The Pan-Cancer Landscape of Crosstalk Between TRP Family and Tumour Microenvironment Relevant to Prognosis and Immunotherapy Response

Wu, Gujie; He, Min; Yin, Xi; Wang, Wenmaio; Zhou, Jiabin; Ren, Kuan; Chen, Xinming; Xue, Qun

doi:10.3389/fimmu.2022.837665

Cited by 7 publications

(6 citation statements)

References 39 publications

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“…Cancer is a complex and multifaceted disease driven by dysregulation of various cellular pathways, including those involved in cell metabolism, cell death, inflammation, migration, invasion, and immune evasion [ 16 , 17 ]. The tumor microenvironment (TME) plays a critical role in tumor progression and metastasis, serving as a key mediator of these processes [ 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

CDK16 as a potential prognostic biomarker correlated with an immunosuppressive tumor microenvironment and benefits in enhancing the effectiveness of immunotherapy in human cancers

Qi,

Wu,

et al. 2024

Aging

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Background: Cyclin-Dependent Kinase 16 (CDK16) plays significant biological roles in various diseases. Nonetheless, its function in different cancer types and its relationship with the Tumor Immune Microenvironment (TIME) are still not well-understood. Methods: We analyzed the expression profile, genetic alterations, clinical features, and prognostic value of CDK16 in pan-cancer using data from The Cancer Genome Atlas, Genotype-Tissue Expression databases, and in vitro experiments. Additionally, the TIMER2 and ImmuCellAI databases were utilized to assess the correlation between CDK16 expression and immune cell infiltration levels. Finally, we examined the correlation between CDK16 and the response to immunotherapy using collected immunotherapy data. Results: CDK16 is notably overexpressed in pan-cancer and is a risk factor for poor prognosis in various cancers. Our findings reveal that CDK16 regulates not only cell cycle-related functions to promote cell proliferation but also the autoimmunity-related functions of the innate and adaptive immune systems, along with other immune-related signaling pathways. Moreover, CDK16 overexpression contributes to an immunosuppressive tumor microenvironment, extensively suppressing immune-related features such as the expression of immune-related genes and pathways, as well as the count of immune-infiltrating cells. Our analysis indicated that individuals with low CDK16 expression showed higher response rates to immune checkpoint inhibitors and longer overall survival compared to those with high CDK16 expression. Conclusions: This study establishes CDK16 as a potential biomarker for predicting poor prognosis in a wide range of cancers. Its role in shaping the immunosuppressive tumor microenvironment and influencing the efficacy of immunotherapy highlights the urgent need for developing targeted therapies against CDK16, offering new avenues for cancer treatment and management.

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Section: Discussionmentioning

confidence: 99%

CDK16 as a potential prognostic biomarker correlated with an immunosuppressive tumor microenvironment and benefits in enhancing the effectiveness of immunotherapy in human cancers

Qi,

Wu,

et al. 2024

Aging

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“…Tumor-associated macrophages are an important part of tumor immune microenvironment ( 19 ), which are usually divided into two types, one is M1 macrophages, which are involved in inflammation and can kill cancer cells, and the other is M2 macrophage, which can promote tumor progression. Many studies have shown that, on the one hand, the abundance of macrophages in tumors is negatively correlated with the prognosis and survival of patients, and on the other hand, it is positively correlated with tumor drug resistance ( 20 , 21 ).…”

Section: Discussionmentioning

confidence: 99%

M2 macrophage inhibits the antitumor effects of Lenvatinib on intrahepatic cholangiocarcinoma

Yang,

Han,

Cui

et al. 2023

Front. Immunol.

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Background and objectivesThe relationship between the tumor microenvironment and the network of key signaling pathways in cancer plays a key role in the occurrence and development of tumors. Tumor-associated macrophages (TAMs) are important inflammatory cells in the tumor microenvironment and play an important role in tumorigenesis and progression. Macrophages in malignant tumors, mainly the M2 subtype, promote tumor progression by producing cytokines and down-regulating anti-inflammatory immune responses. Several articles have investigated the effect of macrophages on the sensitivity of cancer chemotherapeutic agents, but few such articles have been reported in cholangiocarcinoma, so we investigated the effect of M2 macrophage on the sensitivity of cholangiocarcinoma cells to Lenvatinib compared to M1.MethodsTHP-1 monocytes were polarized to M0 macrophage by phorbol 12-myristate 13-acetate (PMA) and then induced to differentiate into M1 and M2 macrophages by LPS, IFN-γ and IL-4 and IL-13, respectively. Macrophages and cholangiocarcinoma cells were co-cultured prior to 24 hours of Lenvatinib administration, cancer cell apoptosis was detected by western-blot, FACS analysis of Annexin V and PI staining. Furthermore, we use xCELLigence RTCA SP Instrument (ACEA Bio-sciences) to monitor cell viability of Lenvatinib administration in co-culture of cholangiocarcinoma cells and macrophages. After tumorigenesis in immunodeficient mice, Lenvatinib was administered, and the effects of M2 on biological characteristics of cholangiocarcinoma cells were investigated by immuno-histochemistry.ResultsmRNA and protein expression of M1 and M2 markers confirmed the polarization of THP-1 derived macrophages, which provided a successful and efficient model of monocyte polarization to TAMs. Lenvatinib-induced apoptosis of cholangiocarcinoma cells was significantly reduced when co-cultured with M2 macrophage, whereas apoptosis of cholangiocarcinoma cells co-cultured with M1 macrophage was increased. In the CDX model, Lenvatinib-induced cancer cell apoptosis was markedly reduced, and proliferative cells increased in the presence of M2 macrophages. Angiogenesis related factors was significantly increased in cholangiocarcinoma cells co-cultured with M2.ConclusionCompared with M1, M2 macrophages can inhibit the anti-tumor effect of Lenvatinib on cholangiocarcinoma through immune regulation, which may be related to the tumor angiogenesis factor effect of M2 macrophage.

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“…TRPC1, TRPC5/6, TRPM4, TRPM7/8, TRPV1/2, TRPV4, and TRPV6 are strongly associated with progression and could be new therapeutic targets for breast invasive carcinoma ( Chen et al, 2015 ; Saldías et al, 2021 ). In addition, several studies have identified the TRP ion channel family genes as promising predictors of prognosis and immunotherapeutic efficacy in patients with cancer through pan-cancer analysis ( Pan et al, 2022 ; Wu et al, 2022 ). However, the role of the TRP ion channel family in LUAD remains elusive.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a TRP-related gene signature for overall survival prediction in lung adenocarcinoma

Wu²,

Wang³

et al. 2022

Front. Genet.

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The transient receptor potential (TRP) channel is a type of channel protein widely distributed in peripheral and central nervous systems. Genes encoding TRP can be regulated by natural aromatic substances and serve as a therapeutic target for many diseases. However, the role of TRP-related genes in lung adenocarcinoma (LUAD) remains unclear. In this study, we used data from TCGA to screen and identify 17 TRP-related genes that are differentially expressed between LUAD and normal lung tissues. Based on these differentially expressed genes (DEGs), we classified all patients with LUAD into two subtypes. Significant differences in prognosis, clinical features, and immune cell infiltration characteristics were observed between the two subtypes. Subsequently, a prognostic signature with 12 genes was established by applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, and all patients with LUAD were classified into low- and high-risk groups. Patients with LUAD in the low-risk group had a significantly longer survival time than those in the high-risk group (p < 0.001), which was confirmed by LUAD data from the GSE72094 and GSE68571 validation datasets. Combined with clinical characteristics, the risk score was found to be an independent predictor of overall survival (OS) in patients with LUAD. Additionally, patients with high TRP scores exhibited poorer clinical characteristics and immune status while showing a sensitive response to chemotherapeutic agents. In conclusion, the TRP score is a promising biomarker for determining the prognosis, molecular subtype, tumor microenvironment, and guiding personalized treatment in patients with LUAD.

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The Pan-Cancer Landscape of Crosstalk Between TRP Family and Tumour Microenvironment Relevant to Prognosis and Immunotherapy Response

Cited by 7 publications

References 39 publications

CDK16 as a potential prognostic biomarker correlated with an immunosuppressive tumor microenvironment and benefits in enhancing the effectiveness of immunotherapy in human cancers

CDK16 as a potential prognostic biomarker correlated with an immunosuppressive tumor microenvironment and benefits in enhancing the effectiveness of immunotherapy in human cancers

M2 macrophage inhibits the antitumor effects of Lenvatinib on intrahepatic cholangiocarcinoma

Development and validation of a TRP-related gene signature for overall survival prediction in lung adenocarcinoma

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