Aims: Baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) plays vital roles in carcinogenesis by influencing cell division and proliferation and by inhibiting apoptosis. However, the prognostic significance of BIRC5 remains unclear in breast cancer. Methods: BIRC5 expression and methylation status were evaluated using the Oncomine and The Cancer Genome Atlas (TCGA) databases. The relevance between BIRC5 and different clinicopathological features as well as survival information was analyzed using the bc-GenExMiner database and Kaplan-Meier Plotter. BIRC5-drug interaction network was obtained using the Comparative Toxicogenomics Database. Results: Based on the results from databases and own hospital data, BIRC5 was higher expressed in different breast cancer subtypes compared with the matched normal individuals. Hormone receptors were negatively correlated with BIRC5 expression, whereas the Scarff-Bloom-Richardson (SBR) grade, Nottingham Prognostic Index (NPI), human epidermal growth factor receptor-2 (HER-2) status, basal-like status, and triple-negative status were positively related to BIRC5 level in breast cancer samples with respect to normal tissues. High BIRC5 expression was responsible for shorter relapse-free survival, worse overall survival, reduced distant metastasis free survival, and increased risk of metastatic relapse event. BIRC5-drug interaction network indicated that several common drugs could modulate BIRC5 expression. Furthermore, a positive correlation between BIRC5 andcell-division cycle protein 20 (CDC20) gene was confirmed. Conclusion: BIRC5 may be adopted as a promising predictive marker and potential therapeutic target in breast cancer. Further large-scale studies are needed to more precisely confirm the value of BIRC5 in treatment of breast cancer.The Breast Cancer Gene-Expression Miner v4.1 (bc-GenExMiner v4.1, http://bcgenex.centregauducheau.fr/BC-GEM), an open access database of published annotated genomics data, was utilized to analyze the relevance between BIRC5 and specific clinicopathological features of breast cancer [16,17]. Association between BIRC5 and metastatic relapse event was assessed using the prognostic module, and correlation of BIRC5 and co-expressed cell-division cycle protein 20 (CDC20) was evaluated using the correlation module. UCSC XenaThe UCSC Xena browser (http://xena.ucsc.edu/) was used to analyze the TCGA Breast Cancer data using the level 3 data. The heatmap and correlation between BIRC5 and CDC20 were then constructed. Kaplan-Meier PlotterThe Kaplan-Meier Plotter (http://kmplot.com/analysis/), a web tool capable to check the effect of 54675 genes on survival using 5143 clinical breast cancer samples, was applied to show the prognostic value of BIRC5 in relapse-free survival, overall survival, and distant metastasis-free survival [18]. The hazard ratio (HR) with 95% confidence interval (CI), and log-rank P-value were calculated automatically.

Pancreatic cancer (PC) is one of the most deadly digestive cancers world-wide, with a dismal five-year survival rate of <8%. Upregulation of transmembrane protein 158 (TMEM158) is known to facilitate the progression of several carcinomas. However, little is known concerning the potential roles of TMEM158 in PC. Herein, we first found that TMEM158 was significantly upregulated in PC samples as well as PC cell lines. The overexpression of TMEM158 was significantly correlated with advanced clinicopathologic features (including tumor size, TNM stage, and blood vessel invasion) and poorer prognosis of patients with PC in clinic. Evidenced based on a series of loss-and gain-of-function assays uncovered that TMEM158 enhanced PC cell proliferation, migration, and invasion by stimulating the progression of cell cycle, epithelial-mesenchymal transition, and MMP-2/9 production. Furthermore, mechanism-related investigations disclosed that activation of TGFβ1 and PI3K/AKT signal might be responsible for TMEM158-triggered PC aggressiveness. Collectively, TMEM158 was upregulated in PC and promoted PC cell proliferation, migration, and invasion through the activation of TGFβ1 and PI3K/AKT signaling pathways, highlighting its potential as a tumor promoter and a therapeutic target for PC. K E Y W O R D Scarcinogenesis, pancreatic cancer, PI3K/AKT, TGFβ1, TMEM158

Pancreatic cancer (PC) is the most fatal gastrointestinal malignancy in the world, with a 5‐year relative survival of only 8%. Poly(ADP‐ribose) polymerase (PARP)14, a member of the macro‐PARP subfamily proteins, has been reported to participate in various biologic and pathologic processes in multiple cancers. The roles and underlying molecular mechanisms of PARP14 in PC carcinogenesis, however, remain to be elucidated. In this study, we for the first time discovered that PARP14 was highly expressed in human primary PC specimens and significantly correlated with poor patient prognosis. Using loss‐of‐function studies in vitro and in vivo, we showed that the knockdown of PARP14 led to enhanced apoptosis, repressed proliferation, and gemcitabine (GEM) resistance of PC cells. Further investigations revealed that PARP14 was significantly overexpressed in GEM‐resistant PC cells (SW1990/GZ). And silencing of PARP14 significantly reversed the GEM resistance of SW1990/GZ cells. To the mechanism, PARP14 could stimulate PC progression by the activation of nuclear factor‐κB (NF‐κB) signaling pathway. And inhibition of NF‐κB signal could significantly reverse PARP14–overexpression triggered PC carcinogenesis. In conclusion, PARP14 could promote PC cell proliferation, antiapoptosis, and GEM resistance via NF‐κB signaling pathway, highlighting its potential role as a therapeutic target for PC.