DNA Methylation and Hydroxymethylation in Cervical Cancer: Diagnosis, Prognosis and Treatment

Zhu, Hongming; Zhu, He; Tian, Miao; Wang, Dongying; He, Jiaxing; Xu, Tianmin

doi:10.3389/fgene.2020.00347

Cited by 50 publications

(34 citation statements)

References 88 publications

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“…Epigenetic modification of DNA refers to a chemical modification process in which a methyl group is transferred to a cytosine, most commonly at a CpG (cytosine linked to guanine by a phosphate group, cytosine-phospho-guanine, 5′-C-p-G-3′) site [ 11 ]. DNA methylation without base sequence alteration is considered as the most common and highly dynamic epigenetic modification, which is the result of the function of cytosine DNA methyltransferases (DNMTs) [ 12 , 13 ]. DNMTs contain three members: DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3a (DNMT3a), and DNA methyltransferase 3b (DNMT3b).…”

Section: Epigenetic Modification Expression Profile In Keloidmentioning

confidence: 99%

Epigenetic modification mechanisms involved in keloid: current status and prospect

Ren

Hou

et al. 2020

Clin Epigenet

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Keloid, a common dermal fibroproliferative disorder, is benign skin tumors characterized by the aggressive fibroblasts proliferation and excessive accumulation of extracellular matrix. However, common therapeutic approaches of keloid have limited effectiveness, emphasizing the momentousness of developing innovative mechanisms and therapeutic strategies. Epigenetics, representing the potential link of complex interactions between genetics and external risk factors, is currently under intense scrutiny. Accumulating evidence has demonstrated that multiple diverse and reversible epigenetic modifications, represented by DNA methylation, histone modification, and non-coding RNAs (ncRNAs), play a critical role in gene regulation and downstream fibroblastic function in keloid. Importantly, abnormal epigenetic modification manipulates multiple behaviors of keloid-derived fibroblasts, which served as the main cellular components in keloid skin tissue, including proliferation, migration, apoptosis, and differentiation. Here, we have reviewed and summarized the present available clinical and experimental studies to deeply investigate the expression profiles and clarify the mechanisms of epigenetic modification in the progression of keloid, mainly including DNA methylation, histone modification, and ncRNAs (miRNA, lncRNA, and circRNA). Besides, we also provide the challenges and future perspectives associated with epigenetics modification in keloid. Deciphering the complicated epigenetic modification in keloid is hopeful to bring novel insights into the pathogenesis etiology and diagnostic/therapeutic targets in keloid, laying a foundation for optimal keloid ending.

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Section: Epigenetic Modification Expression Profile In Keloidmentioning

confidence: 99%

Epigenetic modification mechanisms involved in keloid: current status and prospect

Ren

Hou

et al. 2020

Clin Epigenet

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show abstract

“…The low specificity (31%) and positive predictive value (37%) even make the situation worse because they lead to more patients undergoing unnecessary referrals 37 . Recent studies have shown the correlation between epigenetics and development and progression of cervical cancer 41 . Increased methylation of host genes has been observed in women with cervical precancer and cancer.…”

Section: Discussionmentioning

confidence: 99%

Artificial intelligence-assisted fast screening cervical high grade squamous intraepithelial lesion and squamous cell carcinoma diagnosis and treatment planning

Wang

Liou

Lin

et al. 2021

Sci Rep

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Every year cervical cancer affects more than 300,000 people, and on average one woman is diagnosed with cervical cancer every minute. Early diagnosis and classification of cervical lesions greatly boosts up the chance of successful treatments of patients, and automated diagnosis and classification of cervical lesions from Papanicolaou (Pap) smear images have become highly demanded. To the authors’ best knowledge, this is the first study of fully automated cervical lesions analysis on whole slide images (WSIs) of conventional Pap smear samples. The presented deep learning-based cervical lesions diagnosis system is demonstrated to be able to detect high grade squamous intraepithelial lesions (HSILs) or higher (squamous cell carcinoma; SQCC), which usually immediately indicate patients must be referred to colposcopy, but also to rapidly process WSIs in seconds for practical clinical usage. We evaluate this framework at scale on a dataset of 143 whole slide images, and the proposed method achieves a high precision 0.93, recall 0.90, F-measure 0.88, and Jaccard index 0.84, showing that the proposed system is capable of segmenting HSILs or higher (SQCC) with high precision and reaches sensitivity comparable to the referenced standard produced by pathologists. Based on Fisher’s Least Significant Difference (LSD) test (P < 0.0001), the proposed method performs significantly better than the two state-of-the-art benchmark methods (U-Net and SegNet) in precision, F-Measure, Jaccard index. For the run time analysis, the proposed method takes only 210 seconds to process a WSI and is 20 times faster than U-Net and 19 times faster than SegNet, respectively. In summary, the proposed method is demonstrated to be able to both detect HSILs or higher (SQCC), which indicate patients for further treatments, including colposcopy and surgery to remove the lesion, and rapidly processing WSIs in seconds for practical clinical usages.

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“…As a result, the mortality rates are still high [27]. Nowadays, an increasing number of studies have demonstrated the importance of a new type of regulation by epigenetics in speci c genes in the progression of cervical cancer [29]. This provides new ideas for the treatment of cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Therapeutic Targets and Prognostic Biomarkers of CXC Chemokines in Cervical Cancer Microenvironment

Kong

Zhao

Chen

et al. 2021

Preprint

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Background: It is well known that the tumor microenvironment (TME) has been received an increasing number of attention. CXC chemokines could regulate immune cell transport and tumor cell activity, thus exerting anti-tumor immunity. However, studies on the expression and prognosis of CXC chemokines in cervical cancer (CC) are more limited. Methods: The study investigated the role of CXC chemokines in the TME and prognosis of CC using public databases. Moreover, quantitative real-time PCR (Q-PCR) and immunohistochemistry (IHC) of CXC chemokines were performed to further verify. Results: The transcriptional levels of CXCL1/3/5/6/8/9/10/11/13/14/16/17 in CC tissues were significantly elevated while the transcriptional levels of CXCL2/4/7/12 were significantly reduced. We reached a consistent conclusion that the expression of CXCL9/10/11/13 was verified by Q-PCR and IHC. Moreover, CC patients with low transcriptional levels of CXCL1/2/3/4/5/8 were signifi-cantly associated with longer overall survival (OS). Our data suggest that RELA, NFKB1, and SP1 are key transcription factors for CXC chemokines, and the LCK, LYN and PAK are CXC chemokine kinases targets. We found significant correlations among the expression of CXC chemokines and the infiltration of six types of immune cells. Conclusions: We performed a comprehensive analysis of CXC chemokines via clinical data and some online tumor database. Our results may provide new idea for the selection of immunotherapeutic targets and prognostic biomarkers for cervical cancer.

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DNA Methylation and Hydroxymethylation in Cervical Cancer: Diagnosis, Prognosis and Treatment

Cited by 50 publications

References 88 publications

Epigenetic modification mechanisms involved in keloid: current status and prospect

Epigenetic modification mechanisms involved in keloid: current status and prospect

Artificial intelligence-assisted fast screening cervical high grade squamous intraepithelial lesion and squamous cell carcinoma diagnosis and treatment planning

Analysis of Therapeutic Targets and Prognostic Biomarkers of CXC Chemokines in Cervical Cancer Microenvironment

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