Ttyh3, a Potential Prognosis Biomarker Associated with Immune Infiltration and Immunotherapy Response in Lung Cancer

Abstract

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, 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 viability. GO and KEGG enrichment analysis revealed 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 cell infiltration and immunotherapy response.

Results: TTYH3 was found 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 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, regulatory T cell, T cell exhaustion and high TTYH3 expression indicated worse immunotherapy response and shorter survival after immune checkpoint blockade treatment.

Conclusion: This study not only deciphered 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.

Note:
Funding Information: This work was supported by the National Natural Science Foundation of China (Nos. 81770180) and Hubei Provincial Natural Science Fund for Creative Research Groups (2018CFA018).

Declaration of Interests: The authors declare that they have no competing interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethics Approval Statement: This study has been approved by the Ethics Committee of Medical School of Wuhan University (Wuhan, China).

Keywords: Lung Cancer, TTYH3, biomarker, Proliferation, immune infiltration, Immunotherapy response