A poor outcome for pancreatic ductal adenocarcinoma (PDAC) patients is still a challenge worldwide. The aim of our study is to investigate the potential of key laminin subunits for being used both as a diagnostic and prognostic biomarker for PDAC patients. We evaluated the mRNA expression and prognostic value of laminin gene family in PDAC tissues using online public databases. Moreover, the relationship between key laminin subunits in PDAC blood cells and circulating tumor cells (CTCs) and the distinguishing ability of joint serum levels with carbohydrate antigen 19-9 (CA19-9) was analyzed. Two key differentially expressed subunits (LAMA3 and LAMC2) that are associated with prognosis of PDAC patients were found to show a potential for distinguishing between PDAC and non-tumor tissues. LAMA3 and LAMC2 expression were found to be positively related with CTC quantity in PDAC blood (R=0.628, p=0.029; R=0.776, p=0.003, respectively) using IgG chips. Furthermore, serum LAMC2 levels offered significant improvement over using CA19-9 alone for the discrimination of PDAC. Joint serum LAMC2 and CA19-9 levels increased the net benefit proportion in early stage/operational PDAC patients. Using integrated profiling, we identified LAMA3 and LAMC2 as potential therapeutic targets and prognostic markers for PDAC, for which further validation is warranted.