX1 patients. To obtain useful information for the assessment of treatment in B‐ALL patients with recurrent gene fusions, we suggest that they should be evaluated at diagnosis for CRLF2 gene abnormalities and dominant‐negative IKZF1 isoforms, in addition to the analyses of activation and inhibition of signaling pathways.

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“… 39 The expression of TSLP in breast cancer tissue was higher than that in normal tissues and benign tumors. 40 JUN is considered an immune-related biomarker in hepatocellular carcinoma, which influences the active states of B cells and T cells. 41 The NCBI gene database shows that IGKV1-6 and TRAV39 are related to the functions of B cells and T cells, respectively.…”

Section: Discussionmentioning

confidence: 99%

The Combined Detection of Immune Genes for Predicting the Prognosis of Patients With Non-Small Cell Lung Cancer

Tian

Liu

2020

Technol Cancer Res Treat

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Lung cancer is one of the leading causes of cancer-related death. In recent years, there has been an increasing interest in the fields of tumor and immunity. This study focused on the possible prognostic value of immune genes in non-small cell lung cancer patients. We used The Cancer Genome Atlas (TCGA) to download gene expression data and clinical information of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). The immune gene list was downloaded from the Immport database. We then constructed immune gene prognostic models on the basis of Cox regression analysis. We further evaluated the clinical significance of the models via survival analysis, receiver operating characteristic (ROC) curves, and independent prognostic factor analysis. Moreover, we analyzed the associations of prognostic models with both mutation burdens and neoantigens. Using the Gene Expression Omnibus (GEO) and Kaplan–Meier plotter databases, we evaluated the validity of the prognostic models. The prognostic model of LUAD included 13 immune genes, and the prognostic model of LUSC contained 10 immune genes. High-risk patients based on prognostic models had a lower 5-year survival rate than did low-risk patients. The ROC curve analysis demonstrated the prediction accuracy of the prognostic models, as the area under the curve (AUC) was 0.742, 0.707, and 0.711 for LUAD, and 0.668, 0.703, and 0.668 for LUSC, when the predicted survival times were 1, 3, and 5 years, respectively. The mutation burden analysis showed that mutation level was associated with the risk score in patients with LUAD. The analysis based on GEO and Kaplan–Meier plotter demonstrated the prognostic validity of the models. Therefore, immune gene-related models of LUAD and LUSC can predict prognosis. Further study of these genes may enable us to better distinguish between LUAD and LUSC and lead to improvement in immunotherapy for lung cancer.

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Expression and allele frequencies of Thymic stromal lymphopoietin are a key factor of breast cancer risk

Cited by 7 publications

References 39 publications

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

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

CRLF2 and IKZF1 abnormalities in Mexican children with acute lymphoblastic leukemia and recurrent gene fusions: exploring surrogate markers of signaling pathways

The Combined Detection of Immune Genes for Predicting the Prognosis of Patients With Non-Small Cell Lung Cancer

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