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
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
adrenocortical carcinoma exacerbatesHEP 153344516; 153344516; 153344516mRNA:increased expression:adrenal gland (human)RGD 
adrenocortical carcinoma amelioratesHEP 153344516; 153344516; 153344516mRNA:increased expression:adrenal gland (human)RGD 
bladder urothelial carcinoma disease_progressionHEP 153344516; 153344516mRNA:increased expression:urinary bladder (human)RGD 
brain glioma exacerbatesHEP 153344516; 153344516; 153344516mRNA:increased expression:brain (human)RGD 
breast carcinoma amelioratesHEP 153344516mRNA:increased expression:breast (human)RGD 
breast carcinoma exacerbatesHEP 153344516; 153344516mRNA:increased expression:breast (human)RGD 
breast carcinoma disease_progressionHEP 153344516mRNA:increased expression:breast (human)RGD 
breast carcinoma disease_progressionHEP 153344516mRNA:decreased expression:breast (human)RGD 
cholangiocarcinoma amelioratesHEP 153344516mRNA:increased expression:bile duct (human)RGD 
chromophobe renal cell carcinoma exacerbatesHEP 153344516mRNA:increased expression:kidney (human)RGD 
clear cell renal cell carcinoma disease_progressionHEP 153344516mRNA:increased expression:kidney (human)RGD 
clear cell renal cell carcinoma exacerbatesHEP 153344516mRNA:increased expression:kidney (human)RGD 
clear cell renal cell carcinoma amelioratesHEP 153344516; 153344516mRNA:increased expression:kidney (human)RGD 
colon adenocarcinoma exacerbatesHEP 153344516mRNA:increased expression:colon (human)RGD 
esophageal carcinoma disease_progressionHEP 153344516mRNA:increased expression:esophagus (human)RGD 
gastric adenocarcinoma exacerbatesHEP 153344516; 153344516mRNA:increased expression:stomach (human)RGD 
gastric adenocarcinoma disease_progressionHEP 153344516; 153344516; 153344516mRNA:increased expression:stomach (human)RGD 
glioblastoma exacerbatesHEP 153344516mRNA:increased expression:brain (human)RGD 
head and neck squamous cell carcinoma exacerbatesHEP 153344516mRNA:increased expression:head or neck skin (human)RGD 
head and neck squamous cell carcinoma amelioratesHEP 153344516; 153344516mRNA:increased expression:head or neck skin (human)RGD 
hepatocellular carcinoma disease_progressionHEP 153344516mRNA:increased expression:liver (human)RGD 
hepatocellular carcinoma exacerbatesHEP 153344516mRNA:increased expression:liver (human)RGD 
lung adenocarcinoma amelioratesHEP 153344516; 153344516mRNA:increased expression:lung (human)RGD 
lung adenocarcinoma disease_progressionHEP 153344516mRNA:increased expression:lung (human)RGD 
lung squamous cell carcinoma disease_progressionHEP 153344516; 153344516mRNA:increased expression:lung (human)RGD 
Mesothelioma amelioratesHEP 153344516; 153344516mRNA:increased expression:mesothelium (human)RGD 
Mesothelioma exacerbatesHEP 153344516mRNA:increased expression:mesothelium (human)RGD 
ovarian serous cystadenocarcinoma exacerbatesHEP 153344516mRNA:increased expression:ovary (human)RGD 
pancreatic adenocarcinoma exacerbatesHEP 153344516; 153344516; 153344516mRNA:increased expression:pancreas (human)RGD 
pancreatic adenocarcinoma disease_progressionHEP 153344516mRNA:increased expression:pancreas (human)RGD 
papillary renal cell carcinoma exacerbatesHEP 153344516; 153344516mRNA:increased expression:kidney (human)RGD 
papillary renal cell carcinoma disease_progressionHEP 153344516mRNA:increased expression:kidney (human)RGD 
paraganglioma exacerbatesHEP 153344516; 153344516mRNA:increased expression:adrenal gland and chromaffin cell (human)RGD 
prostate adenocarcinoma amelioratesHEP 153344516mRNA:increased expression:prostate gland (human)RGD 
prostate adenocarcinoma exacerbatesHEP 153344516mRNALincreased expression:prostate gland (human)RGD 
rectum adenocarcinoma disease_progressionHEP 153344516mRNA:increased expression:rectum (human)RGD 
rectum adenocarcinoma amelioratesHEP 153344516mRNA:increased expression:rectum (human)RGD 
skin melanoma exacerbatesHEP 153344516; 153344516mRNA:increased expression:zone of skin (human)RGD 
Testicular Germ Cell Tumor exacerbatesHEP 153344516; 153344516; 153344516; 153344516mRNA:increased expression:testis (human)RGD 
Testicular Germ Cell Tumor disease_progressionHEP 153344516mRNA:decreased expression:testis (human)RGD 
thymoma amelioratesHEP 153344516; 153344516; 153344516mRNA:increased expression:thymus (human)RGD 
thyroid gland carcinoma disease_progressionHEP 153344516; 153344516mRNA:increased expression:thyroid gland (human)RGD 
thyroid gland carcinoma exacerbatesHEP 153344516mRNA:increased expression:thyroid gland (human)RGD 
uveal melanoma exacerbatesHEP 153344516mRNA: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