Epigenetics: The Key to Future Diagnostics and Therapeutics of Lung Cancer

Jha, Gaurav; Azhar, Sabeen; Rashid, Usman; Khalaf, Hasan; Alhalabi, Noor; Ravindran, Deepthi; Ahmad, Rawaha

doi:10.7759/cureus.19770

Cited by 4 publications

(5 citation statements)

References 33 publications

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“…Apart from the synergistic action of mutations in oncogenes and tumor suppressor genes, it has been increasingly recognized that epigenetic changes are another major driver of cancer initiation and development [93,94], which often include DNA methylation, histone modi cation, chromatin remodeling, and alteration of post-transcriptional regulators. Despite these challenges, studies on the epigenetic pathogenesis of lung cancer have made remarkable progress over the past 10 years, among which the most studied is the role of DNA methylation in early diagnosis, e cacy assessment, risk strati cation, and prognosis estimation [95][96][97]. Speci cally, DNA hypermethylation of the promoter region of miR-126-3p promotes LUAD progression, and biomimetic nanoparticles based on matrix metalloproteinase-2stimulated peptide-binding miR-126-3p suppress tumor growth and metastasis [98].…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms and prognostic value of the selenoprotein gene family in lung adenocarcinoma and lung squamous cell carcinoma

Tian

Luo

et al. 2023

Preprint

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Lung cancer is the leading cause of cancer-related deaths worldwide, and has the highest morbidity among all cancers. Non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases and its most common subtypes are lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Although the selenium protein gene plays a key role in the initiation, development, and progression of many cancers, the panoramic picture of the involvement of selenoprotein gene family in LUAD and LUSC is unclear. Therefore, the expression and prognostic value of the selenoprotein family genes, as well as their potential mechanisms in LUAD and LUSC, were systematically examined in this study. First, differential expression and survival analyses revealed that a high expression of glutathione peroxidase 2 (GPX2) and low expression of both GPX3 and selenoprotein P (SELENOP) in tumors correlated with poor overall survival in patients with LUAD, while a high expression of iodothyronine deiodinase 2 (DIO2) in tumors correlated with better overall survival, and a low expression of GPX3 correlated with poor overall survival in patients with LUSC. Next, we developed a nomogram based on the Cox regression model to visualize survival and confirmed its predictive capability. Methylation, gene mutation, and immune infiltration analyses of selenoprotein genes indicated that they all participated in the progression of LUAD and LUSC. Enrichment analysis and protein–protein interaction networks showed that the common differentially expressed genes mainly participated in selenocompound metabolism, glutathione metabolism, arachidonic acid metabolism, and thyroid hormone synthesis. In addition, we constructed transcription factor (TF)-mRNA, mRNA-RNA-binding protein (RBP), and mRNA-drug regulatory networks. Our research shows that selenoprotein family members have potential as novel biomarkers for prognostic assessment and as therapeutic targets for LUAD and LUSC.

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Section: Discussionmentioning

confidence: 99%

Molecular mechanisms and prognostic value of the selenoprotein gene family in lung adenocarcinoma and lung squamous cell carcinoma

Tian

Luo

et al. 2023

Preprint

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“…For stage IV NSCLC which is advanced and mostly considered as incurable, ablative surgery may be helpful in patients with oligometastatic disease and has shown prolonged survival benefits. Per European consensus, synchronous oligometastases is defined as up to five distant metastases in a maximum of three organs based on comprehensive imaging including a PET scan and brain MRI ( 51 ).…”

Section: Systemic Therapymentioning

confidence: 99%

“…They include high level MET amplification and ERBB2 (HER2) mutations. The future of LC is strongly focused on epigenetics which encompasses DNA methylation, microRNAs, histone modifications, copious reinforcing signals, and chromatin modeling ( 51 ). On the other hand, a combination of RT and immunotherapy is an interesting field of study at this time.…”

Section: Future Perspectivementioning

confidence: 99%

A snapshot of lung cancer: where are we now?—a narrative review

Ibodeng¹,

Uche²,

Mokua³

et al. 2023

Ann Transl Med

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Background and Objective: The global impact of cancer and cancer-related deaths has been a huge challenge and continues to be a setback in the health sector and beyond even in recent times. Cancer is the second leading cause of death globally with lung cancer (LC) being the second most prevalent malignancy and the leading cause of mortality amongst cancers in men and women worldwide. LC still constitutes a major burden despite recent advances in diagnostic and treatment tools. In this article, we review the trends in LC with an emphasis on non-small cell LC. We aimed to identify nuclear and mitochondrial genetic alterations, microbiome dysbiosis, and their significance in non-small cell LC tumorigenesis as well as its relevance in the future management of LCs. Methods:We identified studies for this review by searching the PubMed, Cochrane, Education Resources Information Center (ERIC), and Surveillance, Epidemiology, and End Results (SEER) databases for English-

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“…Epigenetic alterations have been detected in all human cancers, and these changes, including DNA methylation, play an important role in the early development and progression of diseases, particularly cancer ( 7 ). The DNA methylation of intermittently distributed CpG sites down-regulates the expression of tumor suppressor genes.…”

Section: Introductionmentioning

confidence: 99%

Aberrant methylation of dipeptidyl peptidase‑like 6 as a potential prognostic biomarker for lung adenocarcinoma

et al. 2023

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We previously performed the genome-wide screening of aberrantly methylated CpG islands (CGIs) using the paired tumorous and non-tumorous tissues of 12 lung adenocarcinomas (LADC). In comparisons with paired normal lung tissues, dipeptidyl peptidase-like 6 (DPP6) has been identified as the most significantly hypermethylated CGI in LADC. DPP6 is a protein that modulates A-type potassium channels in the somatodendritic compartments of neurons, which play a role in synaptic plasticity. Previous studies have showed that DPP6 is downregulated in cancers, such as acute myeloid leukemia and melanoma, but upregulated in colon cancer, which is attributed to hyper-and hypomethylation, respectively. The present study investigated the methylation and expression levels of DPP6 and its prognostic value in patients with LADC. The DNA methylation and mRNA expression levels of DPP6 in surgically resected LADC tissues were examined by bisulfite pyrosequencing and reverse transcription-quantitative PCR, respectively. The DNA methylation and mRNA expression levels of DPP6 were both significantly higher in LADC tissues compared with in normal lung tissues (n=25; P<0.0001). Overall and disease-free survival rates were significantly higher in LADC with high mRNA expression levels compared with those with low levels. In conclusion, epigenetic alterations in DPP6 were significantly higher in LADC tissues compared with in normal lung tissues, which may contribute to the malignant features and worse prognosis of these patients.

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Epigenetics: The Key to Future Diagnostics and Therapeutics of Lung Cancer

Cited by 4 publications

References 33 publications

Molecular mechanisms and prognostic value of the selenoprotein gene family in lung adenocarcinoma and lung squamous cell carcinoma

Molecular mechanisms and prognostic value of the selenoprotein gene family in lung adenocarcinoma and lung squamous cell carcinoma

A snapshot of lung cancer: where are we now?—a narrative review

Aberrant methylation of dipeptidyl peptidase‑like 6 as a potential prognostic biomarker for lung adenocarcinoma

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