The Mutations Of ARID1A Gene And The Change And Significance Of ARID1A , PDCD4, PDCD5 And MCL-1 Expression In Colorectal Cancer

Objective:(1) To explore the relationship and significance of ARID1 A, PDCD4, PDCD5 and MCL-1 expression in colorectal cancer tissues.(2) To study the effect of ARID1 A mutations in colorectal cancer tissues. Methods:(1) By immunohistochemical method, we compared the changes of ARID1 A, PDCD4, PDCD5 and MCL-1 expression of 60 cases of colorectal cancer tissues, 20 cases of colorectal adenoma tissues, 20 cases of colorectal inflammation tissues.(2) Direct sequencing test was used to explore the mutations of ARID1 A gene in 40 cases of colorectal cancer. Results:(1) In colorectal cancer tissues, colorectal adenoma tissues and colorectal inflammation tissues, the ARID1 A positive expression rate was respectively 55%(33/60), 80%(16/20), 100%(20/20), there was significant difference among them(P<0.05); the PDCD4 positive expression rate was respectively 41.7%(25/60), 70%(14/20), 100%(20/20), there was significant difference among them(P<0.05); the PDCD5 positive expression rate was respectively 45%(27/60), 75%(15/20), 95%(19/20), there is significant difference among them(P<0.05); the MCL-1 positive expression rate was respectively 76.7%(46/60), 50%(10/20), 40%(8/20), there was significant difference among them(P<0.05).(2) ARID1 A was positively correlated with PDCD4(r=0.357, P=0.008) and PDCD5(r=0.347, P=0.010); MCL-1 was negatively correlated with ARID1A(r =-0.341, P = 0.013), PDCD4(r =-0.333, P = 0.014) and PDCD5(r =-0.372, P = 0.006); PDCD5 was positively correlated with PDCD4(r = 0.391, P = 0.004).(3) The expression of ARID1 A, PDCD4 and MCL-1 in colorectal cancer tissues were associated with TNM staging, lymph node metastasis and 5-year survival(P<0.05); PDCD5 expression in colorectal cancer was not correlated with the patients’ age, gender, lymph node metastasis, TNM staging or 5-year survival(P>0.05).(4) The occurrence of death was closely related with the ARID1 A, PDCD4 and MCL-1 expression, clinical stage, lymph node metastasis(P<0.05). The recurrence was closely related to the expression of ARID1 A and MCL-1(P<0.05), as well as with clinical stage and lymph node metastasis(P<0.05). The cases of ARID1 A, PDCD4, PDCD5 positive expression had better living conditions than the negative cases in colorectal cancer,but the MCL-1 positive expression was the opposite.(5) In 40 colorectal cancer specimens, we found ARID1 A gene was suspected mutation on exon 20-1, which has transition of G to A at codon 249 in three cases. Conclusion:(1) Expression of ARID1 A, PDCD4, PDCD5 and MCL-1have important meanings to prognosis of colorectal cancer. These factors may be involved in the development and metastasis, may have prognostic values or may be used asmolecular targets.(2) Among ARID1 A, PDCD4, PDCD5 and MCL-1 in colorectal cancer have certain relevance, which provide new possibilities for joint prediction and new targeted therapy.(3) A suspected mutation of exon 20-1 of ARID1 A gene was found, and its possible effect on colorectal cancer needs to be determined in the future.