LGR5 and ALDH1A1 served as prognostic and predictive markers for non-small cell lung cancer

Abstract

Objective To investigate the value of leucine-rich repeat-containing G protein coupled receptor 5 (LGR5) and aldehyde dehydrogenase 1A1 (ALDH1A1) in progression and prognosis of non-small-cell lung cancer (NSCLC), in order to find new targets for NSCLC-targeted imaging and radiation therapy. Methods Fresh tissues (n=24) and paraffin embedding tissues (n=109) of patients with NSCLC were collected from the First Affiliated Hospital of Soochow University between November 2009 and March 2012. Quantitative real time-PCR was used for the investigation of expression of LGR5 and ALDH1A1 mRNA in 24 NSCLC patients. Immunohistochemistry (IHC) was used for detecting LGR5 and ALDH1A1 expressions in NSCLC tissues and adjacent normal tissues. Data were analyzed by Mann-Whitney u test, χ2 test, Pearson correlation analysis, Kaplan-Meier method, Cox proportional hazards regression model. Results Compared with adjacent normal tissues, LGR5 and ALDH1A1 mRNA were frequently increased in NSCLC tissues (u values: 150, 74, both P<0.01), and the expression of LGR5 and ALDH1A1 mRNA was significantly correlated (r=0.416, P<0.05). Positive LGR5 and ALDH1A1 expression was defined in 28.44%(31/109) and 41.28%(45/109) of the NSCLC tumors, respectively. Further analysis indicated that 24 of the LGR5 positive samples (77.42%, 24/31) expressed ALDH1A1 (r=0.388, P<0.01). LGR5 and ALDH1A1 expressions in NSCLC with higher TNM stage were significantly higher than those in NSCLC with lower TNM stage (χ2 values: 4.64, 5.24, both P<0.05). Coexpression of LGR5 and ALDH1A1 in NSCLC with lymph node metastasis was higher than that in NSCLC without lymph node metastasis (χ2=4.12, P<0.05). High expression of LGR5 or ALDH1A1 was related to poor prognosis (χ2 values: 6.24, 4.18, both P<0.05), and NSCLC patients with coexpression of LGR5 and ALDH1A1 had a poorer prognosis than the others (χ2=10.63, P<0.01). Both of them were independent risk factors of a poorer prognosis (corrected hazard ratio (95% CI): 2.361(1.106-5.037), 2.306(1.101-4.830); both P<0.05). Conclusions The expressions of LGR5 and ALDH1A1 are closely associated with the tumorigenesis, metastasis and poor prognosis of NSCLC. LGR5 and ALDH1A1 might be new targets for NSCLC-targeted tumor imaging and radiation therapy. Key words: Carcinoma, non-small-cell lung; Prognosis; Receptors; G-protein-coupled; Aldehyde dehydrogenase