Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced Neuropathy
| Autor: | Thomas Choudary Putti, Jingshan Ho, Raghav Sundar, Boon Cher Goh, Bernadette Reyna Asuncion, Aishwarya Bandla, Richie Chuan Teck Soong, Einar Wilder-Smith, Brendan Pang, Zul Fazreen, Michal Marek Hoppe, Joline Si Jing Lim, Anand D. Jeyasekharan, Samuel Guan Wei Ow, Soo-Chin Lee, Nesaretnam Barr Kumarakulasinghe, Lay Mui Poh, David Shao Peng Tan, Stacey Tan |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
medicine.medical_treatment Cancer Treatment lcsh:Medicine Cell Cycle Proteins Toxicology Pathology and Laboratory Medicine Nervous System Biochemistry chemistry.chemical_compound 0302 clinical medicine Charcot-Marie-Tooth Disease Breast Tumors Medicine and Health Sciences Medicine Nerve Tissue lcsh:Science Multidisciplinary Pharmaceutics Area under the curve Intracellular Signaling Peptides and Proteins Peripheral Nervous System Diseases Middle Aged Paclitaxel Neurology Oncology 030220 oncology & carcinogenesis Anesthesia Biomarker (medicine) Immunohistochemistry Female Anatomy Research Article Clinical Oncology Adult medicine.medical_specialty Urology Breast Neoplasms Research and Analysis Methods 03 medical and health sciences Text mining Breast cancer Drug Therapy Breast Cancer Chemotherapy Humans Peripheral Neuropathy Immunohistochemistry Techniques Aged Receiver operating characteristic Toxicity business.industry lcsh:R Biology and Life Sciences Cancers and Neoplasms medicine.disease Antineoplastic Agents Phytogenic Neuropathy Histochemistry and Cytochemistry Techniques Biological Tissue chemistry Immunologic Techniques lcsh:Q Clinical Medicine business 030217 neurology & neurosurgery Biomarkers |
| Zdroj: | PLoS ONE, Vol 11, Iss 10, p e0164319 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Introduction Sensory peripheral neuropathy caused by paclitaxel is a common and dose limiting toxicity, for which there are currently no validated predictive biomarkers. We investigated the relationship between the Charcot-Marie-Tooth protein NDRG1 and paclitaxel-induced neuropathy. Methods/Materials Archived mammary tissue specimen blocks of breast cancer patients who received weekly paclitaxel in a single centre were retrieved and NDRG1 immunohistochemistry was performed on normal nerve tissue found within the sample. The mean nerve NDRG1 score was defined by an algorithm based on intensity of staining and percentage of stained nerve bundles. NDRG1 scores were correlated with paclitaxel induced neuropathy Results 111 patients were studied. 17 of 111 (15%) developed severe paclitaxel-induced neuropathy. The mean nerve NDRG1 expression score was 5.4 in patients with severe neuropathy versus 7.7 in those without severe neuropathy (p = 0.0019). A Receiver operating characteristic (ROC) curve analysis of the mean nerve NDRG1 score revealed an area under the curve of 0.74 (p = 0.0013) for the identification of severe neuropathy, with a score of 7 being most discriminative. 13/54 (24%) subjects with an NDRG1 score < = 7 developed severe neuropathy, compared to only 4/57 (7%) in those with a score >7 (p = 0.017). Conclusion Low NDRG1 expression in nerve tissue present within samples of surgical resection may identify subjects at risk for severe paclitaxel-induced neuropathy. Since nerve biopsies are not routinely feasible for patients undergoing chemotherapy for early breast cancer, this promising biomarker strategy is compatible with current clinical workflow. |
| Databáze: | OpenAIRE |
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