Dataset Information

Prognostic and tumor immunity implication of inflammatory bowel disease-associated genes in colorectal cancer.

ABSTRACT:

Background

Epidemiologic studies continue to emphasize that increasing patients with inflammatory bowel disease (IBD) develop to colorectal cancer (CRC). Although the function and mechanisms of IBD-associated genes (IBDGs) in CRC tumorigenesis have been extensively researched, the implications of IBDGs in the prognosis value and tumor immunity of CRC remain unclear.

Results

In this study, the expression, pathological stages and prognostic value of IBDGs in CRC were systematically analyzed, and 7 prognostic genes including CDH1, CCL11, HLA-DRA, NOS2, NAT2, TIMP1 and TP53 were screened through LASSO-Cox regression analysis. Then, a prognostic signature was established based on the 7 prognostic genes, and the model exhibited a good ability in risk stratification of CRC patients. Subsequent results showed that the genetic alterations of the 7 prognostic genes exhibited more significant and extensive influence on immune cells infiltration in colon adenocarcinoma than that in rectal adenocarcinoma. Meanwhile, immune cells infiltration also showed a significant difference between low-risk group and high-risk group. What's more, 7 prognostic genes-based risk stratification was associated with microsatellite instability, and its prognostic characteristics were significantly negatively correlated with mismatch repair genes.

Conclusions

This study provided a promising insight that the 7 IBDGs could be used as valuable biomarkers for prognostic diagnosis and personalized immunotherapy of CRC patients.

SUBMITTER: Wang D

PROVIDER: S-EPMC9190109 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Prognostic and tumor immunity implication of inflammatory bowel disease-associated genes in colorectal cancer.

Wang Di D Xie Biao B

European journal of medical research 20220613 1

<h4>Background</h4>Epidemiologic studies continue to emphasize that increasing patients with inflammatory bowel disease (IBD) develop to colorectal cancer (CRC). Although the function and mechanisms of IBD-associated genes (IBDGs) in CRC tumorigenesis have been extensively researched, the implications of IBDGs in the prognosis value and tumor immunity of CRC remain unclear.<h4>Results</h4>In this study, the expression, pathological stages and prognostic value of IBDGs in CRC were systematically ...[more]

PMID: 35698180

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Project description:AimTo study the association between inflammatory bowel disease (IBD) and genetic variations in eosinophil protein X (EPX) and eosinophil cationic protein (ECP).MethodsDNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn's disease (CD), 592 with ulcerative colitis (UC) and 300 healthy subjects. The EPX405 (G > C, rs2013109), ECP434 (G > C, rs2073342) and ECP562 (G > C, rs2233860) gene polymorphisms were analysed, by the 5'-nuclease allelic discrimination assay. For determination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylammonium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent assay. The intracellular content of ECP was analysed with the UniCAP(®) system as described by the manufacturer. Statistical tests for calculations of results were χ(2) test, Fisher's exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P < 0.05 were considered statistically significant.ResultsThe genotype frequency for males with UC and with an age of disease onset of ≥ 45 years (n = 57) was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject's genotype frequencies of ECP434 (GG = 57%, GC = 38%, CC = 5%; P = 0.010) and ECP562 (GG = 68%, GC = 29%,CC = 3%; P = 0.009). The genotype frequencies for females, with an age of disease onset of ≥ 45 years with CD (n = 62), was for the ECP434 and ECP562 genotypes GG = 37%, GC = 52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 (P = 0.010) and ECP562 (P = 0.013). The intracellular protein concentration of EPX and ECP was calculated in μg/10(6) eosinophils and then correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 (GG = 4.65, GC = 5.93, and CC = 6.57) and for ECP in the patients with the GG genotype of EPX405 (GG = 2.70, GC = 2.47 and CC = 1.90). ANOVA test demonstrated a difference in intracellular protein content for EPX (P = 0.009) and ECP (P = 0.022). The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference between haplotype distributions for the females with CD (P = 0.003). The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype (34 years) and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype (21 years). For males with UC there was also a difference between the highest and lowest age of the disease onset (EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009). The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dysplasia/cancer was 2.5 (95%CI: 1.2-5.4, P = 0.01) and 2.5 (95%CI: 1.1-5.4, P = 0.02) respectively, compared to patients carrying the GG-genotypes.ConclusionPolymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner, suggesting an essential role of eosinophils in the pathophysiology of IBD.

Project description:Background & aimsA long duration of inflammatory bowel disease (IBD) increases the risk for colorectal cancer. Mutation analysis of limited numbers of genes has indicated that colorectal tumors that develop in patients with IBD differ from those of patients without IBD. We performed whole-exome sequencing analyses to characterize the genetic landscape of these tumors.MethodsWe collected colorectal tumor and non-neoplastic tissues from 31 patients with IBD and colorectal cancer (15 with ulcerative colitis, 14 with Crohn's disease, and 2 with indeterminate colitis) and performed whole-exome sequencing analyses of the microdissected tumor and matched nontumor tissues. We identified somatic alterations by comparing matched specimens. The prevalence of mutations in sporadic colorectal tumors was obtained from previously published exome-sequencing studies.ResultsTwo specimens had somatic mutations in the DNA proofreading or mismatch repair genes POLE, MLH1, and MSH6 and the tumor cells had a hypermutable phenotype. The remaining tumors had, on average, 71 alterations per sample. TP53 was the most commonly mutated gene, with prevalence similar to that of sporadic colorectal tumors (63% of cases). However, tumors from the patients with IBD had a different mutation spectrum. APC and KRAS were mutated at significantly lower rates in tumors from patients with IBD than in sporadic colorectal tumors (13% and 20% of cases, respectively). Several genes were mutated more frequently or uniquely in tumors from patients with IBD, including SOX9 and EP300 (which encode proteins in the WNT pathway), NRG1 (which encodes an ERBB ligand), and IL16 (which encodes a cytokine). Our study also revealed recurrent mutations in components of the Rho and Rac GTPase network, indicating a role for noncanonical WNT signaling in development of colorectal tumors in patients with IBD.ConclusionsColorectal tumors that develop in patients with IBD have distinct genetic features from sporadic colorectal tumors. These findings could be used to develop disease-specific markers for diagnosis and treatment of patients with IBD and colorectal cancer.

Dataset Information

Prognostic and tumor immunity implication of inflammatory bowel disease-associated genes in colorectal cancer.

Background

Results

Conclusions

Publications

Prognostic and tumor immunity implication of inflammatory bowel disease-associated genes in colorectal cancer.

Similar Datasets

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