Expression And Clinical Significance Of MUC5AC And MUC5B In Colorectal Cancer With Different Microsatellite Status

ObjectiveThis study aims to investigate the relationship between MUC5AC and MUC5B expression levels and microsatellite status in colorectal cancer and their clinicopathological features through both bioinformatics analysis and histological experiments,providing a new theoretical basis for the development and prognostic assessment of colorectal cancer.Methods1.The GEO and TCGA databases were used to screen the differentially expressed genes in colorectal cancer with different microsatellite status and predict the relationship between differentially expressed genes and mismatch repair proteins,and the target genes MUC5AC and MUC5B were selected.2.110 tissue specimens and clinicopathological data of colorectal cancer patients treated by surgery in our hospital from 2016-2021 were collected,and the expression levels of MUC5AC and MUC5B proteins in colorectal cancer tissues were detected by immunohistochemistry,and the relationship between them and the relationship with MMR status and clinicopathological features were analyzed.ResultsⅠ.Bioinformatics screening of microsatellite-related biomarkers for colorectal cancer1.Three datasets,GSE11543,GSE13067 and GSE13294,were selected by GEO database,and there were 9 intersecting genes in MSS/MSI downregulated genes,namely DUSP4,TFF2,CRIP1,SRSF6,CTSE,REG1A,MUC5B,MT1E,MUC5AC;in MSS/MSI up-regulated There were 12 intersecting genes,namely SPINK1,PTPRO,FABP1,CYP2B7P(CYP2B6),TDGF1P3(TDGF1),SLC26A3,MEP1A,CFTR,DPEP1,RBP1,ID1,GABRE.2.Among the down-regulated pooled genes,MUC5B interacts with MUC5AC through gene neighboring,co-expression and protein homology,and it interacts with mismatch repair protein through gene neighboring GALNT12.None of the upregulated pooled genes interacted with mismatch repair proteins3.The expression level of MUC5AC was significantly higher in colorectal cancer tissues compared with paraneoplastic tissues(P>0.05),and high expression of MUC5AC was usually associated with the development of mucinous adenocarcinoma(P<0.05),but not with other clinicopathological features;the expression level of MUC5B was significantly lower in colorectal cancer tissues(P<0.05),and correlated with lymph node metastasis in colorectal cancer patients and histological staging were correlated(P<0.05).Ⅱ.Expression of MUC5AC and MUC5B proteins in colorectal cancer tissues,correlation and relationship with MMR and clinicopathological features1.Expression of MUC5AC in colorectal cancer tissues and its relationship with MMR and clinicopathological features(1)The positive expression rate of MUC5AC in colorectal cancer tissues was significantly higher than that in paracancerous tissues(P=0.000);its expression level was closely correlated with lymph node metastasis(P=0.019)and vascular cancer thrombosis(P=0.010).(2)There was no significant relationship between MUC5AC expression level and MMR status(P=0.523).2.Expression of MUC5B in colorectal cancer tissues and its relationship with MMR and clinicopathological features(1)the positive expression rate of MUC5B in colorectal cancer tissues was significantly lower than that in paracancerous tissues(P=0.004).the expression level of MUC5B was closely related to tumour size(P=0.030)and site of occurrence(P=0.006).(2)The positive rate of MUC5B in colorectal cancer tissues in the dMMR group was significantly higher than that in the pMMR group,and the difference was statistically significant(P=0.011).(3)In colorectal cancer in the dMMR group,MUC5B expression level was closely correlated with tumour size(P=0.030),site of occurrence(P=0.037),and the difference was statistically significant(P<0.05);while in colorectal cancer in the pMMR group,MUC5B expression level was not correlated with clinicopathological features.3.Correlation between MUC5AC and MUC5B protein expression in colorectal cancerA total of 78 cases of 110 colorectal cancer samples were included in the study,and no correlation was found between MUC5AC and MUC5B expression in colorectal cancer(r=-0.075,P=0.513).ConclusionsMUC5AC was highly expressed in colorectal cancer tissues and MUC5B was lowly expressed in colorectal cancer tissues,both of which were correlated with the clinicopathological features of colorectal cancer and both were associated with poor prognosis of colorectal cancer;and the expression level of MUC5B was closely related to the microsatellite status of colorectal cancer.These findings suggest that MUC5AC and MUC5B have an important role in the development of colorectal cancer and are expected to be good biological indicators for assessing the prognosis of colorectal cancer.