Preclinical assesement of survivin and XIAP as prognostic biomarkers and therapeutic targets in gastroenteropancreatic neuroendocrine neoplasia

Abstract Background The molecular prognostic biomarkers of clear cell renal cell carcinoma (ccRCC) are still unknown. We aimed at researching the candidate biomarkers and potential therapeutic targets of ccRCC. Methods Three ccRCC expression microarray datasets (include GSE14762, GSE66270 and GSE53757) were downloaded from the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) between ccRCC and normal tissues were explored. The potential functions of identified DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). And then the protein - protein interaction network (PPI) was established to screen the hub genes. After that, the expressions of hub genes were identified by the oncomine database. The hub genes’ prognostic values of patients with ccRCC were analyzed by GEPIA database. Results A total of 137 DEGs were identified by utilizing the limma package and RRA method, including 63 upregulated genes and 74 downregulated genes. It is found that 137 DEGs were mainly enriched in 82 functional terms and 24 pathways in accordance with the research results. Thirteen highest-scoring genes were screened as hub genes (include 10 upregulated genes and 3 downregulated candidate genes) by utilizing the PPI network and module analysis. Through integrating the oncoming database and GEPIA database, the author found that C3 and CXCR4 are not only overexpressed in ccRCC, but also associated with the prognosis of ccRCC. Further results could reveal that patients with high C3 expression had a poor overall survival (OS), while patients with high CTSS and TLR3 expressions had a good OS; patients with high C3 and CXCR4 expressions had a poor disease-free survival (DFS), while ccRCC patients with high TLR3 expression had a good DFS. Conclusion These findings suggested that C3 and CXCR4 were the candidate biomarkers and potential therapeutic targets of ccRCC patients.

Download Full-text

Predictive and prognostic biomarkers with therapeutic targets in colorectal cancer: A 2021 update on current development, evidence, and recommendation

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211005525 ◽

2021 ◽

pp. 107815522110055

Author(s):

Clement Chung

Keyword(s):

Checkpoint Inhibitors ◽

Therapeutic Targets ◽

Growth Factor Receptor ◽

Predictive Biomarkers ◽

Tumor Location ◽

Prognostic Biomarkers ◽

Her2 Gene ◽

Braf Mutations ◽

Therapeutic Implications ◽

Molecular Alterations

Although therapeutically actionable molecular alterations are widely distributed across many cancer types, only a handful of them show evidence of clinical utility and are recommended for routine clinical practice in the management of cancers of colon and rectum (CRC). This 2021 update aims to provide a succinct summary on the use of prognostic and/or predictive biomarkers (expanded RAS, BRAF, microsatellite-high [MSI-H] or deficient mismatch repair [dMMR], neurotrophic tyrosine receptor kinase [ NTRK] fusion genes, and human epidermal growth factor receptor type II [ HER2] gene amplification) associated with CRC. Therapeutic implications of each relevant predictive or prognostic biomarker for patients with CRC are described, along with discussion on new developments on (1) biomarker-driven therapies such as testing of BRAF, MLH1 promoter methylation and MMR germline genes in differentiating sporadic CRC or hereditary conditions such as Lynch syndrome; (2) first-line use of immune checkpoint inhibitors in metastatic CRC; (3) risk stratification and therapy selection based on primary tumor location (left-sided vs. right-sided colon cancer); (3) atypical BRAF mutations; (4) use of EGFR directed therapy in the perioperative oligometastatic disease setting; (5) re-challenge of EGFR directed therapy and (6) personalizing therapy of fluoropyrimidine and irinotecan based on new evidence in pharmacogenomic testing. Data are collected and analyzed from available systematic reviews and meta-analyses of treatments with known therapeutic targets in CRC, which may be associated with predictive and/or prognostic biomarkers. Discussions are presented in an application-based format, with goal to empower pharmacists or other clinicians to gain awareness and understanding in biomarker-driven cancer therapy issues.

Download Full-text

COL6A2/3 can serve as potential therapeutic targets and prognostic biomarkers for clear cell renal cell carcinoma

10.21203/rs.3.rs-119445/v1 ◽

2020 ◽

Author(s):

Wingkeung Yiu ◽

Can-Xuan Li ◽

Jie Chen

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Mrna Expression ◽

Renal Cell ◽

Clear Cell ◽

Therapeutic Targets ◽

Gene Set Enrichment Analysis ◽

Prognostic Biomarkers ◽

Cell Renal Cell Carcinoma ◽

Tumorigenesis And Progression

Abstract Background: Growing evidence has shown that the type VI collagen alpha chain (COL6A) family involved in the tumorigenesis and progression of diverse malignancies; however, its biological roles and potential mechanisms in clear cell renal cell carcinoma (ccRCC) remain unknown. The study was designed to explore the potential mechanisms and functions of COL6As in ccRCC.Methods: ONCOMINE and GEPIA databases were used to compare the transcriptional expression data of COL6As in ccRCC samples and normal renal samples. UALCAN database was utilized to determine the association between clinicopathological features and COL6As expression. Kaplan–Meier method was employed to determine the prognostic value of COL6As mRNA expression in ccRCC. CBioPortal database was used to investigate the genetic alterations of COL6As in ccRCC. Co-expression analyses, functional enrichment analyses, and gene set enrichment analysis (GSEA) were utilized to explore the potential action mechanisms of COL6As in ccRCC. Finally, we estimated the relationship between COL6As expression with immune cell infiltrates.Results: Upregulated transcriptional COL6A2/COL6A3 expression was observed in ccRCC specimens by comparison with noncancerous renal specimens. Patients with increased COL6A2/COL6A3 mRNA expression have a poor clinical outcome and unfavorable prognosis. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA analyses showed that COL6A2/COL6A3 might promote the tumorigenesis and progression of ccRCC by involving in several cancer-related pathways, such as axon guidance, focal adhesion, ECM receptor interaction. Besides, we found that COL6A2/COL6A3 expression was significantly associated with immune infiltration levels in ccRCC.Conclusions: COL6A2 and COL6A3 could act as candidate prognostic biomarkers and therapeutic targets in ccRCC. However, further experimental work was required to validate the conclusions.

Download Full-text

Aberrant RON and MET Co-overexpression as Novel Prognostic Biomarkers of Shortened Patient Survival and Therapeutic Targets of Tyrosine Kinase Inhibitors in Pancreatic Cancer

Frontiers in Oncology ◽

10.3389/fonc.2019.01377 ◽

2019 ◽

Vol 9 ◽

Cited By ~ 3

Author(s):

Chen-Yu Hu ◽

Xiang-Ming Xu ◽

Bo Hong ◽

Zhi-Gang Wu ◽

Yun Qian ◽

...

Keyword(s):

Pancreatic Cancer ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitors ◽

Kinase Inhibitors ◽

Patient Survival ◽

Therapeutic Targets ◽

Prognostic Biomarkers

Download Full-text

Ca2+-Binding Proteins of the EF-Hand Superfamily: Diagnostic and Prognostic Biomarkers and Novel Therapeutic Targets

Methods in Molecular Biology - Calcium-Binding Proteins of the EF-Hand Superfamily ◽

10.1007/978-1-4939-9030-6_11 ◽

2019 ◽

pp. 157-186 ◽

Cited By ~ 10

Author(s):

Claus W. Heizmann

Keyword(s):

Binding Proteins ◽

Therapeutic Targets ◽

Prognostic Biomarkers ◽

Ef Hand ◽

Novel Therapeutic

Download Full-text

Abstract 3321: Dysregulation of m6A RNA methylation regulators in colorectal cancer: Clinical implication as prognostic biomarkers and potential therapeutic targets

10.1158/1538-7445.am2018-3321 ◽

2018 ◽

Author(s):

Raju Kandimalla ◽

Feng Gao ◽

Chun Ruan ◽

Michael Hsieh ◽

Xin Wang ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Implication ◽

Therapeutic Targets ◽

Prognostic Biomarkers ◽

Rna Methylation ◽

M6a Rna Methylation

Download Full-text

Mining database for the therapeutic targets and prognostic biomarkers among STAT family in glioblastoma

Cancer Biomarkers ◽

10.3233/cbm-201746 ◽

2020 ◽

pp. 1-13

Author(s):

Chenglin Li ◽

Yanfei Zhou ◽

Hanshun Deng ◽

Yuanshen Ye ◽

Shuizhen Zhao ◽

...

Keyword(s):

Immune Response ◽

Signaling Pathway ◽

Web Applications ◽

Therapeutic Targets ◽

Prognostic Biomarkers ◽

Receptor Interaction ◽

Immune Gene ◽

Nf Kappa B ◽

Signal Transducers ◽

Pathways Analysis

BACKGROUND: Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with a high mortality rate. Aberrant activation of signal transducers and activators of transcription (STAT) signaling results in tumor pathogenesis and progression by regulating cell cycle, cell survival and immune response. METHODS: Therapeutic targets and prognostic biomarkers within the STAT family in GBM were explored using web applications and databases. RESULTS: High levels of STAT1/3/5A/5B/6 and low levels of STAT4 were observed in GBM patients. GBM patients expressing high STAT1/2/3/5A/6 and low STAT4/5B levels had the worse overall survival. Among the STAT family, STAT4 and STAT6 were the most frequently mutated genes. A low to moderate correlation among members of the STAT family was observed. Additionally, the STATs were involved in activation or inhibition of cancer related pathways. Analysis of immune infiltrates showed STAT5A levels to be significantly correlated with abundance of immune cells and levels of immune gene biomarkers. Gene ontology (GO) functions and KEGG pathway analysis indicated that STAT5A is involved in immune response-regulating signaling pathway, neutrophil and lymphocyte mediated immunity, single-stranded DNA binding, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway. Moreover, several kinase and transcription factor targets of STAT5A in GBM were identified. CONCLUSION: We report here therapeutic targets, prognostic biomarkers and regulation network of STAT family in GBM. These findings lay a foundation for further studies on the role of STAT family in therapy and prognosis of GBM. Further studies are required to verify our results.

Download Full-text