Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer with an abysmal prognosis rate over the last few decades. Early diagnosis and prevention could effectively combat this malignancy. Therefore, it is crucial to discover potential biomarkers to identify asymptomatic premalignant or early malignant tumors of PDAC. Gene expression analysis is a powerful technique to identify candidate biomarkers involved in disease progression. In the present study, five independent gene expression datasets, including 321 PDAC tissues and 208 adjacent non-cancerous tissue samples, were subjected to statistical and bioinformatics analysis. A total of 20 differentially expressed genes (DEGs) were identified in PDAC tissues compared to non-cancerous tissue samples. Gene ontology and pathway enrichment analysis showed that DEGs were mainly enriched in extracellular matrix (ECM), cell adhesion, ECM–receptor interaction, and focal adhesion signaling. The protein–protein interaction network was constructed, and the hub genes were evaluated. Collagen type XII alpha 1 chain (COL12A1), fibronectin 1 (FN1), integrin subunit alpha 2 (ITGA2), laminin subunit beta 3 (LAMB3), laminin subunit gamma 2 (LAMC2), thrombospondin 2 (THBS2), and versican (VCAN) were identified as hub genes. The correlation analysis revealed that identified hub genes were significantly interconnected. Wherein COL12A1, FN1, ITGA2, LAMB3, LAMC2, and THBS2 were significantly associated with PDAC pathological stages. The Kaplan–Meier survival plots revealed that ITGA2, LAMB3, and LAMC2 expression were inversely correlated with a prolonged patient survival period. Furthermore, the Human Protein Atlas database was used to validate the expression and cellular origins of hub genes encoded proteins. The protein expression of hub genes was higher in pancreatic cancer tissue than in normal pancreatic tissue samples, wherein ITGA2, LAMB3, and LAMC2 were exclusively expressed in pancreatic cancer cells. Pancreatic cancer cell-specific expression of these three proteins may play pleiotropic roles in cancer progression. Our results collectively suggest that ITGA2, LAMB3, and LAMC2 could provide deep insights into pancreatic carcinogenesis molecular mechanisms and provide attractive therapeutic targets.

Although epidemiological studies have shown a relationship between periodontal disease and pancreatic cancer, the molecular mechanisms involved remain unclear. In this study, the effects of systemic administration of Porphyromonas gingivalis lipopolysaccharide (PG-LPS) on gene expression were comprehensively explored in mouse pancreas that did not demonstrate any signs of inflammation. PG-LPS was prepared in physiological saline and intraperitoneally administered to male mice at a concentration of 5 mg/kg every 3 days for 1 month. After extracting total RNA from the excised mice pancreas, a comprehensive DNA microarray analysis of gene expression was performed. Tissue specimens were also subjected to hematoxylin–eosin staining and immunohistochemistry using anti-regenerating islet-derived 3A and G (Reg3A/G) antibody. ImageJ software was used to quantify the area of Reg3A/G positive cells in pancreatic islets by binarizing image date followed by area extraction. The results were compared using Mann–Whitney U test. Data are presented as mean ± standard deviation (SD) with p < 0.05 considered as significant. Reg3G, a gene related to pancreatic cancer, was one of the 10 genes with the highest levels of expression in the pancreas stimulated with PG-LPS. The comprehensive analysis revealed a 73-fold increase in Reg3G expression level in the PG-LPS group when compared with the control group; in addition, the expression level of Reg3A was increased by 11-fold in the PG-LPS group. Image analysis showed that the ratio of Reg3A/G positive cells was higher in the PG-LPS group than the control. Immunostaining showed the presence of Reg3A/G-positive cells in the alpha-cell equivalent areas around the islets of Langerhans in the PG-LPS group. These results support the notion that periodontal disease may be a risk factor for pancreatic cancer.

Background/Aim: Cancer is the most fatal disease worldwide whose most lethal characteristics are invasion and metastasis. Hepatocellular carcinoma (HCC) is one of the most fatal cancers worldwide. HCC often shows encapsulation, which is related to better prognosis. In this study, proteomic analysis of HCC tissues with and without encapsulation was performed, in order to elucidate the factors which play important roles in encapsulation. Materials and Methods: Five HCC tissues surrounded by a capsule and five HCC tissues which broke the capsule were obtained from patients diagnosed with HCC who underwent surgical liver resection. Protein samples from these tissues were separated by two-dimensional gel electrophoresis (2-DE), and the protein spots whose expression was different between encapsulated and non-encapsulated HCC tissues were identified through gel imaging analysis software. The selected protein spots were analyzed and identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Two-DE analysis showed 14 spots whose expression was different between encapsulated and non-encapsulated HCC tissues. Of these, 9 were up-regulated and 5 were down-regulated in HCC tissues without encapsulation. The validation by Western blot confirmed that leucine aminopeptidase 3 (LAP3) and phosphoenolpyruvate carboxykinase mitochondrial (PCK2) were up-regulated significantly in HCC tissues with a capsule, compared to HCC tissues that broke the capsule. Conclusion: These findings suggest that LAP3 and PCK2 could be factors responsible for the maintenance of encapsulation in HCC tissues.

Background/Aim: We have previously reported that treatment of pancreatic cancer cells with active hexose-correlated compound (AHCC), an extract of a basidiomycete mushroom, decreases the levels of tumor-associated proteins including heat-shock protein 27 (HSP27), heat shock factor 1 (HSF1) and sex-determining region Y-box 2 (SOX2). The transmembrane glycoprotein, CUB domain-containing protein 1 (CDCP1) has been reported to be up-regulated in various cancers, and be associated with invasion and metastasis. The aim of this study was to examine the effect of AHCC on the expression of CDCP1 in KLM1-R cells. Materials and Methods: Gemcitabine-resistant pancreatic cancer cells (KLM1-R) were treated with AHCC (10 mg/ml) for 48 h. Western blot analysis of cell extracts with anti-CDCP1 or anti-actin antibodies was performed to assess the expression of CDCP1. Results: Expression of CDCP1 was reduced by AHCC treatment of KLM1-R cells, whereas expression of actin was not affected. The ratio of intensities of CDCP1/actin in AHCC-treated KLM1-R cells was significantly suppressed (p<0.05) compared to untreated cells. Conclusion: AHCC down-regulated CDCP1 expression and inhibited the malignant progression of pancreatic cancer cells.

Background/Aim: Uveal melanoma is one of the most common primary intraocular tumors. It arises from melanocytes in the uvea and accounts for 3-5% of all melanomas. Uveal melanoma has a high metastatic potential. About half of the patients develop distant metastases including the liver, and the median survival time has been reported to be 4-5 months. Although the primary treatment for uveal melanoma has evolved from enucleation to eye-saving local treatment, there is no impact on the occurrence of distant metastases or overall survival. At least 50% of patients will develop metastases and the 3-year survival rate drops rapidly to 13%. Therefore, it is important to find prognostic biomarkers and therapeutic molecular targets that improve survival in patients with uveal melanoma. DDX39 is an Asp-Glu-Ala-Asp (DEAD) box RNA helicase required for mRNA transcription, splicing, and transport. There have been several reports of DDX39 over-expression in tumor tissues and cells, and we reported that patients with adrenocortical carcinoma with high DDX39 expression had a significantly worse prognosis. The clinicopathological involvement of DDX39 in uveal melanoma has not yet been documented. Materials and Methods: We analyzed DDX39 mRNA expression and survival in patients with uveal melanoma using the GEPIA2 and UALCAN platforms. Results: DDX39 was found to be up-regulated in uveal melanoma tissues with increasing stage, and this up-regulated expression was inversely correlated with prolonged patient survival. Conclusion: DDX39 may be one of the potential prognostic biomarkers for patients with uveal melanoma.

Background/Aim: Uveal melanoma (UVM) is the most prevalent primary intraocular malignancy, accounting for 3-5% of all melanomas. Despite its rarity, particularly in Japan (~2 cases per 100,000 individuals annually), UVM exhibits highly aggressive behavior, with nearly 50% of patients developing distant metastases. Once metastasized, the prognosis remains dismal, with a median survival of only 4-5 months. Identifying prognostic biomarkers and potential therapeutic targets is imperative to improve clinical outcomes. Stanniocalcin-1 (STC-1) is a glycoprotein hormone implicated in calcium and phosphate homeostasis. Recent studies have linked STC-1 overexpression to tumor progression, poor prognosis, and increased metastatic potential in various malignancies. However, the prognostic significance and mechanistic role of STC-1 in UVM remain unexplored. Materials and Methods: To elucidate the clinical relevance of STC-1 in UVM, we analyzed publicly available transcriptomic datasets using GEPIA2 and UALCAN, assessing STC-1 mRNA expression across disease stages and its correlation with patient survival. In parallel, single-cell RNA sequencing (scRNA-seq) datasets were utilized to identify the cellular sources of STC-1 within the UVM tumor microenvironment and to investigate its association with specific functional cellular states. Results: STC-1 expression was significantly up-regulated in stage IV UVM tumors compared to stage III (n=4 and 36, respectively). Moreover, elevated STC-1 expression was inversely correlated with overall survival, suggesting its potential role in disease progression. scRNA-seq analysis revealed that STC-1 is expressed by both tumor cells and fibroblasts, indicating a possible cooperative mechanism that may drive tumor progression. Conclusion: These findings suggest that STC-1 serves as a potential prognostic biomarker in UVM, providing novel insights into its role in tumor biology. Further investigation is warranted to explore its therapeutic implications and mechanistic contributions to UVM progression.