TTYH3, a potential prognosis biomarker associated with immune infiltration and immunotherapy response in lung cancer

Purpose The recognition of new diagnostic and prognostic biological markers for lung cancer is an essential and eager study. It’s shown that ion channels play important roles in regulating various cellular processes and have been suggested to be associated with patient survival. However, TTYH3, as a novel maxi-Cl− channel, its role in lung cancer remains elusive. Methods The expression, diagnosis and prognostic efficacy of TTYH3 were analyzed by public databases and clinical samples. Cell functional experiments used to explore the effects of TTYH3 on cell ability. GO and KEGG enrichment analysis revealed pathway that TTYH3 and its co-expressed genes were enriched in. TIMER and R language analyses were used to detect the correlation between TTYH3 and immune cell infiltration and the immunotherapy response. Results TTYH3 was found up-regulated in lung cancer tissues compared to normal tissues and possessed a prominent diagnostic and prognostic value. Knockdown TTYH3 significantly inhibited the proliferation of lung cancer cells. Enrichment analyses results showed that TTYH3 and its co-expressed genes were mainly involved in immune related signaling pathways. Further investigation clarified that TTYH3 had a positive correlation with the infiltration of macrophage, T cell regulatory, CD4+ T cell and high TTYH3 expression indicated worse immunotherapy response and shorter survival after immune checkpoint blockade treatment. Conclusion This study not only deciphers the diagnostic and prognostic value of TTYH3 but also provides TTYH3-based estimation of immunotherapy response for lung cancer patients, which might provide new strategies like anti-TTYH3 combined with immune therapy for the treatment of lung cancer.