Abstract
Pancreatic adenocarcinomas (PAADs) often remain undiagnosed until later stages, limiting treatment options and leading to poor survival. The lack of robust biomarkers complicates PAAD prognosis, and patient risk stratification remains a major challenge. To address this issue, we established a panel constructed by four miRNAs (miR-4444-2, miR-934, miR-1301 and miR-3655) based on The Cancer Genome Atlas (TCGA) and Human Cancer Metastasis Database (HCMDB) to predicted the prognosis of PAAD patients. Then, a risk prediction model of these four miRNAs was constructed by using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) regression analysis. This model stratified TCGA PAAD cohort into the low-risk and high-risk groups based on the panel-based risk score, which was significantly associated with 1-, 2-, 3-year OS (AUC=0.836, AUC=0.844, AUC=0.952, respectively). The nomogram was then established with a robust performance signature for predicting prognosis compared to clinical characteristics of pancreatic cancer (PC) patients, including age, gender and clinical stage. Moreover, two GSE data were validated the expressions of 4 miRNAs with prognosis/survival outcome in PC. In the external clinical sample validation, the high-risk group with the upregulated expressions of miR-934/miR-4444-2 and downregulated expressions of miR-1301/miR-3655 were indicated a poor prognosis. Furthermore, the cell counting kit-8 (CCK-8) assay, clone formation, transwell and wound healing assay also confirmed the promoting effect of miR-934/miR-4444-2 and the inhibiting effect of miR-1301/miR-3655 in PC cell proliferation and migration. Taken together, we identified a new 4-miRNA risk stratification model could be used in predicting prognosis in PAAD.
Highlights
Pancreatic adenocarcinoma (PAAD) is one of the deadliest tumor types overall
Identification of miR-934 Associated With Metastasis and Poor Prognosis in PAAD
The expression of miR-934 and miR-6510 in Hs766t cells and liver metastasis cell line Hs7667-L3 was verified by qRT-PCR (Figure 1E). miRNA-934 was significantly upregulated in Hs7667-L3 cells
Summary
Pancreatic adenocarcinoma (PAAD) is one of the deadliest tumor types overall. Patients with PAAD who undergo complete tumor resection usually have local or distant recurrence within 2 years [4]. The poor prognosis of PAAD may be due to its invasion, resistance to treatment, and lack of early screening markers and diagnostic methods [5]. Establishing a prognostic assessment model can provide guidance for the personalized treatment for high-risk pancreatic cancer patients to maximize survival time. There is still a need for an assessment system with high sensitivity and specificity to predict the prognosis of PAAD patients. Molecular markers can be used to tailor personalized treatment strategies for patients with inoperable pancreatic cancer, which is important for prognostic assessment [10]
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