Analysis Of The Effect Of PTK6 Gene Expression On The Prognosis Of Pancreatic Cancer Patients Based On TCGA And GEO Databases

Objective:Pancreatic cancer（PC）is a common gastrointestinal tumor in the world,with high mortality,early metastasis,easy recurrence,and poor prognosis.Most of the patients are highly resistant to chemotherapy and radiotherapy,the effect of radiotherapy is not significant,and the 5-year survival rate is less than 8%,so it is also known as the worst prognosis of gastrointestinal malignancies.Some researchers predict that PC is expected to be the second leading cause of cancer-related deaths in the United States by 2030.Therefore,finding effective prognostic predictors and therapeutic targets is crucial to prolong the survival of PC patients.Protein kinase 6（Protein Tyrosine Kinase6,PTK6）is highly expressed in a variety of cancers,but its expression in PC is unknown.The aim of this study was to investigate the expression of PTK6 in PC and its feasibility as a prognostic predictor and therapeutic target.Methods: The gene expression profiles of GSE28735 and GSE62452 were downloaded from the GEO database,and the expression differences of PTK6 in PC tissues and their paracancerous tissues were analyzed using R software;PC tissues and paracancerous tissues were obtained and grouped using the online GEO2 R tool to obtain co-expression DEGs of GSE28735 and GSE62452,and the obtained DEGs were used for The obtained DEGs were used for enrichment and analysis of the possible molecular mechanisms involved in PTK6.The transcriptome data and clinical information of PC were downloaded from TCGA database,and the gene expression matrix data were obtained by combining the gene expression data and clinical information files.Kaplan-Meier survival analysis was performed using the "survival" package in R software at a statistically significant P<0.05 to analyze the relationship between PTK6 expression levels and clinicopathological characteristics and prognosis of PC patients.We also confirmed the expression of PTK6 in PC by immunohistochemistry.We analyzed the relationship between PTK6 expression and infiltrating immune cells using the databases of TIMER and GEPIA.Results: The expression level of PTK6 gene in PC tissues was significantly higher than that in paraneoplastic tissues in TCGA and GEO databases（P < 0.05）,and the Kaplan-Meier survival curve showed that the overall survival rate（OS）of PTK6 high expression group was significantly lower than that of low expression group（P < 0.01）,meanwhile,the ROC curve showed that PTK6 had a clear diagnostic value for PC（AUC= 0.865,P=0.013,cut-off=2.438）,and univariate and multivariate Cox regression analyses showed that the PTK6 gene expression level and the presence of lymph node metastasis were significantly associated with a poorer prognosis of PC patients（P<0.05）.Immunohistochemical staining results confirmed that PTK6 was highly expressed in PC tissues compared to pancreatic paracancer tissues.Conclusion: PTK6 is highly expressed in PC tissues,and multifactorial Cox regression analysis confirmed that the presence or absence of lymph node metastasis and PTK6 expression level are crucial for the prognosis of PC,therefore,PTK6 may be a valuable prognostic marker and therapeutic target for PC,which provides a new idea for determining the prognosis of PC patients and future precise treatment.