Even though the tumour suppressive role of PTEN is well-known, its prognostic implications are ambiguous. The objective of this study was to further explore the function of PTEN expression in human pancreatic cancer. The expression of PTEN has been dominant in various human cancers including pancreatic cancer when compared with their matched normal tissues. The pancreatic cancer cells have been divided into PTEN blockade-susceptible and PTEN blockade-impassible groups dependent on targeting PTEN by altering intracellular signaling. The expression of PTEN has led to varying clinical outcomes of pancreatic cancer based on GEO Series (GSE) data analysis and Liptak's z analysis. Differential dependency to PTEN blockade has been ascertained based on the expression of polo-like kinase1 PLK1 in pancreatic cancer cells. The prognostic value of PTEN also depends on PLK1 expression in pancreatic cancer. Collectively, the present study provides a rationale for targeting PTEN as a promising therapeutic strategy dependent on PLK1 expressions using a companion biomarker discovery platform.Keywords:PLK1; PTEN; companion biomarker; pancreatic cancer; prognosis.