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One of the main causes of cancer-related mortality globally is Colorectal Cancer (CRC). The prognosis for advanced colorectal cancer is still not good, despite improvements in screening, early detection and therapy. Personalized medicine has demonstrated potential in enhancing results by customizing care according to unique patient attributes. The use of epigenetic alterations as predictive biomarkers is one area of personalized medicine that is gaining attention. The emergence and spread of cancer are significantly influenced by epigenetic alterations, such as DNA methylation, histone modifications and non-coding RNAs. The potential of epigenetic changes as predictive biomarkers in the treatment of colorectal cancer is examined in this essay, which also discusses their mechanics, clinical uses and future approaches.

Changes in gene expression that is heritable and independent of DNA sequence changes are referred to as epigenetic modifications [1]. Enticing targets for therapeutic intervention, these modifications are reversible and have the ability to control gene activity. Histone changes, DNA methylation and non-coding RNAs are the three primary categories of epigenetic alterations. DNA methylation is the process of adding a methyl group to cytosine residues at their 5' position; this usually occurs in CpG islands close to gene promoters. Tumor suppressor gene promoter hyper methylation can result in gene silence, which advances the development of cancer. On the other hand, hypo methylation can make oncogenes active. Gene transcription is regulated by histone changes that alter chromatin accessibility, such as acetylation, methylation, phosphorylation and ubiquitination. Noncoding RNAs, Including Long Non-Coding RNAs (lncRNAs) and microRNAs (miRNAs), can target mRNA transcripts for translational inhibition or degradation, hence modifying gene expression at the post-transcriptional level. As prognostic biomarkers for colorectal cancer, DNA methylation patterns have been thoroughly investigated. One characteristic of CRC is aberrant DNA methylation; numerous genes with altered methylation status have been found. For example, Microsatellite Instability (MSI), a subtype of Colorectal Cancer (CRC) with a high mutation rate, is linked to hyper methylation of the MLH1 gene promoter [2]. MLH1 methylation is a valuable biomarker for predicting treatment response since immune checkpoint drugs are effective in treating MSI-high colorectal cancers. The methylation of the Septin 9 (SEPT9) gene is an additional illustration. Since CRC frequently exhibits hyper methylation of the SEPT9 gene, its identification in blood plasma provides a non-invasive diagnostic for an early diagnosis. Additionally, resistance to specific chemotherapies has been associated with methylation of genes including SFRP2, APC and RASSF1A, which offers important information for treatment planning [3].

In CRC, histone alterations may also be prognostic indicators. These alterations can change gene expression and chromatin structure, which can impact how quickly cancer progresses and how well a treatment works. For instance, active transcription and open chromatin are linked to histone H3 acetylation at lysine 27 (H3K27ac). Higher levels of H3K27ac at particular gene promoters have been linked to improved prognosis and increased chemotherapeutic sensitivity [4]. Histone Deacetylase (HDAC) inhibitors have demonstrated effectiveness in treating colorectal cancer because they reverse histone deacetylation and encourage a more relaxed chromatin state. Histone acetylation status and HDAC expression levels can therefore act as biomarkers to predict how an individual will react to HDAC inhibitors [5]. Furthermore, gene silencing and tumor aggressiveness have been connected to the methylation state of histones, such as H3K4me3 (trimethylation at lysine 4) and H3K9me3 (trimethylation at lysine 9), offering additional information on the prognosis and therapy options for colorectal cancer. Non-coding RNAs are becoming more and more significant in CRC gene expression regulation; miRNAs and lncRNAs in particular. MiRNAs are single-stranded, short RNA molecules that bind to complementary regions on target mRNAs to suppress the expression of certain genes [6]. In CRC, dysregulation of miRNAs is frequent and can affect how well a treatment works. For instance, miR-21 is typically increased in colorectal cancer and is linked to resistance to chemotherapeutic drugs like 5-fluorouracil (5-FU). Poor response to chemotherapy and worse overall survival are predicted by high levels of miR-21 [7]. Longer non-coding RNA molecules (lncRNAs) can control the expression of genes by a number of methods, such as post-transcriptional processing, transcriptional regulation and chromatin remodeling. The development and spread of colorectal cancer have been linked to the long noncoding RNA HOTAIR (HOX transcript antisense RNA). Elevated HOTAIR expression may be a useful biomarker for treatment stratification because it is associated with a worse prognosis and resistance to chemotherapy [8]. The management of colorectal cancer may be greatly enhanced by the incorporation of epigenetic biomarkers into clinical practice. Epigenetic changes can offer important insights into tumor behavior, assisting in the prediction of treatment response and directing therapeutic choices. Immune checkpoint inhibitors, for example, may be beneficial for patients whose MLH1 promoter is hyper methylated, but patients whose miR-21 levels are increased may need to use different chemotherapeutic approaches to overcome resistance. Furthermore, new options for therapeutic intervention are made possible by the reversibility of epigenetic changes [9]. Medications that target histone modifications (like HDAC inhibitors) and DNA methylation (like DNA methyl transferase inhibitors) are either being studied or used in clinical settings. In order to maximize the effectiveness and reduce the negative effects of these medicines, it may be possible to identify patients who have particular epigenetic modifications [10].

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