RAS Gene Mutation In Colorectal Cancer Patients:Clinical Implication And Relationship With RAL Gtpases Expression

Objective: Colorectal cancer is the most common digestive tract tumor in China and one of the leading causes of cancer deaths worldwide.The etiology of colorectal cancer is complex and involves the interaction of environmental and genetic factors.RAS mutations are common in colorectal cancer.And RAS mutations lead to poor tolerability of tumor treatment and poor prognosis of patients.As a downstream signaling pathway of RAS,RAL protein is considered to be closely related to oncogenic RAS signaling.In our study,we mainly explored the relationship between the RAS gene mutation in colorectal cancer and the clinicopathological features of patients,and its relationship with the expression of RAL protein(RalA and RalB).Methods: One hundred and one colorectal cancer patients were collected from January 2014 to December 2018 in Shengjing Hospital affiliated to China Medical University.RAS gene mutation was detected by Fluorometric PCR.Expression of RalA and Ral B protein was detected by immunhistochemical method.Relationship between RAS mutations and clinicopathological feathures,and its relationship with the expression of RAL GTPases were analyzed by statistical method.Results: Fourty-one cases in 101 cases(40.6)had RAS mutations,KRAS mutations accounted for 40(97%),NRAS mutations accounted for only one(3%),and KRAS exon 2(codon12/13)accounted for 95% of all KRAS mutations and is the most common type of mutation.In the analysis between RAS gene mutation and clinical factors,the RAS mutation rate was lower in patients with lower age(?50)(P=0.011),and three-year survival rate of patients with RAS mutation was significantly lower than that of wild-type patients(p=0.023).The expression of RalA protein was not different between normal tissues and cancer tissues,but the expression of RalB protein was different between normal tissues and cancer tissues(P<0.001).It is highly expressed in cancer tissues and relatively low expressed in adjacent tissues.And the high expression of RalB protein was more closely accociated with RAS-mutant colorectal cancer patients(P=0.045),the high expression of RalB protein was associated with a lower degree of differentiation(P=0.020)and a higher lymph node metastasis rate(P=0.049)in colorectal cancer patients.Conclusions: In our study,KRAS exon 2(codon12/13)was the most common mutations in colorectal cancer.Patients with RAS-mutant colorectal cancer have a lower onset age,a worse prognosis,and a higher RalB protein expression.Patients with high RalB protein expression have lower tissue differentiation and higher lymph node metastasis rate.