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, tweety family member 3 (TTYH3), as a maxi-Cl- channel, its role in lung cancer remains elusive. METHODS: The expression, diagnostic and prognostic efficacy of TTYH3 were analyzed by public databases and clinical samples. Cell functional experiments were used to explore the effects of TTYH3 on cell viability. GO and KEGG enrichment analysis revealed underlying pathways that TTYH3 and its co-expressed genes were enriched in. TIMER, TIDE and R language analyses were used to detect the correlation between TTYH3 and immune infiltration cell and immunotherapy response. RESULTS: TTYH3 was up-regulated in lung cancer tissues compared to normal tissues and possessed a prominent diagnostic and prognostic value. TTYH3 knockdown significantly inhibited the proliferation of lung cancer cells. Enrichment analyses 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 TAMs, Treg infiltration as well as T cell exhaustion and high TTYH3 expression indicated worse immunotherapy response and shorter survival after immune checkpoint blockade treatment. CONCLUSION: This study not only revealed the diagnostic and prognostic value of TTYH3 but also provided 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.