0
Original Research: CANCER |

An Intronic Polymorphism in GRP78 Improves Chemotherapeutic Prediction in Non-small Cell Lung CancerGRP78 Polymorphism Predicts Chemotherapy

Xiao Zhu, PhD; Marie C. M. Lin, PhD; Wenguo Fan, MD; Linwei Tian, MD, MPH; Jinlong Wang, MSc; Samuel S. Ng, PhD; Min Wang, MD; Hsiangfu Kung, PhD; Dongpei Li, MD
Author and Funding Information

From the Guangdong Province Key Laboratory of Medical Molecular Diagnosis (Dr Zhu), Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Dongguan; Cancer Institute (Drs Zhu and Wang and Mr Wang), Affiliated Tumor Hospital, Guangzhou Medical University, Guangzhou; Department of Surgery (Dr Lin), Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong; Department of Oral Anatomy and Physiology (Dr Fan), Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou; Department of Epidemiology (Dr Tian), School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong; School of Biological Sciences (Dr Ng), The University of Hong Kong, Hong Kong; Li Ka Shing Institute of Medical Sciences (Dr Kung), The Chinese University of Hong Kong, Hong Kong; and Zhongshan School of Medicine (Drs Fan and Li), Sun Yat-sen University, Guangzhou, China.

Correspondence to: Dongpei Li, MD, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China; e-mail: lidp@mail.sysu.edu.cn


For editorial comment see page 1377

Funding/Support: This study was supported by National Natural Science Foundation of China [Grant 81071697], Natural Science Foundation of Guangdong Province [Grant 2011040003694], Research Project of Education Bureau of Guangzhou City [Grant 10A192], Research Project of Health Bureau of Guangzhou City [Grant 201102A 213005], and Research Project of Science and Information Technology of Guangzhou City [Grant 12C22061657].

Drs Zhu, Lin, and Fan contributed equally to this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


© 2012 American College of Chest Physicians


Chest. 2012;141(6):1466-1472. doi:10.1378/chest.11-0469
Text Size: A A A
Published online

Background:  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 immunohistochemistry.

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.

Figures in this Article

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

MEMBER & INDIVIDUAL SUBSCRIBER

Want Access?

NEW TO CHEST?

Become a CHEST member and receive a FREE subscription as a benefit of membership.

Individuals can purchase this article on ScienceDirect.

Individuals can purchase a subscription to the journal.

Individuals can purchase a subscription to the journal or buy individual articles.

Learn more about membership or Purchase a Full Subscription.

INSTITUTIONAL ACCESS

Institutional access is now available through ScienceDirect and can be purchased at myelsevier.com.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543