Gender-related differentially expressed genes in pancreatic cancer: possible culprits or accomplices?

Pancreatic cancer (PC) is one of the leading causes of cancer mortality worldwide, and its incidence and mortality rate in several regions is higher in male patients. Although numerous efforts have been made to enhance the clinical outcomes of existing therapeutic regimens, their efficiency is still low, and drug resistance usually occurs in many patients. In addition, the exact underlying molecular basis that makes PC slightly more prevalent among males remains unknown. Providing information regarding the possible association between gender and PC tumorigenesis may offer important clues for how certain molecular cross-talks can affect PC initiation and/or progression. In this study, we used several microarray expression data to identify the common up- and downregulated genes within one specific gender, which were also specified to have binding sites for androgen and/or estrogen receptors. Using functional enrichment analysis among the others, for all the gene sets found in this study, we have shed light on the plausible importance of the androgenic effectors in tumorigenesis, such as the androgen-regulated expression of the GLI transcription factor and the potential role of testosterone in the extracellular matrix (ECM)-cell interaction, which are known for their importance in tumorigenesis. Moreover, we demonstrated that the biological process axon guidance was highlighted regarding the upregulated genes in male patients. Overall, identification of gene candidates as the possible link between gender and PC progression or survival rates may help in developing strategies to reduce the incidence of this cancer.

Automated summary

Pancreatic cancer is a leading cause of cancer mortality worldwide, with higher incidence and mortality rates in male patients. Efforts to improve therapeutic outcomes have been limited by low efficiency and drug resistance. This study identifies genetic factors that may link gender to pancreatic cancer progression and survival rates, highlighting the importance of androgenic effectors and axon guidance in tumorigenesis.