5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer

Hu, Jiao; Othmane, Belaydi; Yu, Anze; Li, Huihuang; Cai, Zhiyong; Xu, Chao; Ren, Wen; Chen, Jinbo; Zu, Xiongbing

doi:10.1186/s12916-021-02163-6

Cited by 57 publications

(59 citation statements)

References 72 publications

(74 reference statements)

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“…In our research, we found that most m7G regulators were favorable factors for KIRC, whereas NUDT11, NUDT10, NSUN2, WDR4, METTL1, LSM1, and EIF4A1 were risk factors. These genes all play an oncogenic role in cancer ( Chen Z et al, 2021 ; Grisanzio et al, 2012 ; Hu J et al, 2021 ; Little et al, 2016 ; Wang et al, 2021 ; Xia et al, 2021 ; Ying et al, 2021 ; Zhao et al, 2021 ). Pan-cancer analysis showed that WDR4 and METTL1 were closely related to cancer immune infiltration and were immunotherapy targets in patients, and the high expression of KIRC was associated with poor prognosis of patients ( Gao et al, 2022 ; Zeng et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…METTL1 and WDR4 are highly expressed in a variety of tumors, such as liver cancer ( Chen D et al, 2021 ), intrahepatic cholangiocarcinoma ( Dai S et al, 2021 ), and lung cancer ( Ma et al, 2021 ), which is related to poor prognosis of patients. High expression of NSUN2 is associated with poor prognosis of gastric cancer ( Hu J et al, 2021 ) and esophageal squamous cell carcinoma ( Su et al, 2021 ). NUDT10 is a reliable prognostic marker of gastric cancer ( Chen Z et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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m7G regulator-mediated molecular subtypes and tumor microenvironment in kidney renal clear cell carcinoma

Chen

Nie²,

Gao³

et al. 2022

Front. Pharmacol.

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Background: RNA methylation modification plays an important role in immune regulation. m7G RNA methylation is an emerging research hotspot in the RNA methylation field. However, its role in the tumor immune microenvironment of kidney renal clear cell carcinoma (KIRC) is still unclear.Methods: We analyzed the expression profiles of 29 m7G regulators in KIRC, integrated multiple datasets to identify a novel m7G regulator-mediated molecular subtype, and developed the m7G score. We evaluated the immune tumor microenvironments in m7G clusters and analyzed the correlation of the m7G score with immune cells and drug sensitivity. We tested the predictive power of the m7G score for prognosis of patients with KIRC and verified the predictive accuracy of the m7G score by using the GSE40912 and E-MTAB-1980 datasets. The genes used to develop the m7G score were verified by qRT-PCR. Finally, we experimentally analyzed the effects of WDR4 knockdown on KIRC proliferation, migration, invasion, and drug sensitivity.Results: We identified three m7G clusters. The expression of m7G regulators was higher in cluster C than in other clusters. m7G cluster C was related to immune activation, low tumor purity, good prognosis, and low m7G score. Cluster B was related to drug metabolism, high tumor purity, poor survival, and high m7G score. Cluster A was related to purine metabolism. The m7G score can well-predict the prognosis of patients with KIRC, and its prediction accuracy based on the m7G score nomogram was very high. Patients with high m7G scores were more sensitive to rapamycin, gefitinib, sunitinib, and vinblastine than other patients. Knocking down WDR4 can inhibit the proliferation, migration, and invasion of 786-0 and Caki-1 cells and increase sensitivity to sorafenib and sunitinib.Conclusion: We proposed a novel molecular subtype related to m7G modification and revealed the immune cell infiltration characteristics of different subtypes. The developed m7G score can well-predict the prognosis of patients with KIRC, and our research provides a basis for personalized treatment of patients with KIRC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

m7G regulator-mediated molecular subtypes and tumor microenvironment in kidney renal clear cell carcinoma

Chen

Nie²,

Gao³

et al. 2022

Front. Pharmacol.

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“…This is consistent to previous studies showing that the patterns of m 6 A regulators are associated with immune evasion and prognosis in other cancer types. Zu’s group evaluated the expression landscape of regulators for 5-methylcytosine (5mC), an epigenetic modification [ 9 ]. They identified two clusters of 5mC regulators that were correlated with the classical molecular subtypes and prognosis of bladder cancer.…”

Section: Targeted Therapy: An Evolving Paradigmmentioning

confidence: 99%

Targeted therapies for cancer

Zhou

2022

BMC Med

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Targeted therapy is the key for improving overall survival while decreasing the undesirable adverse effects of cancer treatment. Patients who received matched targeted therapies showed dramatically improved overall survival (OS) and progression-free survival (PFS) compared to those without matched therapies. However, each patient responds to targeted therapy differently due to their unique genomic profile. The discrepancy of treatment response between clinical trials and real-world clinical practice highlights an unmet need to develop tailored therapies for individual patients. The development of cutting-edge technologies, such as next-generation sequencing, has enabled us to identify more actionable targets. In this special issue of BMC Medicine, a collection of highly translational and clinical oncology papers presented a series of studies on targeted therapies for a variety of cancer types, aiming to bridge the gap between genomic testing and precision medicine and spark innovations on improving the efficacy of targeted therapies.

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“…In addition, Gao et al ( Gao et al, 2019 ) found that high expression of NSUN2 could promote the proliferation and tumorigenesis of gallbladder carcinoma cells both in vitro and in vivo by closely cooperating with ribosomal protein L6. Recently, the role of m5C modification in cancers, including lung cancer, colon carcinoma, bladder cancer, and thyroid carcinoma, has been explored ( Pan et al, 2021a ; Pan et al, 2021b ; Chen et al, 2021 ; Gao et al, 2021 ; Geng et al, 2021 ; Gu et al, 2021 ; Hu et al, 2021 ; Li et al, 2021 ; Liu et al, 2021 ; Xu et al, 2021 ). In addition, He et al ( He et al, 2020a ) built a gene signature including 2 m5C regulators and found that it could effectively predict the prognosis of HCC.…”

Section: Introductionmentioning

confidence: 99%

Identification of the Expression Patterns and Potential Prognostic Role of 5-Methylcytosine Regulators in Hepatocellular Carcinoma

Liu

Zheng

Wang

et al. 2022

Front. Cell Dev. Biol.

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Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis. 5-methylcytosine (m5C) modification plays a nonnegligible role in tumor pathogenesis and progression. However, little is known about the role of m5C regulators in HCC.Methods: Based on 9 m5C regulators, the m5C modification patterns of HCC samples extracted from public databases were systematically evaluated and correlated with tumor immune and prognosis characteristics. An integrated model called the “m5Cscore” was constructed using principal component analysis, and its prognostic value was evaluated.Results: Almost all m5C regulators were differentially expressed between HCC and normal tissues. Through unsupervised clustering, three different m5Cclusters were ultimately uncovered; these clusters were characterized by differences in prognosis, immune cell infiltration, and pathway signatures. The m5Cscore was constructed to quantify the m5C modifications of individual patients. Subsequent analysis revealed that the m5Cscore was an independent prognostic factor of HCC and could be a novel indicator to predict the prognosis of HCC.Conclusion: This study comprehensively explored and systematically profiled the features of m5C modification in HCC. m5C modification patterns play a crucial role in the tumor immune microenvironment (TIME) and prognosis of HCC. The m5Cscore provides a more holistic understanding of m5C modification in HCC and provides a practical tool for predicting the prognosis of HCC. This study will help clinicians identify effective indicators of HCC to improve the poor prognosis of this disease.

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5mC regulator-mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide precision medicine in bladder cancer

Cited by 57 publications

References 72 publications

m7G regulator-mediated molecular subtypes and tumor microenvironment in kidney renal clear cell carcinoma

m7G regulator-mediated molecular subtypes and tumor microenvironment in kidney renal clear cell carcinoma

Targeted therapies for cancer

Identification of the Expression Patterns and Potential Prognostic Role of 5-Methylcytosine Regulators in Hepatocellular Carcinoma

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