BackgroundTransient Receptor Potential (TRP) channel is a kind of channel protein widely distributed in peripheral and central nervous system. They can be regulated by natural aromatic substances and serve as a therapeutic target for many diseases. However, the role and function of the TRP family genes in tumours remain unclear.MethodsGene alterations (mutation, copy number, methylation), expression, clinical features, and prognostic value of the TRP family genes were evaluated in pan-cancer using data from The Cancer Genome Atlas and Genotype-Tissue Expression databases. TRP score was calculated by the ssGSEA function of the R package “GSVA”. The association of TRP score and the tumour microenvironment (TME), especially the tumour immune microenvironment (TIME), along with immunotherapy response were explored in-depth.ResultsTRP family genes were involved in tumour progression and highly associated with poor prognosis in a variety of cancers. TRP score was positively associated with malignant pathways in pan-cancer, such as IL6–JAK–STAT3 signalling, interferon-gamma response, and inflammatory response. All pathways were closely associated with TIME. Elevated TRP score also correlated with multiple immune-related characteristics of the TIME in pan-cancer. Moreover, the TRP score was a predictive biomarker for immune checkpoint inhibitor (ICI) treatments in patients with tumours.ConclusionsTRP family genes play a key role in pan-cancer and are closely associated with TME. Patients with high TRP scores have excellent immune-activated TIME and immunotherapy sensitivity. Therefore, the TRP score could be a potential biomarker for patients with tumours treated with ICI.

Background: Pyrroloquinoline quinone (PQQ) has been reported to exhibit cardioprotective and antioxidant activities. Accordingly, this study was developed to explore the effects of PQQ treatment on myocardial hypertrophy and the underlying mechanism of action governing any observed beneficial effects.Methods: A transverse aortic constriction (TAC) model of myocardial hypertrophy was established in vivo using C57BL/6 mice, while neonatal murine cardiomyocytes were stimulated with phenylephrine (PE) as an in vitro validation model system.Results: Treatment of TAC model mice with PQQ significantly suppressed myocardial hypertrophy and fibrosis, in addition to inhibiting the ferroptotic death of hypertrophic myocardial cells in vivo. Subsequent in vitro analyses revealed that treatment with PQQ was sufficient to significantly alleviate PE-induced hypertrophic activity and to prevent ferroptotic induction in these primary murine cardiomyocytes. At the mechanistic level, PQQ was found to promote the upregulation of Yes-associated Protein (YAP), to suppress YAP phosphorylation, and to drive the nuclear translocation of YAP within hypertrophic cardiomyocytes. The use of a specific siRNA construct to knock down YAP expression in vitro further confirmed the ability of PQQ to protect against myocardial hypertrophy at least in part through anti-ferroptotic mechanisms.Conclusion: PQQ can regulate the pathogenesis of myocardial hypertrophy through the induction of YAP-related anti-ferroptotic activity, highlighting the potential value of PQQ as a novel therapeutic agent capable of slowing or preventing the progression of myocardial hypertrophy and thus delaying the onset of heart failure.