دورية أكاديمية
The unfolded protein response regulator GRP78 is a novel predictive biomarker in colorectal cancer.
| العنوان: | The unfolded protein response regulator GRP78 is a novel predictive biomarker in colorectal cancer. |
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| المؤلفون: | Thornton M; Department of Molecular and Clinical Cancer Medicine, University of Liverpool, L3 9TA, United Kingdom., Aslam MA, Tweedle EM, Ang C, Campbell F, Jackson R, Costello E, Rooney PS, Vlatković N, Boyd MT |
| المصدر: | International journal of cancer [Int J Cancer] 2013 Sep 15; Vol. 133 (6), pp. 1408-18. Date of Electronic Publication: 2013 Apr 08. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0042124 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-0215 (Electronic) Linking ISSN: 00207136 NLM ISO Abbreviation: Int J Cancer Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1995- : New York, NY : Wiley-Liss Original Publication: 1966-1984 : Genève : International Union Against Cancer |
| مواضيع طبية MeSH: | Unfolded Protein Response*, Colorectal Neoplasms/*drug therapy , Heat-Shock Proteins/*physiology, Adult ; Aged ; Apoptosis/drug effects ; Biomarkers, Tumor/analysis ; Colorectal Neoplasms/chemistry ; Colorectal Neoplasms/mortality ; Colorectal Neoplasms/pathology ; Endoplasmic Reticulum Chaperone BiP ; Female ; Fluorouracil/pharmacology ; Heat-Shock Proteins/analysis ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoplasm Staging ; Tumor Suppressor Protein p53/analysis |
| مستخلص: | Adjuvant fluoropyrimidine-based (5-FU) chemotherapy is a mainstay of treatment for colorectal cancer (CRC), but only provides benefit for a subset of patients. To improve stratification we examined (for the first time in CRC), whether analysis of GRP78 expression provides a predictive biomarker and performed functional studies to examine the role of GRP78 in sensitivity to 5-FU. 396 CRC patient samples were collected in a prospective uniform manner and GRP78 expression was determined by immunohistochemistry on tissue microarrays using a well-validated antibody. Expression was correlated with clinicopathological parameters and survival. The role of GRP78 in 5-FU sensitivity was examined in CRC cells using siRNA, drug inhibition and flow cytometry. GRP78 expression was significantly elevated in cancer tissue (p < 0.0001), and correlated with depth of invasion (p = 0.029) and stage (p = 0.032). Increased overall 5-year survival was associated with high GRP78 expression (p = 0.036). Patients with stage II cancers treated by surgery alone, with high GRP78 also had improved survival (71% v 50%; p = 0.032). Stage III patients with high GRP78 showed significant benefit from adjuvant chemotherapy (52% vs. 28%; p = 0.026), whereas patients with low GRP78 failed to benefit (28% vs. 32%; p = 0.805). Low GRP78 was an independent prognostic indicator of reduced overall 5-year survival (p = 0.004; HR = 1.551; 95%CI 1.155-2.082). In vitro, inhibition of GRP78 reduces apoptosis in response to 5-FU in p53 wild-type cells. GRP78 expression may provide a simple additional risk stratification to inform the adjuvant treatment of CRC and future studies should combine analysis with determination of p53 status. (Copyright © 2013 UICC.) |
| معلومات مُعتمدة: | United Kingdom Cancer Research UK |
| فهرسة مساهمة: | Keywords: GRP78; biological markers; colorectal neoplasms; retrospective studies; tumour suppressor protein p53; unfolded protein response |
| المشرفين على المادة: | 0 (Biomarkers, Tumor) 0 (Endoplasmic Reticulum Chaperone BiP) 0 (HSPA5 protein, human) 0 (Heat-Shock Proteins) 0 (TP53 protein, human) 0 (Tumor Suppressor Protein p53) U3P01618RT (Fluorouracil) |
| تواريخ الأحداث: | Date Created: 20130305 Date Completed: 20130912 Latest Revision: 20211203 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1002/ijc.28137 |
| PMID: | 23456958 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1097-0215 |
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| DOI: | 10.1002/ijc.28137 |