Substantial alterations at the multi-omics level of pancreatic cancer (PC) impede the possibility to diagnose and treat patients in early stages. Herein, we conducted an integrative omics-based translational analysis, utilizing next-generation sequencing, transcriptome meta-analysis, and immunohistochemistry, combined with statistical learning, to validate multiplex biomarker candidates for the diagnosis, prognosis, and management of PC. Experiment-based validation was conducted and supportive evidence for the essentiality of the candidates in PC were found at gene expression or protein level by practical biochemical methods. Remarkably, the random forests (RF) model exhibited an excellent diagnostic performance and LAMC2, ANXA2, ADAM9, and APLP2 greatly influenced its decisions. An explanation approach for the RF model was successfully constructed. Moreover, protein expression of LAMC2, ANXA2, ADAM9, and APLP2 was found correlated and significantly higher in PC patients in independent cohorts. Survival analysis revealed that patients with high expression of ADAM9 (Hazard ratio (HR)_OS = 2.2, p-value < 0.001), ANXA2 (HR_OS = 2.1, p-value < 0.001), and LAMC2 (HR_DFS = 1.8, p-value = 0.012) exhibited poorer survival rates. In conclusion, we successfully explore hidden biological insights from large-scale omics data and suggest that LAMC2, ANXA2, ADAM9, and APLP2 are robust biomarkers for early diagnosis, prognosis, and management for PC.

Radiosensitization of the PI3K inhibitor HS-173 through reduction of DNA damage repair in pancreatic cancer Radiosensitization of the PI3K inhibitor HS-173 through reduction of DNA damage repair in pancreatic cancer

Park YH, et al. J Korean Med Sci. 2016 Feb;31(2):208-213. http://dx.doi.org/10.3346/jkms.2016.31.2.208

Epithelial mesenchymal transition (EMT) has an important role in invasion and metastasis of tumor cells. The purpose of this study was to evaluate the roles of EMT-associated proteins on progression and metastasis as a prognostic/predictive factor in curatively-resected (R0) head and neck squamous cell carcinoma (HNSCC). A total of 118 patients who received curative surgery for HNSCC at Inha University Hospital between January 1996 and December 2011 were included. We used protein immunohistochemistry to evaluate the expression of E-cadherin, vimentin, and EZH2 on tissue microarrays. Also, we reviewed all medical records and analyzed the relationship between the expression of EMT-associated proteins and prognosis. The E-cadherin-negative group showed more moderate/poor differentiation of cancer cell type than the higher E-cadherin-expressing group (p=.016) and high EZH2 expression was significantly correlated with nodal metastasis (p=.012). Our results demonstrate a significant association between high expression of EZH2 and vimentin and presence of distant progression (p=.026). However, expression of E-cadherin, vimentin, and EZH2 was not significantly associated with overall survival. These findings suggest that an EMT-associated protein expression profile is correlated with aggressiveness of disease and prognosis, and could be a useful marker for determination of additional treatment in curatively-resected HNSCC patients.

Ha H, et al. Brain Tumor Res Treat. 2022 Jul;10(3):158-163. https://doi.org/10.14791/btrt.2022.0018