| Objective: Colorectal cancer is one of the common gastrointestinal malignancies,its incidence rate is on the rise.Colorectal adenoma is closely related to colorectal cancer,about 80% of colorectal cancer from the evolution of colorectal adenoma,its formation and cancer mechanism is complex and not clear.The role of dyslipidemia in the development of tumors is of increasing concern.Significant increase in lipid metabolism,especially fatty acid synthesis,is an important marker for the rapid proliferation of tumor cells.Unlike the normal cells,in malignant cells the fatty acids that needed to grow and proliferate are mainly derived from the de novo synthesis pathway.SREBP-1 is a key factor in the regulation of fatty acid de novo synthesis pathways(DNL),which directly affects the formation of fatty acid synthetase(FASN),a key enzyme in the synthesis pathway of fatty acids.FASN is the downstream target gene of SREBP-1,both of which are collectively called metabolic proto-oncogenes.Studies had found that fatty acid synthesis pathways have been raised at early stages of different types of tumors and SREBP-1 is highly expressed in tumor cells such as lung cancer,breast cancer and ovarian cancer,but it is rarely reported in colorectal cancer.The activity of SREBP-1 is mainly regulated by PI3K-Akt-mTOR pathway.mTOR up-regulates SREBP-1 expression by increasing TSC1/2 expression and promoting Akt phosphorylation at S473 site.The basic HLH domain of USF1 interacts directly with the HLH domain of the N-terminal region of SREBP-1and also promotes SREBP-1 expression.To explore whether the de novo synthesis pathway of fatty acids play a role in the carcinogenesis of sporadic colorectal adenomas,in this study,the immunohistochemical method was used to detect the expression of SREBP-1,p-mTOR,FASN and USF1 then analyze their relationship with clinical pathological features and the correlation of each other.Further reveal its significance in the carcinogenesis of colorectal adenoma,and provide the theoretical basis for prevention,clinical treatment and prognosis of colorectal cancer.Methods:1 ImmunohistochemistryImmunohistochemical ElivisionTMplus method was used to study the expression of SREBP-1,p-mTOR,FASN and USF1 in 40 cases of normal colorectal mucosa,112 cases of sporadic colorectal tubular adenoma with different dysplasia and 100 cases of colorectal tubular adenoma with carcinomatous changes.And we discussed the correlation between SREBP-1and endogenous fatty acid synthesis-related proteins(mTOR,FASN and USF1),and correlation analysis combined with clinical pathological characteristics.2 Statistical analysisSPSS21.0 software was applicated.The experimental data were analyzed by Chi-square test,wilcoxon test and spearman correlation analysis.P<0.05 was considered statistically significant.Results:1 Immunohistochemical results1.1 The expression of SREBP-1 in the process of colorectal adenoma carcinomatousImmunohistochemical results showed that the positive expression rate gradually increased in the normal colorectal mucosa,tubular adenoma with varying degrees dysplasia and the colorectal carcinoma changed from tubular adenoma(7.5%,37.5%,77.0%,P<0.05).The expression of SREBP-1 in tubular adenoma with varying degrees dysplasia and the colorectal carcinoma is significantly higher than that in the normal colorectal mucosa(P<0.05).The expression of SREBP-1 in colorectal carcinoma is higher than that in the tubular adenoma(P<0.05).The positive expression rate gradually increased intubular adenoma with varying degrees dysplasia(20.0%,35.0%,62.5%,P<0.05).The expression of SREBP-1 in sporadic colorectal tubular adenoma with sever dysplasia is significantly higher than that in the adenoma with moderate/mild dysplasia(P<0.05).But the difference between the expression of SREBP-1in sporadic colorectal tubular adenoma with moderate dysplasia and mild dysplasia has not statistical significance(P>0.05).1.2 The expression of p-mTOR in the process of colorectal adenoma carcinomatousImmunohistochemical results showed that the positive expression rate gradually increased in the normal colorectal mucosa,tubular adenoma with varying degrees dysplasia,and the colorectal carcinoma changed from tubular adenoma(5.0%,34.8%,87.0%,P<0.05).The expression of p-mTOR in tubular adenoma with varying degrees dysplasia and the colorectal carcinoma is significantly higher than that in the normal colorectal mucosa(P<0.05).The expression of p-mTOR in colorectal carcinoma is higher than that in the tubular adenoma(P<0.05).The positive expression rate gradually increased in tubular adenoma with varying degrees dysplasia(17.7%,35.0%,59.4%,P<0.05).The expression of p-mTOR in sporadic colorectal tubular adenoma with sever dysplasia is significantly higher than in the adenoma with mild/moderate dysplasia(P<0.05).The expression of p-mTOR in sporadic colorectal tubular adenoma with moderate dysplasia is significantly higher than in the adenoma with mild dysplasia(P<0.05).1.3 The expression of FASN in the process of colorectal adenoma carcinomatousImmunohistochemical results showed that the abnormal expression rate gradually increased in the normal colorectal mucosa,tubular adenoma with varying degrees dysplasia,and the colorectal carcinoma changed from tubular adenoma(10.0%,32.1%,85.0%,P<0.05).The expression of FASN in tubular adenoma with varying degrees dysplasia and the colorectal carcinoma is significantly higher than that in the normal colorectal mucosa(P<0.05).The expression of FASN in colorectal carcinoma is higher than that in the tubularadenoma(P<0.05).The abnormal expression rate gradually increased in tubular adenoma with varying degrees dysplasia(12.5%,32.5%,56.3%,P<0.05).The expression of FASN in sporadic colorectal tubular adenoma with sever dysplasia is significantly higher than in the adenoma with moderate/mild dysplasia(P<0.05).The expression of FASN in sporadic colorectal tubular adenoma with moderate dysplasia is significantly higher than in the adenoma with mild dysplasia(P<0.05).1.4 The expression of USF1 in the process of colorectal adenoma carcinomatousImmunohistochemical results showed that the positive expression rate gradually increased in the normal colorectal mucosa,tubular adenoma with varying degrees dysplasia,and the colorectal carcinoma changed from tubular adenoma(20.0%,47.3%,65.0%,P<0.05).The expression of USF1 in the colorectal carcinoma is significantly higher than that in the other groups(P<0.05).The expression of FASN in colorectal carcinoma is higher than that in the tubular adenoma(P<0.05).The abnormal expression rate gradually increased in tubular adenoma with varying degrees dysplasia(20.0%,42.5%,87.5%,P<0.05).The expression of FASN in sporadic colorectal tubular adenoma with sever dysplasia is significantly higher than in the adenoma with moderate/mild dysplasia(P<0.05).The expression of FASN in sporadic colorectal tubular adenoma with moderate dysplasia is significantly higher than in the adenoma with mild dysplasia(P<0.05).2 Relationship between the expression of SREBP-1 and endogenous fatty acid synthesis-related proteins(p-mTOR,FASN and USF1)with clinical pathological characteristics2.1 Relationship between the expression of SREBP-1 and clinical pathological characteristicsSREBP-1 protein positive expression rate in tubular adenoma canceration is closely related with tumor differentiation degree.SREBP-1protein positive expression rate increase with the reduction of tumor differentiation degree(?2=18.368,P<0.05)And has nothing to do withpatients' sex,age,adenoma location,lymph-node metastasis,Ducks stages and infiltration depth(P>0.05).2.2 Relationship between the expression of p-mTOR and clinical pathological characteristicsp-mTOR protein positive expression rate in tubular adenoma canceration is closely related with tumor differentiation degree and infiltration depth.p-mTOR protein positive expression rate increase with the reduction of tumor differentiation degree and the increase of and infiltration depth(?2=6.917,?2=7.078,P<0.05).And it is irrelated with patients' age,sex,adenoma location,Ducks stages or lymph node metastasis(P>0.05).2.3 Relationship between the expression of FASN and clinical pathological characteristicsFASN protein positive expression rate in tubular adenoma canceration is closely related with tumor differentiation degree.FASN protein positive expression rate increase with the reduction of tumor differentiation degree(?2=10.080,P<0.05)And has nothing to do with patients' age,sex,adenoma location,lymph-node metastasis,Ducks stages and infiltration depth(P>0.05).2.4 Relationship between the expression of USF1 and clinical pathological characteristicsUSF1 protein positive expression rate in tubular adenoma canceration is closely related with tumor differentiation degree.USF1 protein positive expression rate increase with the reduction of tumor differentiation degree(?2=8.487,P<0.05.And it is irrelated with patients' age,sex,adenoma location,Ducks stages,infiltration depth and lymph node metastasis(P>0.05).3 The relationship between SREBP-1 and endogenous fatty acid synthesis-related proteins(p-mTOR,FASN and USF1)protein expression in the cacinogenesis of sporadic colorectal tubular adenomaResults showed that there is a positive correlation between SREBP-1 and endogenous fatty acid synthesis-related proteins(p-mTOR,FASN and USF1)in the tubular adenoma(r=0.247,r=0.494,r=0.397,P<0.05).Results showthat there is a positive correlation between SREBP-1 and endogenous fatty acid synthesis-related proteins(p-mTOR,FASN and USF1)in the colorectal carcinoma(r=0.231,r=0.702,r=0.247,P<0.05).Conclusion:1 The positive expression rate of SREBP-1 gradually increased with the degree of dysplasia of adenoma and the emergence of cancer,and related with the degree of differentiation of colorectal cancer,which indicate that SREBP-1may participate in the progress of sporadic colorectal adenoma canceration and SREBP-1 protein positive expression rate in tubular adenoma canceration is closely related with tumor differentiation degree.2 The positive expression rate of endogenous fatty acid synthesis-related proteins(p-mTOR,FASN and USF1)gradually increased in the normal colorectal mucosa,tubular adenoma with varying degrees dysplasia and the colorectal carcinoma changed from tubular adenoma.Suggesting that may be related to the occurrence and development of colorectal cancer.3 Results showed that there is a positive correlation between SREBP-1and endogenous fatty acid synthesis-related proteins(p-mTOR,FASN and USF1)which indicates that the combination of SREBP-1 and endogenous fatty acid synthesis-related proteins may play a coordinating role in the carcinogenesis of sporadic colorectal adenoma. |
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