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Objective:To investigate the significance of collagen triple helix repeat containing 1 (CTHRC1) gene expression in colon adenocarcinoma based on bioinformatics.Methods:The GEPIA2 analysis tool was used to analyze the expression of CTHRC1 gene in colon adenocarcinoma and the relationship between its expression and the survival prognosis of patients in The Cancer Genome Atlas (TCGA) database and GTEx database. ULACAN analysis tool was used to analyze the methylation level of CTHRC1 gene in colon adenocarcinoma tissues and normal colon tissues in TCGA database. The cBioportal network analysis tool was used to analyze the mutation of CTHRC1 gene. TIMER analysis tool was used to analyze the relationship between CTHRC1 expression and immune cells infiltration, tumor-associated fibroblasts infiltration and functional immune cells. STRING database was used to analyze the proteins interacted with CTHRC1, and the enrichment analyses were performed.Results:The expressions of CTHRC1 gene and protein in colon adenocarcinoma tumor tissues were higher than those in normal colon tissues, and the differences were statistically significant (both P < 0.05), and CTHRC1 gene showed high methylation level in normal colon tissues and low methylation level in tumor tissues ( P < 0.05). A total of 19 mutations were detected in 2 480 colorectal adenocarcinoma and colon adenocarcinoma samples. Among them, 3 cases of colon adenocarcinoma specimens had CTHRC1 mutations, the mutation sites were R235H, A124V and R193C, and the mutation types were all missense mutations. CTHRC1 gene expression was positively correlated with infiltrations of CD8 + T cells, CD4 + T cells, macrophages, neutrophils, dendritic cells and tumor-associated fibroblasts (all P < 0.01). The overall survival and disease-free survival of patients with high expression of CTHRC1 gene were worse than those of patients with low expression of CTHRC1 gene (all P < 0.05). Conclusions:The methylation of CTHRC1 gene and the infiltration of tumor-associated immune cells may have important significances in the pathogenesis of colon adenocarcinoma. CTHRC1 gene expression and immune cells infiltration can be used as predictors of the survival prognosis of colon adenocarcinoma patients.
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Objective To investigate the clinical significances of the expressions of Yes-associated protein 1 (YAP1) and collagen triple helix repeat containing 1 (CTHRC1) in triple-negative breast cancer (TNBC) and their correlations with expression of E-cadherin. Methods Immunohistochemical analysis (SABC) was performed to detect expressions of YAP1 and CTHRC1 in 73 specimens of TNBC and adjacent cancer tissues collected from patients in Dandong First Hospital from January 2006 to December 2017. The correlations between the expressions of YAP1 and CTHRC1 and clinicopathologic features and E-cadherin expression were analyzed. Results The expression rates of YAP1 and CTHRC1 in TNBC were 71.23％(52/73) and 79.45％(58/73), and 13.70％(10/73) and 27.40％(20/73) in adjacent cancer tissues, respectively, and the differences were statistically significant (χ2 values were 49.452 and 39.748, both P< 0.01). The expressions of YAP1 and CTHRC1 were related to tumor grade, clinical stage and lymphatic metastasis (YAP1:χ2 values were 10.244, 8.754, and 6.914, all P<0.05;CTHRC1:χ2 values were 12.582, 13.172, and 6.400, all P< 0.05), but they were not related to patient's age, tumor diameter and menopausal status (all P>0.05). The expressions of YAP1 and CTHRC1 were negatively correlated with expression of E-cadherin in TNBC (r=-0.371, P=0.001;r=-0.323, P=0.005). Conclusion YAP1 and CTHRC1 is closely related to the occurrence and development of TNBC and may participate in the invasion of TNBC through epithelial mesenchymal transition.
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Objective To investigate the proliferation and potential mechanism of CTHRC1 on gastric cancer cells. Methods The cancer tissues and adjacent tissues were collected of 8 gastric cancer patients diagnosed by pathology from Jun. 2017 to Jun. 2018 in Guangzhou Zengcheng People's Hospital. Human gastric mucosal GES-1 cells, and gastric cancer SGC-7901, BGC-823, BGC-803, MKN-45, and MKN-28 cells were purchased from Shanghai Cell Bank of Chinese Academy of Sciences. Western blotting was used to detect the expression of CTHRC1 protein in gastric cancer tissues, paracancerous tissues and gastric cancer cell lines SGC-7901, BGC-823, BGC-803, MKN-45, MKN-28 and human gastric mucosal GES-1 cells. After transfection of gastric cancer SGC-7901 cells with si-CTHRC1 and si-COL1A1, cell proliferation was detected by MTT assay, and the apoptosis rate was detected by flow cytometry. The target gene of CTHRC 1 was predicted by STRING database. Western blotting and immunofluorescence were performed to detect the expression of CTHRC1 and COL1A1 proteins in gastric cancer SGC-7901 cells transfected with si-CTHRC1. The expressions of CTHRC1 and COL1A1 proteins in gastric cancer tissues and the prognosis of gastric cancer patients were analyzed by Kaplan-Meier. Results The expression of CTHRC1 protein was significantly higher in gastric cancer tissues (0.87±0.13) than in adjacent tissues (0.31±0.20, P<0.05). The expression of CTHRC1 protein was higher in gastric cancer cell lines than in human gastric mucosa GES-1 cells with significant difference (P<0.05). The cell proliferation of gastric cancer SGC-7901 cells transfected by si-CTHRC1 decreased significantly. The cell vitality of gastric cancer SGC-7901 cells co-transfected by si-CTHRC1 and si-COL1A1 was lower (0.40±0.07) than those only transfected by si-CTHRC1 (0.87±0.05) or by si-COL1A1 groups (0.83±0.13, P<0.05). The apoptosis rate of gastric cancer SGC-7901 cells transfected by si-CTHRC1 (6.77%±1.55%) was higher than that in NC group (4.80%±1.93%) with statistical significance (P<0.05). The STRING database predicted that COL1A1 was a target gene for CTHRC1. For gastric cancer SGC-7901 cells transfected by si-CTHRC1, the relative expressions of CTHRC1 and COL1A1 proteins were 0.92±0.16 and 1.08±0.23, which were higher than those in NC group (0.55±0.15 and 0.65±0.12) with significant difference (P<0.05). Immunofluorescence showed that the expressions of CTHRC1 and COL1A1 proteins decreased significantly after transfection of si-CTHRC1 into gastric cancer SGC-7901 cells. Kaplan-Meier analysis showed that the 5-year survival rate of patients with high CTHRC1 expression in gastric cancer tissues was significantly lower (27.4%) than that of patients with low CTHRC1 expression (38.4%); The 5-year survival rate of patients with high COL1A1 expression in gastric cancer tissues (20.4%) was significantly lower than that in low expression patients (49.3%), the difference was statistically significant (P<0.001). Conclusion CTHRC1 promotes the proliferation of gastric cancer cells by overexpressing COL1A1 protein.
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Collagen triple helix repeat containing 1 (CTHRC1) can repair the injured vessel by limiting the deposition of collagen and promoting cell migration.CTHRC1 is mainly regulated by Wnt-PCP signaling pathway,transforming growth factor (TGF)-bone morphogenetic protein (BMP) signaling pathway and extracellular signal-regulated kinase (ERK)-matrix metalloproteinase 9 (MMP9) signaling pathway.Recent studies have identified that CTHRC1 is aberrantly expressed in gastrointestinal cancers and associated with the occurring and development of cancers.
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Objective To investigate the expression level of collagen triple helix repeat containing 1 ( CTHRC1) in human gastric carcinoma and the relationship with the clinicopathological characteristics of gastric cancer?Methods The expression of CTHRC1 in human gastric carcinoma and normal gastric mucosa were detected by immunohistochemistry ( S?P method ) , and the correlation with various clinical characteristics, including gender,age,tumor diameter,degree of differentiation,depth of invasion,lymph node metastasis,TNM stage,was analyzed?Results ( 1 ) CTHRC1 expressed positive for 41 cases ( positive rate=53?95%) in 76 gastric carcinoma specimens, but only 1 case ( positive rate=3?33%) expressed positive in 30 normal gastric mucosa,the difference was statistically significant (χ2 =23?0332, P=0?000 )? ( 2 ) In early stage of gastric carcinoma,CTHRC1 was predominantly positive in the nucleus,but with the progression of the tumor,CTHRC1 expressed predominantly in cytoplasm?( 3) The expression of CTHRC1 was correlated with the depth of invasion (P=0?000),lymph node metastasis(P=0?009) and TNM?stage(P=0?007),but not with age,gender,size of the tumor and differentiated degree ( P>0?05 )?Conclusion CTHRC1 might play important roles in the occurrence,invasion and metastasis in human gastric carcinoma,and may be new therapy targets.
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Objective To investigate the effect of influenza virus on the expression of collagen triple he-lix repeat containing 1 (CTHRC1). Methods A549 cells were infected with influenza virus. mRNA and protein levels of CTHRC1 were determined by RT-PCR and Western blot , CTHRC1 levels in the cell supernatants and sera of influenza virus infected patients were determined by enzyme-linked immunosorbent assay (ELISA). The difference of CTHRC1 levels between healthy controls and HCV patients was analyzed. Results Compared with controls, mRNA and protein levels of CTHRC1 were higher in A549 cells infected with H3N2. Serum CTHRC1 levels were higher in influenza virus infected patients than in healthy controls (P < 0.05). Conclusion Influenza virus can promote the synthesis and secretion of CTHRC1.