A systematic review and meta-analysis: Association between MGMT hypermethylation and the clinicopathological characteristics of non-small-cell lung carcinoma

Chen, Lin; Wang, Yong; Liu, Fen; Xu, Liyao; Peng, Feifei; Zhao, Ning; Fu, Biqi; Zhu, Zijie; Shi, Yu; Liu, Jiansheng; Wu, Renrui; Wang, Chen; Yao, Shengmin; Li, Yong

doi:10.1038/s41598-018-19949-z

Cited by 13 publications

(15 citation statements)

References 45 publications

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“…appears also in other human cancers such as cervical cancer [167], lung cancer [168], and glioblastoma [169].…”

Section: Interplay Of Dna Repair Pathwaysmentioning

confidence: 97%

“…Meta-analysis of 10 studies comprising 910 ovarian tissue samples by Qiao et al concluded that the inactivation of MGMT might be associated with carcinogenesis in specific histological types of EOC [26]. Aberrant MGMT promoter methylation appears also in other human cancers such as cervical cancer [167], lung cancer [168], and glioblastoma [169].…”

Section: Direct Repairmentioning

confidence: 99%

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DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

Tomášová

Čumová

Šeborová

et al. 2020

Cancers

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There is ample evidence for the essential involvement of DNA repair and DNA damage response in the onset of solid malignancies, including ovarian cancer. Indeed, high-penetrance germline mutations in DNA repair genes are important players in familial cancers: BRCA1, BRCA2 mutations or mismatch repair, and polymerase deficiency in colorectal, breast, and ovarian cancers. Recently, some molecular hallmarks (e.g., TP53, KRAS, BRAF, RAD51C/D or PTEN mutations) of ovarian carcinomas were identified. The manuscript overviews the role of DNA repair machinery in ovarian cancer, its risk, prognosis, and therapy outcome. We have attempted to expose molecular hallmarks of ovarian cancer with a focus on DNA repair system and scrutinized genetic, epigenetic, functional, and protein alterations in individual DNA repair pathways (homologous recombination, non-homologous end-joining, DNA mismatch repair, base- and nucleotide-excision repair, and direct repair). We suggest that lack of knowledge particularly in non-homologous end joining repair pathway and the interplay between DNA repair pathways needs to be confronted. The most important genes of the DNA repair system are emphasized and their targeting in ovarian cancer will deserve further attention. The function of those genes, as well as the functional status of the entire DNA repair pathways, should be investigated in detail in the near future.

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“…appears also in other human cancers such as cervical cancer [167], lung cancer [168], and glioblastoma [169].…”

Section: Interplay Of Dna Repair Pathwaysmentioning

confidence: 97%

Section: Direct Repairmentioning

confidence: 99%

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

Tomášová

Čumová

Šeborová

et al. 2020

Cancers

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“…TMZ is an alkylating agent prodrug, and its effect on tumor cells is to methylate the O6 residues of guanine preventing DNA duplication during cell proliferation and inducing cell death and apoptosis [ 95 ]. However, the DNA repair enzyme O-6-methylguanine-DNA methyltransferase (MGMT) is able to reverse the effects of alkylating agents as TMZ [ 96 – 98 ]. The MGMT promoter methylation is directly related to patient’s prognosis, as low promoter methylation status induces a high MGMT expression and a shorter survival due to a remarkable chemoresistance.…”

Section: Introductionmentioning

confidence: 99%

A highlight on Sonic hedgehog pathway

et al. 2018

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Hedgehog (Hh) signaling pathway plays an essential role during vertebrate embryonic development and tumorigenesis. It is already known that Sonic hedgehog (Shh) pathway is important for the evolution of radio and chemo-resistance of several types of tumors. Most of the brain tumors are resistant to chemotherapeutic drugs, consequently, they have a poor prognosis. So, a better knowledge of the Shh pathway opens an opportunity for targeted therapies against brain tumors considering a multi-factorial molecular overview. Therefore, emerging studies are being conducted in order to find new inhibitors for Shh signaling pathway, which could be safely used in clinical trials. Shh can signal through a canonical and non-canonical way, and it also has important points of interaction with other pathways during brain tumorigenesis. So, a better knowledge of Shh signaling pathway opens an avenue of possibilities for the treatment of not only for brain tumors but also for other types of cancers. In this review, we will also highlight some clinical trials that use the Shh pathway as a target for treating brain cancer.

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“…MGMT may play a very important role in carcinogenesis and invasive risk. It has been shown that MGMT hypermethylation is associated with an increased risk of NSCLC [8]. MGMT promoter methylation is also associated with the occurrence and invasion of melanoma [9].…”

Section: Discussionmentioning

confidence: 99%

“…O 6 -methylguanine-DNA methyltransferase (MGMT) is a widely studied specific DNA damage reversal repair protein that protects chromosomes from mutation, carcinogenesis, and cytotoxic effects of alkylating agents [7]. In previous studies, MGMT status was shown to be related to the occurrence and invasion of non-small cell lung cancer (NSCLC) [8], melanoma [9], malignant glioma [10], esophageal cancer [11], and prostate cancer [12]. MGMT also affected the chemotherapeutic effect of different tumor patients, but the results are controversial [8,9,13].…”

Section: Introductionmentioning

confidence: 99%

Association between MGMT status and response to alkylating agents in patients with neuroendocrine neoplasms: a systematic review and meta-analysis

Tan

2020

Bioscience Reports

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Background: O6-methylguanine-DNA methyltransferase (MGMT) is a specific DNA damage reversal repair protein. The influence of MGMT status on alkylating agent sensitivity in patients with neuroendocrine neoplasms (NENs) is controversial. We conducted a meta-analysis to assess the influence of MGMT status on the therapeutic sensitivity of alkylating agents in patients with NENs. Methods: We searched PubMed, EmBase, and Cochrane library public databases through 3 July 2019. The objective response rate (ORR) was the outcome data of interest. Subgroup analysis was performed according based on MGMT methylation and expression of MGMT protein. Results: Eleven studies were included in the meta-analysis. The proportion of patients with NENs that achieved an ORR after alkylating agent treatment was higher in the MGMT-deficient group than the non-deficient group (OR: 5.00; 95% CI: 3.04–8.22; P < 0.001; I2: 3%). Similar results were noted in the MGMT methylation and MGMT protein expression subgroups. Conclusion: Patients with NENs and MGMT methylation or low protein expression had a higher ORR proportion than patients without MGMT methylation or high protein expression. The MGMT status can be used as a biological indicator of the response to alkylating agent treatment in patients with NENs.

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A systematic review and meta-analysis: Association between MGMT hypermethylation and the clinicopathological characteristics of non-small-cell lung carcinoma

Cited by 13 publications

References 45 publications

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

DNA Repair and Ovarian Carcinogenesis: Impact on Risk, Prognosis and Therapy Outcome

A highlight on Sonic hedgehog pathway

Association between MGMT status and response to alkylating agents in patients with neuroendocrine neoplasms: a systematic review and meta-analysis

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