title: Validation of cofilin-1 as a biomarker in non-small cell lung cancer: application of quantitative method in a retrospective cohort.
abstract: OBJECTIVE
  Cofilin is a cytoskeletal protein whose overexpression has been associated with aggressiveness in several types of malignancies. Here, we established and optimized a simple semi-quantitative immunohistochemistry (SQ-IHC) method for cofilin quantification in tumor biopsies, and applied it in a retrospective cohort of NSCLC patients aiming at validating the use of cofilin-1 as a prognostic biomarker.
  
  
  METHODS
  The SQ-IHC method for cofilin-1 quantification was established and applied in a NSCLC cohort. An archival collection of biopsies from 50 patients with clinicopathological information and 5 years follow-up was accessed. Association between cofilin-1 immunocontent and clinical outcome was assessed using standard Kaplan-Meier mortality curves and the log-rank test. To evaluate the robustness of our findings, three different partitional clustering strategies were used to stratify patients into two groups according to the biomarker expression level (hierarchical clustering, Kmeans and median cutoff).
  
  
  RESULTS
  In all the three different partitional clustering we used, survival analysis showed that patient with high cofilin-1 immunocontent had a lower overall survival rate (P < 0.05), and could be used to discriminate between good and bad prognosis. No other correlation was found when the variables age, sex or histological type were tested in association with patients outcome or with cofilin immunocontent.
  
  
  CONCLUSIONS
  Our method showed good sensitivity/specificity to indicate the outcome of patients according to their cofilin immunocontent in biological samples. Its application in a retrospective cohort and the results presented here are an important step toward the validation process of cofilin-1 as a prognostic biomarker.
authors: Department of Biochemistry, ICBS/Federal University of Rio Grande do Sul (UFRGS), 2600 Ramiro Barcelos St., Porto Alegre, 90035-003, Brazil.
authors: Carolina B
authors: CB
authors: Müller
authors: Rafael L S
authors: RL
authors: de Barros
authors: Mauro A A
authors: MA
authors: Castro
authors: Fernanda M
authors: FM
authors: Lopes
authors: Rosalva T
authors: RT
authors: Meurer
authors: Adriana
authors: A
authors: Roehe
authors: Guilherme
authors: G
authors: Mazzini
authors: Jane Maria
authors: JM
authors: Ulbrich-Kulczynski
authors: Felipe
authors: F
authors: Dal-Pizzol
authors: Marilda C
authors: MC
authors: Fernandes
authors: José C F
authors: JC
authors: Moreira
authors: Léder L
authors: LL
authors: Xavier
authors: Fábio
authors: F
authors: Klamt
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D051338:Cofilin 1 / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D015331:Cohort Studies; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C495810:CFL1 protein, human; D051338:Cofilin 1