The Expression And Clinical Significance Of COL10A1 In Pancreatic Cancer

BackgroundPancreatic cancer is one of the most malignant cancer in China and pancreatic ductal adenocarcinoma accounts for 85%of pancreatic cancer.Surgical radical resection is currently the most effective treatment for pancreatic cancer.Over 80%of patients present with unresectable primary tumors and distant metastases at the time of the initial diagnosis.The overall long-term prognosis of pancreatic has not been significantly improved,a 5-year survival rate is no more than 20%in patients who have undergone surgical resection.In recent years,some studies have reported the expression of GRK3,RGS6,IDO and many other functional proteins,which guiding significance in the clinical diagnosis and treatment of pancreatic cancer.Therefore,we need to further explore the pathogenesis of pancreatic cancer and look for more prognostic factors,so as to provide more accurate early diagnosis and prognosis prediction for pancreatic cancer.Collagen X is a member of the collagen superfamily of structural macromolecules,which is encoded by the COL10A1 gene.Collagen X α1 chain(COL10A1)is a specific cleavage fragment of collagen X.It is synthesised specifically and transiently by hypertrophic chondrocytes at sites of endochondral ossification.Collagen X plays an significant role in process of terminal chondrocyte differentiation.Point mutations and deletions in the region of the COL10A1 gene encoding Collagen X have been identified in subjects with metaphyseal chondrodysplasia type Schmid.Overexpression of COL10A1 has been found in diverse solid tumor types such as stomach tumors,testis tumors,ovary tumors,esophagus tumors,breast tumors,colorectal tumors,lung tumors,and bladder tumors.Nonetheless,no literature has reported that the correlation between COL10A1 expression and clinical significance in patients with pancreatic cancer.ObjectiveTo examine the expression of COL10A1 at both the mRNA and protein levels in pancreatic cancer and matching normal pancreatic tissue samples.To explore the correlation between COL10A1 expression and clinicopathologic characteristics and survival time.Methods1.1)Microarray data set(Gene Expression Omnibus(GEO)accession number:GSE15471)from 36 pancreatic ductal adenocarcinoma tumors and paired paracancerous tissues were retrieved from the GEO database.The expression of COL10A1 was visualized by R language to analyze the expression levels of COL10A1 in pancreatic cancer and paired paracancerous tissues.2)Twenty pairs of pancreatic cancer and paired paracancerous tissues were selected.The mRNA expression levels of COL10A1 in pancreatic cancer tissues and paired paracancerous tissues was measured by qPCR;3)Five pairs were randomly selected from 20 pairs of pancreatic cancer tissues and paired paracancerous tissues.The protein expression levels of COL10A1 in pancreatic cancer tissues and paired paracancerous tissues was measured by Western-Blot.2.1)The protein expression levels was analyzed by immunohistochemistry(IHC)in 63 pairs of pancreatic cancer tissues and paired paracancerous tissues,which were in a tissue microarray.The correlation between the expression levels of COL10A1 and the clinical and pathological parameters in patients with pancreatic cancer was analyzed.2)The correlation between COL10A1 expression and prognosis of pancreatic cancer patients was analyzed by Kaplan-Meier and Cox regression.Results1.1)In the GSE15471 microarray data set,the mRNA expression levels of COLA10A1 in pancreatic cancer tissues were substantially higher than the mRNA expression levels of COLA10A1 in paired paracancerous tissues(t=14.216,P<0.001).2)The mRNA expression levels of COLA10A1 in pancreatic cancer tissues were significantly higher than the mRNA expression levels of COLA10A1 in paired paracancerous tissues(t=8.528,p<0.001).3)The protein expression levels of COLA10A1 in pancreatic cancer tissues were significantly higher than the protein expression levels of COLA10A1 in paired paracancerous tissues(t=42.568,p<0.001).2.1)The high expression rate of COL10A1 in cancer tissues was significantly higher than the high expression rate of COL10A1 in paired paracancerous tissues(58.7%vs.23.8%,p<0.01);2)The high expression of COL10A1 protein was strongly related to T stage(χ 2=14.699,p<0.01)and N stage(x2=6.021,p=0.014)of patients with pancreatic cancer;3)High COL10A1 expression was an independent correlation factor for poor postoperative prognosis of patients with pancreatic cancer by Cox regression analysis(HR=2.747,p=0.002);4)Patients with high COL10A1 expression had worse prognosis than those with low COL10A1 expression(χ2=19.820,p<0.001).Conclusion1.The expression levels of COL10A1 in pancreatic cancer tissues is higher than the expression levels of COL10A1 in paired paracancerous tissues;2.The high expression of COL10A1 is related toT stage,and N stage of patients with pancreatic cancer.High COL10A1 expression is an independent correlation factor for poor postoperative prognosis of patients with pancreatic cancer.