HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Molecular profiling of multiple human cancers defines an inflammatory cancer-associated molecular pattern and uncovers KPNA2 as a uniform poor prognostic cancer marker.

AbstractBACKGROUND:
Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated.
METHODS AND FINDINGS:
Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An "Inflammatory Gene Integrated Score" was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers.
CONCLUSION:
This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.
AuthorsSaleh M Rachidi, Tingting Qin, Shaoli Sun, W Jim Zheng, Zihai Li
JournalPloS one (PLoS One) Vol. 8 Issue 3 Pg. e57911 ( 2013) ISSN: 1932-6203 [Electronic] United States
PMID23536776 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • TNFAIP6 protein, human
  • alpha Karyopherins
  • karyopherin alpha 2
Topics
  • Adenocarcinoma (complications, genetics, immunology, mortality)
  • Biomarkers, Tumor (genetics)
  • Carcinoma, Squamous Cell (complications, genetics, immunology, mortality)
  • Cell Adhesion Molecules (genetics)
  • Cluster Analysis
  • Colonic Neoplasms (complications, genetics, immunology, mortality)
  • Data Mining
  • Databases, Genetic
  • Gene Expression
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms (complications, genetics, immunology, mortality)
  • Humans
  • Inflammation (complications, genetics, immunology)
  • Neoplasm Staging
  • Neoplasms (complications, genetics, immunology, mortality)
  • Prognosis
  • Squamous Cell Carcinoma of Head and Neck
  • Workflow
  • alpha Karyopherins (genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: