The Expression And Clinical Significance Of Capn4,P52 And Ki-67 In Colon Cancer

Colon cancer is one of the common malignant gastrointestinal cancers.In recent years,the epidemiological survey result has suggested that colon cancer's incidence and mortality rates in the world are ranked third.The main reason for the progress and death of colon cancer is the infiltration and metastasis of tumor cell.Early diagnosis,early treatment is the important way to improve the survival rates of colon cancer.There are many researches about the occurrence,development,infiltration,metastasis and so on of colon cancer.They are correlated with the mutations,over-expression or decreased expression of genes,but its mechanism is still unclear.Therefore,to further research the molecular mechanism of the the occurrence,development,infiltration,metastasis and so on of colon cancer,may find a new target for the colon cancer screening,treatment and so on.P52 is one of the major components of the non-canonical nuclear factor-?B(NF-?B)signaling pathway.The NF-?B signaling pathway has two activation pathways,the canonical pathway and the non-canonical pathway.Reasearch shows that the over-expression or mutation of NF-?B pathway components can lead to the continuous activation of this pathway.The activation of NF-?B pathway can lead to the expression up of downstream target gene.Some of these target genes are expressed as cytokines that regulate the life activity of cell,such as COX-2,VEGF,Bcl-2,Bax.The abnormal expression of these cytokines can promote the occurrence,infiltration,metastasis and so on of malignant tumors.At present,there are many reasearches about the canonical NF-?B pathway's components,such as P65 and P50 is over-expression in liver cancer,colon cancer,breast cancer and other malignant cancers.However,there are more and more researches on the non-canonical NF-?B pathway's components,such as P52 is over-expressionin esophageal cancer,prostate cancer,cervical cancer and other malignant cancers.Calpain small subunit 1(Capn4)is a small regulatory subunit of the calpains family,which is essential for maintaining the function of the calpains family.The calpains family is an important proteolytic enzyme in airframe,it's involved in a variety of physiological functions,such as cytoskeleton remodeling,signal transduction,cell apoptosis and so on.Its components abnormal expression is involved in the occurrence,development,infiltration,metastasis and so on of many malignant cancers.In recent years,reasearch shows that Capn4 has also been involved in the occurrence,development,infiltration and metastasis of many malignant cancers,such as liver cancer,breast cancer,nasopharyngeal cancer and non-small cell lung cancer and so on.Reasearch shows that Capn4 maybe the downstream target gene of NF-?B pathway,and the activation of NF-?B pathway can promote the expression of Capn4,then promote the occurrence,development,infiltration,metastasis and so on of malignant cancer.At present,research of Capn4 in colon cancer is rare at home.In this reasearch,the expression of Capn4 and P52 in colon cancer and their correlation are studied,to further describe the molecular mechanism of the occurrence,development,infiltration,metastasis and so on of colon cancer,a new target for the colon cancer screening,treatment and so on may be found.The nuclear proliferation index(Ki-67)can reflect the degree of cell division and cell proliferation activity,the higher the expression level,the higher the degree of cell division and the proliferative activity.The expression of Ki-67 is closely related to cell cycle.It can rapidly degrade or lose antigenic determinants after mitosis.It is able to evaluate the cell proliferative activity comprehensively,reliably and objectively.At present,the clinical detection of Ki-67 protein has been used as one of the important indicators for the evaluation of malignant tumor outcome.In this study,the expression of Capn4,P52 and Ki-67 in colon cancer are detected.By analyzing the correlation between Capn4,P52 and Ki-67,and the correlation between them and theclinicopathological features of colon cancer.The molecular mechanism of the occurrence,development,infiltration,metastasis and so on of colon cancer are further described,and a new target for the colon cancer screening,treatment and so on may be found.Objective:In this study,the expression of Capn4,P52 and Ki-67 in colon cancer tissues are detected and they are compared with the normal colon tissues.It investigates the relationship between them and the clinicopathological characteristics of colon cancer and the correlation of these three proteins involving the occurrence,development,infiltration,metastasis and so on of colon cancer.Meanwhile the possibility of Capn4 and P52 become the new molecular markers of colon cancer.Methods:Collected 70 cases of colon cancer tissues and 35 cases of normal colon tissues of pathology wax blocks,all pathology wax blocks are surgically removed,and postoperative pathology confirmed.The expression levels of Capn4,P52 and Ki-67 in these tissues are detected by immunohistochemistry,and to analyze the relationship between Capn4,P52,Ki-67 and clinicopathological characteristics of colon cancer,such as the differentiation status,TNM staging,depth of infiltration and lymph node metastasis and so on.Statistical methods: ?2 test and rank sum test are used to count the data.Spearman correlation analysis is used to analyze the correlation between the data.The difference is statistically significant with P <0.05.Results:Capn4 is mainly expressed in cytoplasm,P52 is expressed in cytoplasm and nucleus,Ki-67 is mainly expressed in nucleus.The positive rates of colon cancer tissues are 74.3%(52/70),70.0%(49/70)and 84.3%(59/70),which are significantly higher than the 22.9%(8/35),31.4%(11/35),17.1%(6/35)of the normal colon tissues(P<0.05).The expression of Capn4,P52 and Ki-67 areclosely related to the TNM staging,depth of infiltration and lymph node metastasis of colon cancer(P <0.05),but there are not correlation between the age,the gender of the patients,and the differentiation grade of colon cancer(P> 0.05).The later the TNM staging,the deeper the infiltration,lymph node metastasis,the higher the expression of Capn4,P52 and Ki-67.And the expression of the two is positively correlated(Capn4 and P52: r=0.869;Capn4and Ki-67: r=0.734;P52 and Ki-67: r=0.638)(P<0.05).Conclusions:In colon cancer,the expression of Capn4,P52 and Ki-67 are significantly higher,suggesting that they may be sensitive indicators of detection of colon cancer.The expression of them is significantly higher in the TNM stage ?~?than ?~?,and the infiltrating serous is significantly higher than that without the infiltration,and the lymph node metastasis is significantly higher than that without lymph node metastasis.It is suggested that Capn4,P52 and Ki-67 may be new indicators of predicting the degree of malignancy and progression of colon cancer.Capn4 is positively correlated with P52.It is suggested that carcinogenic factors may promote the expression of Capn4 through the non-canonical pathway of NF-?B signaling pathway,and then affecting the infiltration,metastasis and so on of colon cancer.It is suggested that Capn4 and P52 may be new targets for the treatment of colon cancer.Both Capn4 and P52 are positively correlated with Ki-67,suggesting that both of them may play a role by participating in regulating the cell cycle of tumor cells.