AQP5 Is a Novel Prognostic Biomarker in Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor with a poor prognosis. The identification of effective molecular markers is of great significance for diagnosis and treatment. Aquaporins (AQPs) are a family of water channel proteins that exhibit several properties and play regulatory roles in human carcinogenesis. However, the association between Aquaporin-5 (AQP5) expression and prognosis and tumor-infiltrating lymphocytes in PAAD has not been reported. AQP5 mRNA expression, methylation, and protein expression data in PAAD were analyzed using GEPIA, UALCAN, HAP, METHSURV, and UCSC databases. AQP5 expression in PAAD patients and cell lines from our cohort was examined using immunohistochemistry and Western blotting. The LinkedOmics database was used to study signaling pathways related to AQP5 expression. TIMER and TISIDB were used to analyze correlations among AQP5, tumor-infiltrating immune cells, and immunomodulators. Survival was analyzed using TCGA and Kaplan-Meier Plotter databases. In this study, we investigated AQP5 expression in PAAD and determined whether the expression of AQP5 is a strong prognostic biomarker for PAAD. We searched and analyzed public cancer databases (GEO, TCGA, HAP, UALCAN, GEPIA, etc.) to conclude that AQP5 expression levels were upregulated in PAAD. Kaplan-Meier curve analysis showed that high AQP5 expression positively correlated with poor prognosis. Using TIMER and TISIDB, we found that the expression of AQP5 was associated with different tumor-infiltrating immune cells, especially macrophages. We found that hypomethylation of the AQP5 promoter region was responsible for its high expression in PAAD. AQP5 can serve as a novel biomarker to predict prognosis and immune infiltration in PAAD.

Chen G ，Song H ，Yang Z ，Du T ，Zheng Y ，Lu Z ，Zhang K ，Wei D ... -  《Frontiers in Oncology》

High expression of RNF169 is associated with poor prognosis in pancreatic adenocarcinoma by regulating tumour immune infiltration.

Background: Pancreatic adenocarcinoma (PAAD) is a highly deadly and aggressive tumour with a poor prognosis. However, the prognostic value of RNF169 and its related mechanisms in PAAD have not been elucidated. In this study, we aimed to explore prognosis-related genes, especially RNF169 in PAAD and to identify novel potential prognostic predictors of PAAD. Methods: The GEPIA and UALCAN databases were used to investigate the expression and prognostic value of RNF169 in PAAD. The correlation between RNF169 expression and immune infiltration was determined by using TIMER and TISIDB. Correlation analysis with starBase was performed to identify a potential regulatory axis of lncRNA-miRNA-RNF169. Results: The data showed that the level of RNF169 mRNA expression in PAAD tissues was higher than that in normal tissues. High RNF169 expression was correlated with poor prognosis in PAAD. In addition, analysis with the TISIDB and TIMER databases revealed that RNF169 expression was positively correlated with tumour immune infiltration in PAAD. Correlation analysis suggested that the long non-coding RNA (lncRNA) AL049555.1 and the microRNA (miRNA) hsa-miR-324-5p were involved in the expression of RNF169, composing a potential regulatory axis to control the progression of PAAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that RNF169 plays a role in PAAD through pathways such as TNF, Hippo, JAK-STAT and Toll-like receptor signaling. Conclusion: In summary, the upregulation of RNF169 expression mediated by ncRNAs might influence immune cell infiltration in the microenvironment; thus, it can be used as a prognostic biomarker and a potential therapeutic target in PAAD.

Wang J ，Chen H ，Deng Q ，Chen Y ，Wang Z ，Yan Z ，Wang Y ，Tang H ，Liang H ，Jiang Y ... -  《Frontiers in Genetics》

Unraveling the role of Major Vault Protein as a novel immune-related biomarker that promotes the proliferation and migration in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a formidable challenge in oncology research, with a complex pathogenesis that requires to be explored. Major Vault Protein (MVP) is the principal structural component of the vault complex, and its expression level is remarkably upregulated in various cancers. Extensive investigations have been conducted to explore the role of MVP in specific cancer contexts, yet the potential molecular mechanisms and biological functions of MVP in PAAD still remain considerably elusive. This study aims to explore the role of MVP as a novel immune-related biomarker in the pathogenesis and clinical treatment of PAAD. Gene expression data and clinical information were collected from TCGA, GTEx and GEO databases. Survival, prognostic and functional enrichment analysis were employed with R software. Immunological correlation analysis was performed using TIMER2.0, TIDE scores, TISIDB and TISCH. Epigenetic analysis was implemented by MethSurv, CPTAC, UALCAN, and cBioPortal. Drug analysis was conducted using Enrichr and CellMiner. Moreover, cellular experiments, like RNA interference, qRT-PCR, Western blot, cell cycle analysis, cell apoptosis analysis, colony formation assay, transwell assay, and wound healing assay, were performed for verifying the functional properties of MVP in the PAAD progression. We demonstrated an abnormally upregulated expression of MVP in PAAD tissues, which notably correlated with an adverse prognosis in PAAD patients. Functional analysis suggested the conceivable involvement of MVP in immune modulation, and immunotherapy. Additionally, we identified genetic alterations, reduced promoter methylation, and heightened phosphorylation in MVP. We also clarified Suloctidil and Tetradioxin as the most notable potential drugs targeting MVP in PAAD. Moreover, our experimental observations consistently highlighted the significant impact of MVP deficiency on impeding PAAD cell proliferation, inhibiting cell migration, and accelerating cell apoptosis. Interestingly, a potential link between MVP and ERK or AKT pathways was displayed, which opens new avenues for further exploration of the molecular mechanisms of MVP-targeted therapies in PAAD. This study systematically describes MVP as an immune-related biomarker with remarkable potential for predicting the prognosis, tumor progression and immunotherapeutic efficacy in PAAD.

Wu X ，Hao L ，Lin J ，Guo X ，Luo Y ，Li C ... -  《-》

Bioinformatics analysis identified MMP14 and COL12A1 as immune-related biomarkers associated with pancreatic adenocarcinoma prognosis.

Li Y ，Su Z ，Wei B ，Qin M ，Liang Z ... -  《-》

CHST12: a potential prognostic biomarker related to the immunotherapy response in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is characterized by lower immunogenicity with a poor response rate to immune checkpoint inhibitors (ICIs) and exhibits the poorest prognosis of all solid tumors, which results in the highest tumor-related mortality among malignancies. However, the underlying mechanisms are poorly understood. In addition, diverse carbohydrate sulfotransferases (CHSTs), which are involved in the sulfation process of these structures, play an important role in the metastatic spread of tumor cells. Aberrant glycosylation is beginning to emerge as an influencing factor in tumor immunity and immunotherapy. Therefore, it might serve as a biomarker of the immunotherapeutic response in tumors. The purpose of the study was to evaluate the role of CHST12 in PAAD prognosis and its relevance to the immunotherapeutic response. A comprehensive investigation of the interactions between CHST12 expression and the immune microenvironment as well as the clinical significance of CHST12 in PAAD was conducted. Data derived from the Cancer Genome Atlas (TCGA) database were analyzed using univariate and multivariate approaches, the Tumor Immune Estimation Resource (TIMER), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms. Publicly available datasets were analyzed in this study. These data can be found on websites such as http://www.xiantao.love and https://www.proteinatlas.org. An assessment of the predictive value of CHST12 for PAAD prognosis was conducted using univariate and multivariate Cox regression analysis, Kaplan-Meier analysis, and nomograms. The TIMER algorithm calculates the proportions of six types of immune cells. The TIDE algorithm was used to indicate the characteristics of tumors that respond to ICI therapy. The mRNA and protein levels of CHST12 showed the opposite trend. CHST12 mRNA expression was significantly upregulated in PAAD. According to Cox regression analysis, CHST12 RNA expression acts as a protective factor for overall survival [hazard ratio (HR), 0.617, P < 0.04]. Functional annotation indicated that CHST12-associated differentially expressed genes (DEGs) were related to the signaling activity of receptor tyrosine kinases and the regulation of ubiquitin-protein transferase. These are usually involved in tumor development and may be related to the treatment responses of immune checkpoint inhibitors (ICIs). There was significantly higher CHST12 mRNA expression in PAAD samples than in non-malignant samples. In PAAD, elevated CHST12 mRNA expression might regulate immune cell infiltration into the tumor microenvironment (TME) and may predict clinical outcomes.

Liu K ，Li L ，Han G 《-》