The expression of human endogenous retrovirus subfamily H long terminal repeat associating protein 2 in lung cancer tissue and it’s clinical significance

Objective To observe the expression of human endogenous retrovirus subfamily H long terminal repeat associating protein 2 (HHLA2) in human lung cancer tissue and its correlation with patients’ clinicopathological characteristics and prognosis. Methods The tissue microarray and immunohistochemistry were used to examine the HHLA2 expression in 94 cases of lung adenocarcinoma and 75 cases of lung squamous cell carcinoma and their adjacent normal tissues. Wilcoxon rank test was used to compare the HHLA2 expression in lung cancer and corresponding normal adjacent tissues. The chi-square test was used to analyze the relationship between the HHLA2 expression in lung cancer tissues and clinicopathological features of the patients. Kaplan-Meier survival analysis was performed to analyze the correlation between HHLA2 expression and patients’ overall survival, and the Cox model was used to analyze the correlation between different clinical parameters and prognosis. Results The HHLA2 expression in lung cancer tissues was significantly higher than that in normal adjacent tissues (Lung adenocarcinoma: U=296.5, P=0.001; Lung squamous cell carcinoma: U=22.5, P=0.001). The high expression rate of HHLA2 in patients with lymph node metastasis was significantly higher than that in patients without lymph node metastasis (Lung adenocarcinoma: P=0.002; Lung squamous cell carcinoma: P=0.046). The high expression rate of HHLA2 in lung adenocarcinoma patients aged 60 years or older was significantly higher than that in patients<60 years old (P=0.023). There was no significant correlation between HHLA2 expression and other clinicopathological features of lung cancer patients. Kaplan-Merier survival analysis showed that the overall survival (OS) of patients with HHLA2 high expression level was significantly shorter than that of HHLA2 low expression level [Lung adenocarcinoma: hazard ratio (HR)=1.875, 95% confidence interval (CI): 1.099-3.196, P=0.021; Lung squamous cell carcinoma: HR=5.568, 95%CI: 2.024-15.320, P=0.001]. Multi-factor Cox model analysis indicated that lymph node metastasis (HR=1.766, 95%CI: 1.018-3.064, P=0.043) and HHLA2 high expression (HR=1.827, 95%CI: 1.061-3.146, P=0.030) were independent prognostic factors of lung adenocarcinoma, while age≥60 (HR=3.344, 95%CI: 1.123-9.963, P=0.030) and HHLA2 high expression (HR=3.617, 95%CI: 1.340-9.761, P=0.011) were independent prognostic factors of lung squamous cell carcinoma. Conclusion HHLA2 is highly expressed in lung cancer tissues, suggesting that HHLA2 plays an important role in the initiation and development of lung cancer. It could be used as a valuable risk factor to predict the prognose of lung cancer patients, and the molecule mechanism of HHLA2 in lung cancer progression merits further investigation. Key words: Lung Cancer; Human endogenous retrovirus subfamily H long terminal repeat associating protein 2; Tissue microarray; Prognosis