Clinicopathologic and prognostic implications of HOXA gene and its associated long-noncoding RNAs expression in non-small cell carcinoma: A meta-analysis

Background: We conducted an investigation into the correlation between HOXA and associated long-noncoding RNAs, along with their clinicopathologic and prognostic features in non-small cell lung cancer (NSCLC). Methods: A comprehensive search across multiple electronic databases, including PubMed and the Web of Science, was conducted to identify relevant studies. The association between HOXA, clinicopathologic parameters, and prognosis was assessed using relative risk (RR) and hazard ratio (HR) with a 95% confidence interval (CI). Data compilation was performed using STATA 12.0 software. Results: A total of 11 trials involving 2058 patients with NSCLC were included in our study. Significant correlations were observed between HOXA-AS2 and TNM stage (III-IV) (RR=2.173, 95% CI: 1.386-5.437, P< 0.05) and HOTTIP and age (>= 60-year-old) (RR=2.628, 95% CI: 1.185-5.829, P< 0.05) and non-smoking (RR=0.387, 95% CI: 0.156-0.959, P< 0.05). The combined results indicated a significant association between HOXA5 and increased overall survival (HR = 0.69, 95% CI = 0.57-0.84, P < .001). Additionally, HOXA-AS2, HOXA11 and HOTTIP were identified as potential independent predictors for poorer OS (HOXA-AS2: HR =3.48, 95% CI = 1.95 to 6.21, P < 0.05; HOXA11: HR=1.39, 95%CI = 1.08 to 1.79, P < 0.05; HOTTIP: HR=2.44, 95%CI = 1.10 to 5.42, P < 0.05). The prognostic significance of HOXA1, HOXA3 and HOXA4 was uncertain (HOXA1: HR=1.40, 95% CI =0.28 to 7.06, P > 0.05; HOXA3: HR=1.20, 95% CI = 0.96 to 1.50, P > 0.05; HOXA4: HR=0.97, 95% CI = 0.77 to 1.23, P > 0.05). Conclusions: The HOXA gene family has some potential to emerge as a novel prognostic factor for NSCLC and is correlated with some clinicopathological parameters such as the TNM stage, age and smoking. However, further meticulously designed prospective studies are warranted to substantiate these findings.