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Objective:To analyze the mutation characteristics of Kirsten rat sarcoma virus oncogene homology (KRAS) gene in patients with appendiceal adenocarcinoma and its relationship with the activity of Ras Raf Mitogen activated protein kinase/extracellular regulated protein kinase (MAPK/ERK) signaling pathway.Methods:A total of 41 patients with appendiceal adenocarcinoma who were treated in the Lishui Central Hospital from January 2014 to January 2020 were selected as the observation group, and 50 patients with Appendicitis who were operated at the same time were randomly selected as the control group. Clinical and follow-up data were collected, and the mutation of the KRAS gene in the patient′s tissue was measured using the snapshot method. The expression of key proteins in the MAPK/ERK signaling pathway in cancer tissue was measured using Western blotting (WB) assay. We compared the clinical characteristics and prognosis of patients with KRAS mutation and non KRAS mutation appendiceal adenocarcinoma.Results:The KRAS gene mutation rate in the observation group was higher than that in the control group (41.5% vs 10.0%), and the expression levels of p-ARAF/ARAF, p-MEK1/MEK1, and p-ERK1/ERK1 proteins were also higher than those in the control group. The differences between the groups were statistically significant (all P<0.05). The protein expression levels of p-ARAF/ARAF, p-MEK1/MEK1, p-ERK1/ERK1 in KRAS mutation patients in the observation group were significantly higher than those in non KRAS mutation patients. The proportion of stage IV, positive rates of carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199 and CA125 in KRAS mutation patients were higher than those in non KRAS mutation patients, and the survival time and progression free survival time were shorter than those in non KRAS mutation patients, with statistical significance (all P<0.05). Conclusions:The mutation rate of KRAS in appendix adenocarcinoma is high, and the activation of MAPK/ERK signaling pathway caused by KRAS mutation may play a role in the pathogenesis of appendix adenocarcinoma, which has the value of in-depth research.
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OBJECTIVE: To assess the association between maternal gene polymorphisms of the enzymes involved in folate metabolism and the risk of having a Down syndrome (DS) offspring in southern China mothers. METHODS: Gene polymorphisms in folate metabolizing and the levels of homocysteine (HCY) were analyzed in 84 southern China mothers with DS babies (the case group) and 120 healthy mothers (the control group). Methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) and A1298C (rs1801131), methionine synthase (MTR) A2756G (rs1805087), and methionine synthase reductase (MTRR) A66G (rs1801394) were studied. RESULTS: We found no significant differences (p > .05) in the frequencies of four genetic polymorphisms between the two groups. We found gene-gene interactions had a 1.997-fold increased risk in MTHFR 677 CT with MTR AA (OR: 1.997, 95% CI: 1.038-3.841, p = .038) and a 2.588-fold increased risk in MTHFR 677 CT with MTRR AG (OR: 2.588, 95% CI: 1.111-6.031, p = .028) in the case group than control. The levels of HCY were significantly higher in MTHFR 677 TT than MTHFR 677 CC in the case group (TT 17.2167±5.1051, CC 12.1969±5.0299, F = 2.194, p < .05), and it was significantly higher in MTHFR 677 TT in the case group than control (TT 17.2167±5.1051 in the case group, TT 10.2286±1.4373 in the control group, F = 2.546, p < .05). CONCLUSION: These results suggest that genetic polymorphisms involved in folate metabolism may have population specificity in determining the susceptibility of having DS offsprings. The gene-nutrition, gene-gene interactions and ethnicity are important variables to be considered in periconceptional nutritional supplementation and antenatal care for reducing the risk of DS babies.
