Showkat A Malik1, Mosin S Khan1, Majeed Dar2, Mahboob Ul Hussain3, Syed Mudassar1. 1. Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir 190011, India. 2. Department of Cardiovascular and Thoracic Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir 190011, India. 3. Department of Biotechnology, University of Kashmir, Srinagar, Kashmir 190006, India.
Abstract
BACKGROUND: Hippo-LATS pathway is involved in regulating multiple phenotypes. TAZ (transcriptional co-activator with PDZ-binding motif) is a prominent proto-oncogene of this developmental pathway. Elevated TAZ expression has been observed in many cancers including Non-Small Cell lung cancer (NSCLC). OBJECTIVE: We elucidated the frequency of protein expression of TAZ gene in NSCLC patients of our population along with its relationship with clinicopathological parameters and determined its prognostic significance concerning survival in patients with resected tumor. METHODS: We looked into the protein expression of TAZ gene in sixty nine (n= 69) cases of NSCLC tissue and their corresponding normal lung tissue samples by western blotting. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of TAZ protein expressionon survival. RESULTS: Here, we found that TAZ protein expression was elevated in 49.27% (34 of 69) of NSCLC tissues as compared to only 13.04% (09 of 69) in normal lung tissues. TAZ protein expression was significantly associated with smoking, positive lymph node status and vascular invasion (P< 0.05). TAZ protein overexpression increased the hazards ratio by 2.6 (P= 0.005) on univariate analysis. Multivariable analysis confirmed that TAZ protein overexpression along with age and lymph node metastasis increased the hazard of death after adjusting for other clinicopathological factors (P< 0.05). Importantly, TAZ protein overexpression was associated with short overall survival and disease-free survival when compared with normal TAZ expression. CONCLUSION: These results indicate that TAZ is an independent prognostic factor and plays an important role in NSCLC progression and may serve as a novel therapeutic target of NSCLC.
BACKGROUND: Hippo-LATS pathway is involved in regulating multiple phenotypes. TAZ (transcriptional co-activator with PDZ-binding motif) is a prominent proto-oncogene of this developmental pathway. Elevated TAZ expression has been observed in many cancers including Non-Small Cell lung cancer (NSCLC). OBJECTIVE: We elucidated the frequency of protein expression of TAZ gene in NSCLCpatients of our population along with its relationship with clinicopathological parameters and determined its prognostic significance concerning survival in patients with resected tumor. METHODS: We looked into the protein expression of TAZ gene in sixty nine (n= 69) cases of NSCLC tissue and their corresponding normal lung tissue samples by western blotting. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of TAZ protein expressionon survival. RESULTS: Here, we found that TAZ protein expression was elevated in 49.27% (34 of 69) of NSCLC tissues as compared to only 13.04% (09 of 69) in normal lung tissues. TAZ protein expression was significantly associated with smoking, positive lymph node status and vascular invasion (P< 0.05). TAZ protein overexpression increased the hazards ratio by 2.6 (P= 0.005) on univariate analysis. Multivariable analysis confirmed that TAZ protein overexpression along with age and lymph node metastasis increased the hazard of death after adjusting for other clinicopathological factors (P< 0.05). Importantly, TAZ protein overexpression was associated with short overall survival and disease-free survival when compared with normal TAZ expression. CONCLUSION: These results indicate that TAZ is an independent prognostic factor and plays an important role in NSCLC progression and may serve as a novel therapeutic target of NSCLC.
Entities:
Keywords:
Lung cancer; NSCLC; TAZ; hazard ratio; protein expression; survival