Background: Increasing evidence shows cancer/testis antigens (CTAs) play a key role in oncogenesis. Our pre-study finds that MAGEA1 , MAGEA10 , MAGEB2 , KK-LC-1 , and CTAG1A/B  have high expression frequencies at the protein level. We aim to explore their prognostic role and correlations with clinical characteristics in resected lung cancer at the mRNA level.
Methods: Thirty-eight surgical lung cancer samples were included. Validation study was performed based on The Cancer Genome Atlas database. The prognostic roles of CTAs were evaluated by Kaplan–Meier and multivariate analysis.
Results: High expression of MAGEA1  (16.7% vs 65.0%, P =0.004), MAGEA10  (61.1% vs 95.0%, P =0.016), MAGEB2  (55.6% vs 95.0%, P =0.007), and KK-LC-1  (16.7% vs 55.0%, P =0.020) was closely correlated with lymph node metastasis at diagnosis. Patients with TNM stage II or III had a higher expression of MAGEA10 (57.1% vs 91.7%, P =0.034) and KK-LC-1  (14.3% vs 50.0%, P =0.039) compared with patients in TNM stage I. High CTAG1A/B  expression showed unfavorable prognosis in all cases (P <0.05). Subgroup analysis showed high CTAG1A/B  expression was a negative prognostic factor of survival (P =0.031) in patients with TNM stage II or III. Although no statistical significance was reached, high CTAG1A/B  also showed a similar prognostic trend in lung adenocarcinoma (ADC) and squamous cell carcinoma. The Cancer Genome Atlas database showed the negative prognostic role of CTAG1A/B  was mainly induced by CTAG1B  (NY-ESO-1, P =0.047) and high CTAG1B  expression (hazard ratio =2.733, 95% CI: 1.348–5.541, P =0.005) was an independent negative prognostic factor of lung ADC.
Conclusion: CTAs represent potential candidate targets for immunotherapy and their expression was closely correlated with tumor stage. High CTAG1B  expression was an independent negative prognostic factor of lung ADC.
Keywords: lung cancer, cancer/testis antigens, immunotherapy, prognosis