title: Low Levels of NDRG1 in Nerve Tissue Are Predictive of Severe Paclitaxel-Induced Neuropathy.
abstract: BACKGROUND
  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
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.
authors.forename: Raghav
authors.initials: R
authors.lastname: Sundar
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.|Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Anand D
authors.initials: AD
authors.lastname: Jeyasekharan
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.|Department of Pathology, National University Health System, Singapore, Singapore.
authors.forename: Brendan
authors.initials: B
authors.lastname: Pang
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.|Department of Pathology, National University Health System, Singapore, Singapore.
authors.forename: Richie Chuan Teck
authors.initials: RC
authors.lastname: Soong
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.
authors.forename: Nesaretnam Barr
authors.initials: NB
authors.lastname: Kumarakulasinghe
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.
authors.forename: Samuel Guan Wei
authors.initials: SG
authors.lastname: Ow
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.
authors.forename: Jingshan
authors.initials: J
authors.lastname: Ho
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.
authors.forename: Joline Si Jing
authors.initials: JS
authors.lastname: Lim
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.
authors.forename: David Shao Peng
authors.initials: DS
authors.lastname: Tan
authors.affiliation: Singapore Institute for Neurotechnology (SINAPSE), National University of Singapore, Singapore, Singapore.|Department of Medicine, National University Health System, Singapore, Singapore.|Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Einar P V
authors.initials: EP
authors.lastname: Wilder-Smith
authors.affiliation: Singapore Institute for Neurotechnology (SINAPSE), National University of Singapore, Singapore, Singapore.|Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Bandla
authors.affiliation: Singapore Institute for Neurotechnology (SINAPSE), National University of Singapore, Singapore, Singapore.
authors.forename: Stacey Sze Hui
authors.initials: SS
authors.lastname: Tan
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Bernadette Reyna
authors.initials: BR
authors.lastname: Asuncion
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Zul
authors.initials: Z
authors.lastname: Fazreen
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Michal Marek
authors.initials: MM
authors.lastname: Hoppe
authors.affiliation: Department of Pathology, National University Health System, Singapore, Singapore.
authors.forename: Thomas Choudary
authors.initials: TC
authors.lastname: Putti
authors.affiliation: Department of Pharmacy, National University Cancer Institute Singapore, National University Health System, Singapore, Singapore.
authors.forename: Lay Mui
authors.initials: LM
authors.lastname: Poh
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.|Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Boon Cher
authors.initials: BC
authors.lastname: Goh
authors.affiliation: Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore.|Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
authors.forename: Soo-Chin
authors.initials: SC
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002607:Charcot-Marie-Tooth Disease / Q000378:metabolism; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009417:Nerve Tissue / Q000378:metabolism*; D017239:Paclitaxel / Q000009:adverse effects* / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000378:metabolism*; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017239:Paclitaxel; D000099259:N-myc Downstream-Regulated Gene 1 Protein