Abstract
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.
Highlights
Pancreatic cancer is the ninth most common cancer in the United States, with an average of 43,090 deaths from pancreatic cancer reported every 5 years, ranking it as the fourth leading cause of cancer-related death [1]
Initial screening of differential genes in pancreatic cancer and survival analysis The differential expression of genes of laminin family in The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) cohort tumor and non-tumor tissues analyzed by Gene Expression Profiling Interactive Analysis (GEPIA, http://gepia.cancerpku.cn/)
The results show that 9 laminin subunit genes (LAMA2, LAMA3, LAMA4, LAMA5, LAMB1, LAMB2, LAMB3, LAMC1, LAMC2) were highly expressed in tumor tissues of PAAD, with differences that were statistically significant (Figure 1A)
Summary
Pancreatic cancer is the ninth most common cancer in the United States, with an average of 43,090 deaths from pancreatic cancer reported every 5 years, ranking it as the fourth leading cause of cancer-related death [1]. It is the seventh most common cancer diagnosed in men and the fourteenth in women, and the sixth leading cause of cancer deaths in men and eighth in women, with 65,600 new cases of pancreatic cancer (39,200 for men and 26,400 for women) and 63,500 deaths (26,400 for men and 25,800 for women) being reported in 2012 [2]. The most common histological type of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which accounts for most human pancreatic cancer cases (>95%) [4]. As the most commonly used biomarker for the diagnosis of pancreatic cancer, sensitivity and specificity of CA19-9 can be as low as www.aging-us.com
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