Dataset Information

RON in hepatobiliary and pancreatic cancers: Pathogenesis and potential therapeutic targets.

ABSTRACT: The receptor protein tyrosine kinase RON belongs to the c-MET proto-oncogene family. Research has shown that RON has a role in cancer pathogenesis, which places RON on the frontline of the development of novel cancer therapeutic strategies. Hepatobiliary and pancreatic (HBP) cancers have a poor prognosis, being reported as having higher rates of cancer-related death. Therefore, to combat these malignant diseases, the mechanism underlying the aberrant expression and signaling of RON in HBP cancer pathogenesis, and the development of RON as a drug target for therapeutic intervention should be investigated. Abnormal RON expression and signaling have been identified in HBP cancers, and also act as tumorigenic determinants for HBP cancer malignant behaviors. In addition, RON is emerging as an important mediator of the clinical prognosis of HBP cancers. Thus, not only is RON significant in HBP cancers, but also RON-targeted therapeutics could be developed to treat these cancers, for example, therapeutic monoclonal antibodies and small-molecule inhibitors. Among them, antibody-drug conjugates have become increasingly popular in current research and their potential as novel anti-cancer biotherapeutics will be determined in future clinical trials.

SUBMITTER: Chen SL

PROVIDER: S-EPMC8160627 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

RON in hepatobiliary and pancreatic cancers: Pathogenesis and potential therapeutic targets.

Chen Shao-Long SL Wang Guo-Ping GP Shi Dan-Rong DR Yao Shu-Hao SH Chen Ke-Da KD Yao Hang-Ping HP

World journal of gastroenterology 20210501 20

The receptor protein tyrosine kinase RON belongs to the c-MET proto-oncogene family. Research has shown that RON has a role in cancer pathogenesis, which places RON on the frontline of the development of novel cancer therapeutic strategies. Hepatobiliary and pancreatic (HBP) cancers have a poor prognosis, being reported as having higher rates of cancer-related death. Therefore, to combat these malignant diseases, the mechanism underlying the aberrant expression and signaling of RON in HBP cancer ...[more]

PMID: 34092972

Similar Datasets

Project description:Rhabdoid tumors (RT) are aggressive tumors characterized by genetic loss of SMARCB1 (SNF5, INI-1), a component of the SWI/SNF chromatin remodeling complex. No effective treatment is currently available. This study seeks to shed light on the SMARCB1-mediated pathogenesis of RT and to discover potential therapeutic targets. Global gene expression of 10 RT was compared with 12 cellular mesoblastic nephromas, 16 clear cell sarcomas of the kidney, and 15 Wilms tumors. 114 top genes were differentially expressed in RT (p<0.001, fold change >2 or <0.5). Among these were down-regulation of SMARCB1 and genes previously associated with SMARCB1 (ATP1B1, PTN, DOCK4, NQO1, PLOD1, PTP4A2, PTPRK). 28/114 top differentially expressed genes were involved with neural or neural crest development and were all sharply down-regulated. This was confirmed by Gene Set Enrichment Analysis (GSEA). Neural and neural crest stem cell marker proteins SOX10, ID3, CD133 and Musashi were negative by immunohistochemistry, whereas Nestin was positive. Decreased expression of CDKN1A, CDKN1B, CDKN1C, CDKN2A, and CCND1 was identified, while MYC-C was upregulated. GSEA of independent gene sets associated with bivalent histone modification and polycomb group targets in embryonic stem cells demonstrated significant negative enrichment in RT. Several differentially expressed genes were associated with tumor suppression, invasion and metastasis, including SPP1 (osteopontin), COL18A1 (endostatin), PTPRK, and DOCK4. We conclude that RTs arise within early progenitor cells during a critical developmental window in which loss of SMARCB1 directly results in repression of neural development, loss of cyclin dependent kinase inhibition, and trithorax/polycomb dysregulation. Keywords: Gene expression; rhabdoid tumor; pediatric renal tumors; neural crest The goal of this study is to identify genetic pathways that will clarify the nature of RT and enable the identification of therapeutic targets. Experimental Design: Frozen tissue samples were obtained from the Renal Tumor Bank of the Children's Oncology Group (COG). A total of 53 tumors were hybridized to Affymetrix U133A arrays and analyzed including 10 RT, 12 cellular mesoblastic nephromas (CMN), also known as infantile fibrosarcomas, 16 clear cell sarcomas of the kidney (CCSK) and 15 Wilms tumors (WT). Quality control steps taken: 1. Samples were snap frozen immediately following surgery and were mailed on dry ice to the Tumor Bank and retained at -80Â°C. 2. Frozen sections were evaluated histologically and tumors with less than 80% viable tumor cellularity were excluded. 3. Array images were assessed by eye to confirm scanner alignment and the absence of significant bubbles or scratches. 4. Samples for which the 3'/5' ratios for GAPDH were greater than 3.4 were excluded. 5. The BioB spike controls were confirmed as present 90% of the time; BioC, BioD and cre were confirmed as increasing intensity in all samples. 6. When scaled to a target intensity of 2500, scaling factors were between 13 and 52; background levels were 34-115: Raw Q values were 1.3-3.7 and mean intensities were within acceptable limits. 7. The range of percent present calls was from 30% to 52%. Statistical Analysis: Positional-dependent-nearest-neighbor model (PDNN) software was used to translate the scanned images into expression analysis files and to normalize the data across all arrays (http://odin.mdacc.tmc.edu/~zhangli/PerfectMatch/). To establish a broad list of probesets containing the majority of genes significant in the pathogenesis of RT, the expression of 10 RT was compared with the 43 other tumor types combined (non-RT) using the two-sample t-test, resulting in 2921 probesets with p-value <0.005 and false discovery rate of <1%. This data is provided in the attached supplementary file 'Supplemental Table 1'. To define probesets more uniquely expressed in RT, the gene expression of RT was compared with each of the other tumor types separately (CCSK, CMN, and WT) using the two-sample t-test, and genes present in each one of the resulting four comparisons (RT vs. CCSK, RT vs. CMN, RT vs. WT and RT vs non-RT) with a p-value of <0.001 are provided in the attached supplementary file 'Supplemental Table 2'. Lastly, the 766 genes differentially expressed between RT and non-RT (p<0.0001) were analyzed in PANTHER (Protein ANalysis THrough Evolutionary Relationships), and those groups within the biologic process category over-represented with a Bonferoni corrected p value<0.05 are listed in the attached file labelled âSupplemental Table 3â.

Dataset Information

RON in hepatobiliary and pancreatic cancers: Pathogenesis and potential therapeutic targets.

Publications

RON in hepatobiliary and pancreatic cancers: Pathogenesis and potential therapeutic targets.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets