To investigate the expression of fibronectin type Ⅲ domain containing 3B (FNDC3B) in pancreatic cancer and its association with clinicopathological features and prognosis. And to predict the interactions protein network and the possible signal pathways of FNDC3B in pancreatic cancer.

Western blotting was used to analyze the FNDC3B protein expression difference between pancreatic cancer tissues and adjacent normal tissues. Meanwhile, the mRNA expression difference of FNDC3B between pancreatic cancer tissues and pancreatic tissues were analyzed by GEPIA. The pancreatic cancer dataset was collected from the Cancer Genome Atlas (TCGA) database. Statistic software SPSS 25.0 was used to analyze the correlation between expression level of FNDC3B and clinicopathological features and prognosis of pancreatic cancer patients. The survival curve of pancreatic cancer patients was analyzed by Kaplan-Meier method. The STRING database was used to analyze the network of proteins interacting with FNDC3B. Gene set enrichment analysis (GSEA) was used to predict the possible signal pathways of FNDC3B in pancreatic cancer.

Western blotting results showed that FNDC3B protein expression in pancreatic cancer tissues was higher than in adjacent tissues (1.038±0.103 vs. 0.341±0.027, t=22.807, P<0.01). While, GEPIA results showed that FNDC3B mRNA expression in pancreatic cancer tissues was higher than in normal pancreatic tissues (P all<0.05). And FNDC3B mRNA expression level was associated with age (χ²=12.115, P<0.01), pathological grade (χ²=11.490, P<0.01) and N stage (χ²=3.962, P<0.05), not with gender, pathological stage, T stage, M stage (P all<0.05). Univariate Cox analysis results showed that N stage [hazard ratio (HR)=2.001, 95% confidence interval (CI)=1.193-3.354, P<0.01] and FNDC3B mRNA expression level (HR=1.595, 95%CI=1.051-2.421, P<0.05) were correlated with the prognosis of pancreatic cancer patients. Results of multivariate Cox analysis showed that FNDC3B mRNA expression level (HR=1.565, 95%CI=1.011-2.423, P<0.05) was independent factors affecting overall survival of pancreatic cancer patients. Compared with the FNDC3B low expression group, the survival time of pancreatic cancer patients in the FNDC3B high expression group was shorter (χ²=4.898, P<0.05, median survival time: 592 d vs. 634 d). STRING database showed that there was an interaction between FNDC3B and FAM46A (Score=0.687), ZNF46 (Score=0.672), B3GNT7 (Score=0.647), and so on. GSEA research results show that the FNDC3B mRNA high expression samples were enriched into TGF-β signaling pathway, WNT signaling pathway, NOTCH signaling pathway, JAK-STAT signaling pathway, mTOR signaling pathway, and so on (P all<0.05). Moreover, when the expression of FNDC3B gene was up-regulated, the above pathway was activated.

FNDC3B is high expression in pancreatic cancer tissues. And FNDC3B expression level is associated with poor prognosis of pancreatic cancer. Moreover, it promotes progress of pancreatic cancer by regulating interacting proteins such as FAM46A and activating signaling pathways such as TGF-β signaling pathway.

Fibronectin type Ⅲ domain containing 3B; Pancreatic cancer; Expression; Clinical significance