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Study On The Expression And Clinical Significance Of C1GALT1 In Non-small Cell Lung Cancer

Posted on:2021-01-28Degree:MasterType:Thesis
Country:ChinaCandidate:M Z WangFull Text:PDF
GTID:2404330602990840Subject:Oncology
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[Objective]Lung cancer has the highest cancer incidence in terms of both morbidity and mortality,with non-small cell lung cancer being the most common.Traditional surgical methods such as chemotherapy,radiotherapy and other treatments have limited therapeutic effects on lung cancer,and it is difficult to obtain satisfactory therapeutic effects.Glycosylation is an important way of post-translational modification of proteins,and abnormal protein O-glycosylation is considered as a potential marker for malignant tumors.C1GALT1,which is core 1?1,3-galactosyltransferase,is an essential enzyme for the synthesis of core protein 1-incorporated core 1 structure.Studies have found that C1GALT1 is involved in the development of various malignant tumors such as the respiratory tract,injection tract,and urinary tract.It plays an important role and replaces the O-glycosylation modification of various tumor-related proteins,which are mutually involved in the tumor's proliferation,invasion and metastasis,radiotherapy resistance and correction of malignant phenotype metastasis,and also related to the clinicopathological characteristics of patients and the prognosis is closely related.The relationship between expression in non-small cell lung cancer(non-small cell lung cancer,NSCLC)and clinicopathological factors was analyzed,and the relationship between C1GALT1 and post-NSCLC patients was analyzed.[Method]Through the Bioinformation Cancer Gene Atlas(TCGA)database,the C1GALT1 gene expression data of the cancer and adjacent tissues of NSCLC cases and the clinicopathological characteristics and prognostic data of the patients were extracted.Rank sum test and one-way analysis of variance were used to determine the difference in C1GALT1 protein expression between cancer and adjacent cancer cells;immunohistochemical methods were used to detect the expression of cancer and adjacent cancer C1GALT1 protein in pathological tissues of 20 NSCLC patients after surgery to verify the TCGA analysis Chi-square test was used to compare the differences in clinicopathological characteristics.Kaplan-Meier method was used to draw the survival curve,Log-rank test was used to evaluate the survival difference,and single-factor and multi-factor COX proportional hazard models were used to analyze the factors affecting prognosis.[Result]1.In TCGA data,the expression of C1GALT1 gene in 99 patients with cancer and corresponding adjacent tissues was different.The average expression level of C1GALT1 gene in NSCLC tissues of 99 patients was: 2231.51 ± 1171.89,and the average expression level of C1GALT1 gene in corresponding tissues adjacent to cancer was: 1804.34 ± 600.70.Organization,the difference is statistically significant,P value <0.05.2.Immunohistochemical results of C1GALT1 protein in 20 patients with NSCLC and adjacent cancer.In 20 NSCLC patients,the positive expression rate of C1GALT1 protein in cancer tissue was 70%(14/20),and the positive expression rate in adjacent tissues was 0%(0/20).The expression of C1GALT1 protein in cancer tissues was significantly higher than that in normal lungs adjacent to cancer.Organization,the difference is statistically significant,P value <0.05.3.Correlation between C1GALT1 expression and clinicopathological factors.The TCGA data obtained a total of 996 NSCLC patients.The results showed that the expression of C1GALT1 gene was significantly correlated with the patient's gender,smoking status,pathological classification and tumor site,with statistical differences,P <0.05.There was no significant correlation between age,T stage,lymph node metastasis,distant metastasis,past tumor history and C1GALT1 gene expression,P value> 0.05.4.Relationship between C1GALT1 gene expression and prognosis in patients with NSCLC.4.1 Relationship between C1GALT1 gene expression and progression-free survival(PFS)in patients with NSCLCC1GALT1 gene expression is closely related to the prognosis of NSCLC patients and is an independent risk factor that affects the prognosis of PFS in NSCLC patients.The PFS of patients with low expression of C1GALT1 gene was significantly longer than that of patients with high expression,P value <0.05.Kaplan-Meier and Log-rank test evaluation analysis showed that the pathological factors affecting PFS in NSCLC patients were: C1GALT1 gene expression,T stage,lymph node metastasis,pathological type,resection margin,radiotherapy and chemotherapy,all of which had statistical significance,P < 0.05.The age,gender,distant metastasis,previous tumor history,smoking status and site grouping of NSCLC patients are not factors that affect the prognosis of PFS in NSCLC patients,P>0.05.Multi-factor COX proportional hazard model analysis results showed that: C1GALT1 gene expression,T stage,lymph node metastasis,pathological type,previous tumor history,resection margin,and radiotherapy pathological factors are independent influencing factors that affect the prognosis of PFS in NSCLC patients.Statistical significance.However,the chemotherapy factor is not an independent risk factor affecting PFS in NSCLC patients,P> 0.05,no statistical significance.Among them,the risk of recurrence in patients with high expression of C1GALT1 was 1.306 times that of patients with low expression(95% CI: 1.028-1.653,P <0.05).The recurrence risk of T3-4 patients was 1.895 times that of T1-2 patients(95% CI: 1.415 ? 2.539,P <0.05).The risk of recurrence in patients with positive lymph node metastasis(N1)was 1.569 times that of patients with negative lymph node metastasis(N0)(95% CI: 1.213 ? 2.03,P <0.05).The recurrence risk of squamous cell carcinoma is 0.682 times that of adenocarcinoma(95% CI: 0.533 ? 0.873,P <0.05).The recurrence risk of patients with a previous history of cancer was 1.480 times that of patients without a history of cancer(95% CI: 1.092 ? 2.008,P <0.05).The recurrence risk of patients with R1-2 margin was 2.092 times that of patients with R0 margin(95% CI: 1.134 ? 3.859,P <0.05).The risk of recurrence of patients with radiotherapy was 1.555 times that of patients without radiotherapy(95% CI: 1.134 ? 2.13,P <0.05).The risk of recurrence in patients with chemotherapy was 0.866 times that of patients without chemotherapy(95% CI: 0.653 ? 1.147,P> 0.05).4.2 Relationship between C1GALT1 gene expression and overall survival(OS)in patients with NSCLCThe C1GALT1 gene is closely related to the OS of NSCLC patients and is an independent risk factor that affects the prognosis of OS in NSCLC patients.The OS of patients with low expression of C1GALT1 gene was better than that of patients with high expression of C1GALT1 gene,P value <0.05.Kaplan-Meier and Log-rank test evaluation analysis showed that the pathological factors affecting the OS of NSCLC patients were: C1GALT1 gene,patient's age,T stage,lymph node metastasis,distant metastasis,resection margin,radiotherapy and chemotherapy factors,all with statistics Academic significance,P <0.05.The gender,pathological type,previous tumor history,smoking status and local group pathological factors were not the single risk factors affecting the prognosis of OS,P>0.05.Multi-factor COX proportional hazards model analysis results showed that: C1GALT1 gene expression,T stage,lymph node metastasis,resection margin,radiotherapy,chemotherapy and age pathological factors are independent risk factors that affect the OS of NSCLC patients,P values are all <0.05,with statistical significance.Whether distant metastasis is not an independent risk factor affecting the OS of NSCLC patients,P = 0.087,has no statistical significance.The risk of death of patients with high expression of C1GALT1 was 1.234 times that of patients with low expression(95% CI: 1.01-1.511,P <0.05).The risk of death in T3-4 patients was 1.589 times that of T1-2 patients(95% CI: 1.231 ? 2.051,P <0.05).The mortality risk of N1 patients was 1.691 times that of N0 patients(95% CI: 1.357-2.107,P <0.05).The risk of death in patients with R1-2 margin is 2.175 times that of R0(95% CI: 1.304 ? 3.627,P <0.05).> The risk of death for patients aged 60 years is 1.22 times that of patients aged ?60 years(95% CI: 0.957 ? 1.555,P> 0.05).The mortality risk of patients with radiotherapy was 1.364 times that of patients without radiotherapy(95% CI: 1.006 ? 1.851,P <0.05).The death risk of patients with chemotherapy was 0.673 times that of patients without chemotherapy(95% CI: 0.517 ? 0.877,P <0.05).The risk of death with distant metastasis(M1)was 1.68 times that of patients without distant metastasis(M0)(95% CI: 1.026 ? 2.752,P> 0.05).[Conclusion]1.The expression of C1GALT1 at the level of genes and proteins in cancer tissues of NSCLC patients is significantly higher than that of normal tissues adjacent to the cancer.2.The expression of C1GALT1 gene has significant correlation with the patient's gender,smoking status,pathological classification,and tumor site.3.The expression of C1GALT1 gene is an independent risk factor affecting the prognosis of NSCLC.The prognosis of patients with low expression of C1GALT1 gene is significantly better than that of patients with high expression.4.C1GALT1 gene is involved in the occurrence and development of small cell lung cancer.C1GALT1 may be a new potential target for diagnosis and treatment of NSCLC.
Keywords/Search Tags:C1GALT1, NSCLC, differential expression, poor prognosis
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