Background: Cancer/testis antigen (CTA) expression was found to be highly heterogeneous in previous studies. We aimed to establish a precision CTA profiling in resected stage III non-small cell lung cancer (NSCLC) and demonstrate the best CTA combination covering the widest range of NSCLC cases.
Materials and methods: The expression of 10 CTAs was evaluated in 200 resected stage III NSCLC tissue specimens at protein level. Hierarchical clustering and python programming language analyses was used to demonstrate CTA expression and coverage.
Results: The most commonly expressed CTAs for total cases were MAGEA1 (60.0%), MAGEA10 (50.0%), and KK-LC-1 (47.5%). CTA expression was histology dependent, and concurrent expression was common. The best 2, 3, and 4 CTA combination covered 72.0%, 76.5%, and 79.5% of total cases, respectively. Stratified analysis based on variable clinicopathological characteristics achieved the maximum coverage of 92.3% with only 2 CTA combination in patients with features of male sex, positive smoking history, and adenocarcinoma, compared with a 85.0% coverage when 10 CTAs were assessed. Selected CTA expression was correlated with prognosis based on subgroup analysis. No significant difference was found between CTA expression and epidermal growth factor receptor mutant status.
Conclusion: We established an individualized CTA profiling in resected stage III NSCLC based on 10 CTA expression. With the help of computer programming language, the goal of the maximum CTA expression coverage was reached by using the least CTA combination based on sex, smoking history, and histology. These results were significant for the further study of CTA-specific T-cell immunotherapy.
Keywords: cancer/testis antigens; immunotherapy; lung cancer; profiling; prognosis.