Expression of KCNN4 in pancreatic cancer tissues, its correlation with prognosis, and impact on pancreatic cancer cell proliferation
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Abstract:
[Abstract] Objective: To investigate the expression of potassium calcium-activated channel subfamily N member 4 (KCNN4) in pancreatic cancer tissues and its impact on tumor progression, and to explore its role in clinical diagnosis and prognosis evaluation of pancreatic cancer. Methods: Using the GEPIA2 data analysis platform, the expression of KCNN4 in pancreatic cancer tissues and its correlation with patient prognosis were analyzed by integrating data from the TCGA and GTEx databases. Cancerous and adjacent non cancerous tissues from 24 patients with pancreatic cancer who underwent surgical resection at ChangHai Hospital of the Naval Medical University were collected. The expression of KCNN4 in pancreatic cancer tissues was validated using qPCR, Western blotting, and immunohistochemical staining. The expression of KCNN4 in human pancreatic cancer cell lines BXPC3 and PANC-1 was knocked down using shRNA. CCK-8 and colony formation assays were performed to detect tumor cell proliferation and growth. A murine KPC cell pancreatic cancer model was established to investigate the effects of KCNN4 knockdown on the growth of orthotopic pancreatic tumor and overall survival (OS) in mice. Results: Analysis of TCGA and GTEx data revealed that KCNN4 was highly expressed in pancreatic cancer tissues (P < 0.05) and was associated with shortened OS and disease-free survival (DFS) in patients (both P < 0.05). The expression levels of KCNN4 mRNA and protein were significantly elevated in pancreatic cancer tissues compared with those in adjacent non-cancerous tissues (all P < 0.01). Knockdown of KCNN4 led to significantly reduced growth rates and fewer colony formations in pancreatic cancer cells (both P < 0.01). The murine orthotopic pancreatic tumor experiment revealed that KCNN4 knockdown inhibited tumor progression and prolonged the OS of mice. Conclusion: KCNN4, highly expressed in pancreatic cancer tissues, promotes pancreatic cancer cell proliferation and tumor progression, and its expression is closely associated with patient prognosis, suggesting that KCNN4 may serve as a promising target for clinical diagnosis and prognosis evaluation of pancreatic cancer.