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Article: An intronic polymorphism in GRP78 improves chemotherapeutic prediction in non-small cell lung cancer

TitleAn intronic polymorphism in GRP78 improves chemotherapeutic prediction in non-small cell lung cancer
Authors
Issue Date2012
PublisherAmerican College of Chest Physicians. The Journal's web site is located at http://www.chestjournal.org
Citation
Chest, 2012, v. 141 n. 6, p. 1466-1472 How to Cite?
AbstractBackground: Glucose-regulated protein 78 (GRP78) is involved in not only the progression of non-small cell lung cancer (NSCLC) but also chemotherapeutic effects. We hypothesized that an intronic polymorphism (rs430397G>A) in GRP78 affects survival among patients with NSCLC treated with platinum-based chemotherapy. Methods: Blood samples of patients with advanced NSCLC (IIIB/IV) were maintained in our specimen bank between 2001 and 2006. Genomic DNA was genotyped for rs430397. Associations between rs430397 and platinum-based treatment response, overall survival (OS), NSCLC-related survival, progression-free survival (PFS), and relapses were evaluated. GRP78 RNA and protein in NSCLC tissues were tested by real-time polymerase chain reaction and immunohisto chemistry. Results: The AA genotype is significantly associated with platinum-based chemoresistance (P = .019) and NSCLC-related death(P = .022). OS, NSCLC-related survival, and PFS of the AA genotype group are decreased compared with the GG and AG genotype groups (log-rank P < .05, respectively). The AA group showed a higher prevalence of early NSCLC relapses than the AG and GG group(P = .030). In addition, the AA genotype showed a significantly increased risk for OS (hazard ratio, 1.95) and PFS (hazard ratio, 1.80) compared with the GG group. Functional analysis showed that NSCLC tissues with genotype AA have higher GRP78 RNA and protein expression compared with those carrying GG at rs430397. Conclusions: The rs430397 AA genotype of GRP78 is associated with reduced survival and higher prevalence of early relapses in patients with advanced NSCLC treated with platinum-based chemotherapy. © 2012 American College of Chest Physicians.
Persistent Identifierhttp://hdl.handle.net/10722/179278
ISSN
2015 Impact Factor: 5.94
2015 SCImago Journal Rankings: 3.176
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhu, Xen_US
dc.contributor.authorLin, MCMen_US
dc.contributor.authorFan, Wen_US
dc.contributor.authorTian, Len_US
dc.contributor.authorWang, Jen_US
dc.contributor.authorNg, SSen_US
dc.contributor.authorWang, Men_US
dc.contributor.authorKung, Hen_US
dc.contributor.authorLi, Den_US
dc.date.accessioned2012-12-19T09:53:38Z-
dc.date.available2012-12-19T09:53:38Z-
dc.date.issued2012en_US
dc.identifier.citationChest, 2012, v. 141 n. 6, p. 1466-1472en_US
dc.identifier.issn0012-3692en_US
dc.identifier.urihttp://hdl.handle.net/10722/179278-
dc.description.abstractBackground: Glucose-regulated protein 78 (GRP78) is involved in not only the progression of non-small cell lung cancer (NSCLC) but also chemotherapeutic effects. We hypothesized that an intronic polymorphism (rs430397G>A) in GRP78 affects survival among patients with NSCLC treated with platinum-based chemotherapy. Methods: Blood samples of patients with advanced NSCLC (IIIB/IV) were maintained in our specimen bank between 2001 and 2006. Genomic DNA was genotyped for rs430397. Associations between rs430397 and platinum-based treatment response, overall survival (OS), NSCLC-related survival, progression-free survival (PFS), and relapses were evaluated. GRP78 RNA and protein in NSCLC tissues were tested by real-time polymerase chain reaction and immunohisto chemistry. Results: The AA genotype is significantly associated with platinum-based chemoresistance (P = .019) and NSCLC-related death(P = .022). OS, NSCLC-related survival, and PFS of the AA genotype group are decreased compared with the GG and AG genotype groups (log-rank P < .05, respectively). The AA group showed a higher prevalence of early NSCLC relapses than the AG and GG group(P = .030). In addition, the AA genotype showed a significantly increased risk for OS (hazard ratio, 1.95) and PFS (hazard ratio, 1.80) compared with the GG group. Functional analysis showed that NSCLC tissues with genotype AA have higher GRP78 RNA and protein expression compared with those carrying GG at rs430397. Conclusions: The rs430397 AA genotype of GRP78 is associated with reduced survival and higher prevalence of early relapses in patients with advanced NSCLC treated with platinum-based chemotherapy. © 2012 American College of Chest Physicians.en_US
dc.languageengen_US
dc.publisherAmerican College of Chest Physicians. The Journal's web site is located at http://www.chestjournal.orgen_US
dc.relation.ispartofChesten_US
dc.titleAn intronic polymorphism in GRP78 improves chemotherapeutic prediction in non-small cell lung canceren_US
dc.typeArticleen_US
dc.identifier.emailLin, MCM: mcllin@hkucc.hku.hken_US
dc.identifier.emailNg, SS: ssmng@hku.hken_US
dc.identifier.authorityLin, MCM=rp00746en_US
dc.identifier.authorityNg, SS=rp00767en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1378/chest.11-0469en_US
dc.identifier.pmid21940774-
dc.identifier.scopuseid_2-s2.0-84862003614en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-84862003614&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume141en_US
dc.identifier.issue6en_US
dc.identifier.spage1466en_US
dc.identifier.epage1472en_US
dc.identifier.isiWOS:000305039300019-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridZhu, X=34869035800en_US
dc.identifier.scopusauthoridLin, MCM=7404816359en_US
dc.identifier.scopusauthoridFan, W=24070406000en_US
dc.identifier.scopusauthoridTian, L=55173110800en_US
dc.identifier.scopusauthoridWang, J=36172185600en_US
dc.identifier.scopusauthoridNg, SS=7403358718en_US
dc.identifier.scopusauthoridWang, M=54682493900en_US
dc.identifier.scopusauthoridKung, H=7402514190en_US
dc.identifier.scopusauthoridLi, D=24463373900en_US

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