Effect Of Tropomodulin 3 On The Malignant Biological Characteristics Of Pancreatic Carcinoma

Objective Pancreatic carcinoma(PC)is a common and highly aggressive malignancy in clinical practice.Despite the many advances in the diagnosis and treatment of pancreatic cancer,the prognosis of pancreatic cancer remains poor.Therefore,searching for new biomarkers will have a meaningful impact on the early diagnosis and treatment of pancreatic cancer.Tropomodulin 3(TMOD3),a member of the capping protein family,selectively regulates the specialized tropomyosin(TPM)fibrous actin(F-actin)network.It is also regulated by serine/threonine protein kinase 2(AKT2)phosphorylation.These properties allow TMOD3 to possess properties that lead to the acquisition of invasive and metastatic properties by tumor cells,thus playing a vital role in the development of tumor invasion and metastasis.However,there are few reports on TMOD3 on PC.Therefore,the present study was designed to investigate the expression of TMOD3 in pancreatic cancer tissues and the effect of TMOD3 expression level on the clinicopathological characteristics and prognosis of pancreatic cancer.The effects of TMOD3 overexpression and silencing on the biological functions of pancreatic cancer SW1990 cells were investigated separately,and bioinformatics analysis was used to predict the possible signaling pathways regulated by TMOD3 in pancreatic cancer.Methods Firstly,the essential differentially expressed bioinformatics methods screened gene TMOD3,the difference in mRNA expression of TMOD3 in pancreatic cancer and normal pancreatic tissues was analyzed,the impact of the difference in TMOD3 mRNA expression on the clinicopathological characteristics and prognosis of pancreatic cancer patients was investigated.Meanwhile,the gene enrichment analysis was performed.Then,immunohistochemical staining using tissue microarrays was performed to verify and analyze the effect of TMOD3 expression level on the clinicopathological characteristics and prognosis of the obtained pancreatic cancer patients again.Finally,the effects of overexpression and silencing of the TMOD3 gene on the biological functions of pancreatic cancer SW1990 cells,such as proliferation,apoptosis,invasion,and migration,were analyzed by cell experiments.Results Bioinformatics analysis revealed that the expression level of TMOD3 mRNA was significantly higher in pancreatic cancer tissues compared with normal pancreatic tissues(P<0.05),and the expression level of TMOD3 mRNA was associated with the pathological grade(χ2=8.490,P=0.037)and clinical stage of pancreatic cancer patients(χ2=15.548,P=0.001)was strongly correlated.The results of multifactorial COX regression showed that age[HR(95%CI)=1.022(1.001-1.044),P=0.043]and TMOD3 mRNA expression level[HR(95%CI)=2.008(1.311-3.077),P=0.001]were independent risk factors for the prognosis of pancreatic cancer patients,with TMOD3 mRNA high expression group of pancreatic cancer patients had a significantly lower median survival time than the low expression group(Log-rank P<0.001).Upon conducting a pathological characteristic analysis and evaluating tissue microarrays through immunohistochemical staining,it was discovered that pancreatic cancer tissues exhibited a high expression of TMOD3(with P<0.05).This high expression was found to be associated with nerve invasion(χ2=6.146,P=0.013),vascular invasion(χ2=10.101,P=0.001),and clinical stage(χ2=4.121,P=0.040).Furthermore,results from COX regression analysis indicated that clinical stage[HR(95%CI)=2.517(1.446-4.379),P=0.001],vascular invasion[HR(95%CI)=1.763(1.005～3.092),P=0.048],and TMOD3 mRNA expression levels[HR(95%CI)=3.475(1.051～11.490),P=0.041]were identified as independent risk factors for pancreatic cancer patient prognosis.Additionally,TMOD3 gene overexpression was shown to increase pancreatic cancer cell invasion(t=6.040,P=0.004)and migration ability(t=25.426,P<0.001),while silencing TMOD3 resulted in the opposite outcome.These findings provide significant insights into the potential role of TMOD3 in the development and progression of pancreatic cancer.Conclusion Based on the bioinformatics analysis and clinical sample data from tissue microarrays,it has been found that high TMOD3 expression is an independent risk factor for pancreatic cancer prognosis.Additionally,TMOD3 expression correlates with pancreatic cancer patients’malignant pathological features.Cellular assays also suggest that TMOD3 is associated with the migration and invasion of pancreatic cancer cells.Further studies could reveal TMOD3 as a potential new prognostic indicator and therapeutic target for pancreatic cancer.