Increased expression of ALDH1A1 protein is associated with poor prognosis in clear cell renal cell carcinoma

Med Oncol. 2013;30(2):574. doi: 10.1007/s12032-013-0574-z. Epub 2013 Apr 13.

Abstract

Aldehyde dehydrogenase 1A1 (ALDH1A1) has been characterized as a cancer stem cell marker in different types of tumors. It plays a key role in various biological processes in tumor, including cell proliferation, invasion and chemoresistance. Recently, ALDH1A1 has been described as a prognostic marker in various tumors. In this study, we detected the expression of ALDH1A1 in 95 clear cell renal cell carcinoma (ccRCC) by immunohistochemistry and correlated it with clinicopathological parameters and prognosis. We further explored the correlation of ALDH1A1 expression to proliferation, invasion and drug sensitivity of renal cancer cell in vitro by silencing of ALDH1A1 in A498 renal cell line. ALDH1A1 protein showed high expression in 53 of 95 cases of ccRCC (56.8 %), which was significantly higher than that in normal tissues (5/23, 21.7 %). ALDH1A1 overexpression was significantly associated with tumor stage (P = 0.000), recurrence (P = 0.000), tumor size (P = 0.000) and vascular invasion (P = 0.023). The Kaplan-Meier survival analysis demonstrated that ALDH1A1 overexpression was significantly associated with shorter recurrence-free survival and overall survival (P = 0.003 and P = 0.008, respectively). Multivariate analysis demonstrated that ALDH1A1 was an independent prognostic factor for patients with ccRCC. Experiments in vitro further showed ALDH1A1 played an essential role in proliferation, invasion and drug sensitivity of renal cancer cell. In conclusion, ALDH1A1 might be a potential molecular marker in ccRCC, which provided us with a new therapeutic target in ccRCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aldehyde Dehydrogenase / antagonists & inhibitors
  • Aldehyde Dehydrogenase / biosynthesis*
  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase / metabolism
  • Aldehyde Dehydrogenase 1 Family
  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor
  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / enzymology*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Drug Resistance, Neoplasm
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / enzymology*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Retinal Dehydrogenase
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Aldehyde Dehydrogenase 1 Family
  • Aldehyde Dehydrogenase
  • ALDH1A1 protein, human
  • Retinal Dehydrogenase
  • Cisplatin