RGD Reference Report - Comprehensive molecular characterization of inhibitors of apoptosis proteins (IAPs) for therapeutic targeting in cancer. - Rat Genome Database

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Comprehensive molecular characterization of inhibitors of apoptosis proteins (IAPs) for therapeutic targeting in cancer.

Authors: Liang, Jianfeng  Zhao, Wanni  Tong, Pan  Li, Ping  Zhao, Yuanli  Li, Hua  Liang, Jun 
Citation: Liang J, etal., BMC Med Genomics. 2020 Jan 21;13(1):7. doi: 10.1186/s12920-020-0661-x.
RGD ID: 153344516
Pubmed: PMID:31964418   (View Abstract at PubMed)
PMCID: PMC6975060   (View Article at PubMed Central)
DOI: DOI:10.1186/s12920-020-0661-x   (Journal Full-text)


BACKGROUND: Inhibitors of apoptosis proteins (IAPs) are a family of antiapoptotic proteins modulating cell cycle, signal transduction and apoptosis. Dysregulated IAPs have been reported to contribute to tumor progression and chemoresistance in various cancers. However, existing studies were sporadic and only focus on one specific cancer with one particular gene in the IAPs family. A systematic investigation on the co-expression pattern, regulation frameworks on various pathways, prognostic utility on patient outcomes, and predictive value on drug sensitivity among all the IAPs across multiple tumor types was lacking.
METHODS: Leveraging The Cancer Genome Atlas data with comprehensive genomic characterizations on 9714 patients across 32 tumor types and the Genomics of Drug Sensitivity in Cancer data with both genomic characterizations and drug sensitivity data on > 1000 cell lines, we investigated the co-expression pattern of IAPs, their regulations of apoptosis as well as other pathways and clinical relevance of IAPs for therapeutics development.
RESULTS: We discovered diverse expression pattern among IAPs, varied spectrum of apoptosis regulations through IAPs and extensive regulations beyond apoptosis involving immune response, cell cycle, gene expression and DNA damage repair. Importantly, IAPs were strong prognostic factors for patient survival and tumor stage in several tumor types including brain, liver, kidney, breast and lung cancer. Further, several IAPs were found to be predictive of sensitivity to BCL-2 inhibitors (BIRC3, BIRC5, BIRC6, and BIRC7) as well as RIPK1 inhibitors (BIRC3 and BIRC6).
CONCLUSION: Together, our work revealed the landscape of regulations, prognostic utilities and therapeutic relevance of IAPs across multiple tumor types.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BIRC2Humanadrenocortical carcinoma exacerbatesHEP mRNA:increased expression:adrenal gland (human)RGD 
BIRC3Humanadrenocortical carcinoma amelioratesHEP mRNA:increased expression:adrenal gland (human)RGD 
BIRC5Humanadrenocortical carcinoma exacerbatesHEP mRNA:increased expression:adrenal gland (human)RGD 
BIRC6Humanadrenocortical carcinoma exacerbatesHEP mRNA:increased expression:adrenal gland (human)RGD 
BIRC7Humanadrenocortical carcinoma amelioratesHEP mRNA:increased expression:adrenal gland (human)RGD 
XIAPHumanadrenocortical carcinoma amelioratesHEP mRNA:increased expression:adrenal gland (human)RGD 
BIRC5Humanbladder urothelial carcinoma disease_progressionHEP mRNA:increased expression:urinary bladder (human)RGD 
BIRC7Humanbladder urothelial carcinoma disease_progressionHEP mRNA:increased expression:urinary bladder (human)RGD 
BIRC3Humanbrain glioma exacerbatesHEP mRNA:increased expression:brain (human)RGD 
BIRC5Humanbrain glioma exacerbatesHEP mRNA:increased expression:brain (human)RGD 
NAIPHumanbrain glioma exacerbatesHEP mRNA:increased expression:brain (human)RGD 
BIRC3Humanbreast carcinoma amelioratesHEP mRNA:increased expression:breast (human)RGD 
BIRC5Humanbreast carcinoma exacerbatesHEP mRNA:increased expression:breast (human)RGD 
BIRC7Humanbreast carcinoma disease_progressionHEP mRNA:increased expression:breast (human)RGD 
NAIPHumanbreast carcinoma disease_progressionHEP mRNA:decreased expression:breast (human)RGD 
XIAPHumanbreast carcinoma exacerbatesHEP mRNA:increased expression:breast (human)RGD 
BIRC6Humancholangiocarcinoma amelioratesHEP mRNA:increased expression:bile duct (human)RGD 
BIRC5Humanchromophobe renal cell carcinoma exacerbatesHEP mRNA:increased expression:kidney (human)RGD 
BIRC3Humanclear cell renal cell carcinoma disease_progressionHEP mRNA:increased expression:kidney (human)RGD 
BIRC5Humanclear cell renal cell carcinoma exacerbatesHEP mRNA:increased expression:kidney (human)RGD 
BIRC6Humanclear cell renal cell carcinoma amelioratesHEP mRNA:increased expression:kidney (human)RGD 
XIAPHumanclear cell renal cell carcinoma amelioratesHEP mRNA:increased expression:kidney (human)RGD 
NAIPHumancolon adenocarcinoma exacerbatesHEP mRNA:increased expression:colon (human)RGD 
BIRC7Humanesophageal carcinoma disease_progressionHEP mRNA:increased expression:esophagus (human)RGD 
BIRC2Humangastric adenocarcinoma exacerbatesHEP mRNA:increased expression:stomach (human)RGD 
BIRC3Humangastric adenocarcinoma disease_progressionHEP mRNA:increased expression:stomach (human)RGD 
BIRC7Humangastric adenocarcinoma exacerbatesHEP mRNA:increased expression:stomach (human)RGD 
NAIPHumangastric adenocarcinoma disease_progressionHEP mRNA:increased expression:stomach (human)RGD 
XIAPHumangastric adenocarcinoma disease_progressionHEP mRNA:increased expression:stomach (human)RGD 
BIRC3Humanglioblastoma exacerbatesHEP mRNA:increased expression:brain (human)RGD 
BIRC2Humanhead and neck squamous cell carcinoma exacerbatesHEP mRNA:increased expression:head or neck skin (human)RGD 
BIRC3Humanhead and neck squamous cell carcinoma amelioratesHEP mRNA:increased expression:head or neck skin (human)RGD 
NAIPHumanhead and neck squamous cell carcinoma amelioratesHEP mRNA:increased expression:head or neck skin (human)RGD 
BIRC5Humanhepatocellular carcinoma disease_progressionHEP mRNA:increased expression:liver (human)RGD 
BIRC7Humanhepatocellular carcinoma exacerbatesHEP mRNA:increased expression:liver (human)RGD 
BIRC5Humanlung adenocarcinoma amelioratesHEP mRNA:increased expression:lung (human)RGD 
BIRC5Humanlung adenocarcinoma disease_progressionHEP mRNA:increased expression:lung (human)RGD 
NAIPHumanlung adenocarcinoma amelioratesHEP mRNA:increased expression:lung (human)RGD 
BIRC5Humanlung squamous cell carcinoma disease_progressionHEP mRNA:increased expression:lung (human)RGD 
BIRC6Humanlung squamous cell carcinoma disease_progressionHEP mRNA:increased expression:lung (human)RGD 
BIRC3HumanMesothelioma amelioratesHEP mRNA:increased expression:mesothelium (human)RGD 
BIRC5HumanMesothelioma exacerbatesHEP mRNA:increased expression:mesothelium (human)RGD 
XIAPHumanMesothelioma amelioratesHEP mRNA:increased expression:mesothelium (human)RGD 
BIRC3Humanovarian serous cystadenocarcinoma exacerbatesHEP mRNA:increased expression:ovary (human)RGD 
BIRC2Humanpancreatic adenocarcinoma exacerbatesHEP mRNA:increased expression:pancreas (human)RGD 
BIRC3Humanpancreatic adenocarcinoma disease_progressionHEP mRNA:increased expression:pancreas (human)RGD 
BIRC5Humanpancreatic adenocarcinoma exacerbatesHEP mRNA:increased expression:pancreas (human)RGD 
BIRC7Humanpancreatic adenocarcinoma exacerbatesHEP mRNA:increased expression:pancreas (human)RGD 
BIRC3Humanpapillary renal cell carcinoma exacerbatesHEP mRNA:increased expression:kidney (human)RGD 
BIRC5Humanpapillary renal cell carcinoma disease_progressionHEP mRNA:increased expression:kidney (human)RGD 
XIAPHumanpapillary renal cell carcinoma exacerbatesHEP mRNA:increased expression:kidney (human)RGD 
BIRC2Humanparaganglioma exacerbatesHEP mRNA:increased expression:adrenal gland and chromaffin cell (human)RGD 
NAIPHumanparaganglioma exacerbatesHEP mRNA:increased expression:adrenal gland and chromaffin cell (human)RGD 
BIRC6Humanprostate adenocarcinoma amelioratesHEP mRNA:increased expression:prostate gland (human)RGD 
BIRC7Humanprostate adenocarcinoma exacerbatesHEP mRNALincreased expression:prostate gland (human)RGD 
BIRC2Humanrectum adenocarcinoma disease_progressionHEP mRNA:increased expression:rectum (human)RGD 
BIRC3Humanrectum adenocarcinoma amelioratesHEP mRNA:increased expression:rectum (human)RGD 
BIRC2Humanskin melanoma exacerbatesHEP mRNA:increased expression:zone of skin (human)RGD 
NAIPHumanskin melanoma exacerbatesHEP mRNA:increased expression:zone of skin (human)RGD 
BIRC2HumanTesticular Germ Cell Tumor exacerbatesHEP mRNA:increased expression:testis (human)RGD 
BIRC3HumanTesticular Germ Cell Tumor exacerbatesHEP mRNA:increased expression:testis (human)RGD 
BIRC5HumanTesticular Germ Cell Tumor exacerbatesHEP mRNA:increased expression:testis (human)RGD 
BIRC6HumanTesticular Germ Cell Tumor disease_progressionHEP mRNA:decreased expression:testis (human)RGD 
NAIPHumanTesticular Germ Cell Tumor exacerbatesHEP mRNA:increased expression:testis (human)RGD 
BIRC2Humanthymoma amelioratesHEP mRNA:increased expression:thymus (human)RGD 
BIRC5Humanthymoma amelioratesHEP mRNA:increased expression:thymus (human)RGD 
NAIPHumanthymoma amelioratesHEP mRNA:increased expression:thymus (human)RGD 
BIRC3Humanthyroid gland carcinoma disease_progressionHEP mRNA:increased expression:thyroid gland (human)RGD 
BIRC5Humanthyroid gland carcinoma exacerbatesHEP mRNA:increased expression:thyroid gland (human)RGD 
BIRC7Humanthyroid gland carcinoma disease_progressionHEP mRNA:increased expression:thyroid gland (human)RGD 
BIRC7Humanuveal melanoma exacerbatesHEP mRNA:increased expression:uvea (human)RGD 

Objects Annotated

Genes (Homo sapiens)
BIRC2  (baculoviral IAP repeat containing 2)
BIRC3  (baculoviral IAP repeat containing 3)
BIRC5  (baculoviral IAP repeat containing 5)
BIRC6  (baculoviral IAP repeat containing 6)
BIRC7  (baculoviral IAP repeat containing 7)
NAIP  (NLR family apoptosis inhibitory protein)
XIAP  (X-linked inhibitor of apoptosis)


Additional Information