The Role Of Ferroptosis In The Progression Of KRAS Mutant Colorectal Cancer

Research background and purpose:The RAS family is one of the most common mutated genes in human malignancies,including colorectal cancer(CRC).By exploring the relationship between KRAS gene and clinicopathologic features of colorectal cancer patients,as well as the difference in the expression of key genes related to iron death in KRAS mutant and KRAS wild-type CRC tissues,we can understand the prognostic impact of KRAS mutation on colorectal cancer patients,and the role of iron death in KRAS mutant colorectal cancer.In this way,it can provide enlightenment and reference for the treatment strategy of KRAS mutant colorectal cancer.Materials and Methods:1.Detection and analysis of KRAS geneClinicopathologic characteristics of 23 KRAS mutant CRC and 26 KRAS wild CRC were collected: It included the demographic characteristics(age,gender,etc.),blood test indicators(white blood cell count,percentage of neutrophil count),tumor markers(CA199,CEA,etc.),degree of tumor invasion,degree of lymph node metastasis,distant metastasis,tumor stage,tumor size,microsatellite stable state,and immunohistochemistry(vascular invasion,nerve invasion,and swelling)of colorectal cancer patients The degree of tumor differentiation),Chi-square test and T-test were used to compare and analyze the clinicopathologic characteristics of the two groups of patients,and identify the differences between the two groups of patients.Kaplan-Meier method was used to draw the survival curve of the two groups and Log-rank test was used to compare the difference in overall survival between the two groups.COX regression analysis was used to determine the disease risk factors.2.Differential expression of iron death related proteins in KRAS mutant CRCq CR and Western blot were used to compare the expression differences of key genes related to ferroptosis between KRAS mutant and wild-type CRC tissues.Result:The results showed that the KRAS mutant CRC group had deeper tumor invasion depth(p<0.05),larger tumor size(p<0.05),lower tumor differentiation degree(p<0.05),and shorter OS(p<0.05)than the wild-type group.Other indexes,such as the degree of lymphatic metastasis,distant metastasis,blood test indexes,tumor markers,microsatellite stability,did not show significant differences(p > 0.05).Our analysis of the data obtained from the TCGA database also showed that the survival prognosis of patients with KRAS mutant CRC was worse.The expression of key genes related to iron death was different between KRAS mutant and KRAS wild type CRC,and the expression of SLC7A11,Nrf2 and ETS1 proteins was higher in KRAS mutant than in KRAS wild type(P < 0.01).The expressions of Keap1,ATF4 and BAP1 were lower in KRAS mutant than in KRAS wild type(P < 0.01).It is suggested that the activation degree of the classical pathway of ferroptosis in the two groups of tumor tissues is different,which may show different sensitivity to ferroptosis.Conclusion:Compared with KRAS wild-type colorectal cancer,patients with KRAS mutant colorectal cancer showed stronger invasion ability in three key indicators that reflect the invasion and metastasis ability,including the depth of tumor invasion,tumor size and tumor differentiation,suggesting that the existence of KRAS mutation is closely related to the invasion and metastasis of CRC,and the prognosis is worse.The expression of key genes related to ferroptosis was different in KRAS mutant and KRAS wild-type CRC tissues,and the activation degree of ferroptosis classical pathway was different in the two groups of tumor tissues,suggesting that ferroptosis plays an important role in the pathophysiological process of KRAS mutant CRC.