Integrated analysis of multi-omics data for the discovery of biomarkers and therapeutic targets for colorectal cancer

Zafari, Nima; Bathaei, Parsa; Velayati, Mahla; Khojasteh-Leylakoohi, Fatemeh; Khazaei, Majid; Fiuji, Hamid; Nassiri, Mohammadreza; Hassanian, Seyed Mahdi; Ferns, Gordon A.; Nazari, Elham; Avan, Amir

doi:10.1016/j.compbiomed.2023.106639

Cited by 19 publications

(14 citation statements)

References 150 publications

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“…Despite recent advancements in treatment, colorectal cancer still has a poor prognosis in advanced stages, indicating we must develop therapeutic targets in order to improve patient outcomes [ 34 ]. The identification of novel biomarkers and therapeutic targets is therefore crucial to improving the prognosis of colorectal cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Development and validation of epigenetic modification-related signals for the diagnosis and prognosis of colorectal cancer

Li,

et al. 2024

BMC Genomics

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Background Colorectal cancer (CRC) is one of the world's most common malignancies. Epigenetics is the study of heritable changes in characteristics beyond the DNA sequence. Epigenetic information is essential for maintaining specific expression patterns of genes and the normal development of individuals, and disorders of epigenetic modifications may alter the expression of oncogenes and tumor suppressor genes and affect the development of cancer. This study elucidates the relationship between epigenetics and the prognosis of CRC patients by developing a predictive model to explore the potential value of epigenetics in the treatment of CRC. Methods Gene expression data of CRC patients’ tumor tissue and controls were downloaded from GEO database. Combined with the 720 epigenetic-related genes (ERGs) downloaded from EpiFactors database, prognosis-related epigenetic genes were selected by univariate cox and LASSO analyses. The Kaplan–Meier and ROC curve were used to analyze the accuracy of the model. Data of 238 CRC samples with survival data downloaded from the GSE17538 were used for validation. Finally, the risk model is combined with the clinical characteristics of CRC patients to perform univariate and multivariate cox regression analysis to obtain independent risk factors and draw nomogram. Then we evaluated the accuracy of its prediction by calibration curves. Results A total of 2906 differentially expressed genes (DEGs) were identified between CRC and control samples. After overlapping DEGs with 720 ERGs, 56 epigenetic-related DEGs (DEERGs) were identified. Combining univariate and LASSO regression analysis, the 8 epigenetic-related genes-based risk score model of CRC was established. The ROC curves and survival difference of high and low risk groups revealed the good performance of the risk score model based on prognostic biomarkers in both training and validation sets. A nomogram with good performance to predict the survival of CRC patients were established based on age, NM stage and risk score. The calibration curves showed that the prognostic model had good predictive performance. Conclusion In this study, an epigenetically relevant 8-gene signature was constructed that can effectively predict the prognosis of CRC patients and provide potential directions for targeted therapies for CRC.

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Section: Discussionmentioning

confidence: 99%

Development and validation of epigenetic modification-related signals for the diagnosis and prognosis of colorectal cancer

Li,

et al. 2024

BMC Genomics

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“…Integrating MSI or dMMR testing into the diagnostic process helps identify patients who are more likely to benefit from immunotherapy, underscoring the importance of these biomarkers in guiding treatment decisions. 172 Moreover, the integration of multiple biomarker tests is becoming increasingly common in precision medicine for colorectal cancer. Comprehensive molecular profiling that assesses a range of biomarkers, such as RAS mutation status, MSI/dMMR, HER2 amplification, and others, provides a more holistic view of the tumor's genetic landscape.…”

Section: Integration Of Biomarkermentioning

confidence: 99%

“…Tumors with high MSI or dMMR are more likely to respond to immune checkpoint inhibitors such as programmed cell death protein 1 (PD-1) inhibitors. Integrating MSI or dMMR testing into the diagnostic process helps identify patients who are more likely to benefit from immunotherapy, underscoring the importance of these biomarkers in guiding treatment decisions . Moreover, the integration of multiple biomarker tests is becoming increasingly common in precision medicine for colorectal cancer.…”

Section: Challenges and Considerations In Precision Medicine Implemen...mentioning

confidence: 99%

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

Kiran,

Yashaswini,

Maheshwari

et al. 2024

ACS Pharmacol. Transl. Sci.

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Precision medicine is transforming colorectal cancer treatment through the integration of advanced technologies and biomarkers, enhancing personalized and effective disease management. Identification of key driver mutations and molecular profiling have deepened our comprehension of the genetic alterations in colorectal cancer, facilitating targeted therapy and immunotherapy selection. Biomarkers such as microsatellite instability (MSI) and DNA mismatch repair deficiency (dMMR) guide treatment decisions, opening avenues for immunotherapy. Emerging technologies such as liquid biopsies, artificial intelligence, and machine learning promise to revolutionize early detection, monitoring, and treatment selection in precision medicine. Despite these advancements, ethical and regulatory challenges, including equitable access and data privacy, emphasize the importance of responsible implementation. The dynamic nature of colorectal cancer, with its tumor heterogeneity and clonal evolution, underscores the necessity for adaptive and personalized treatment strategies. The future of precision medicine in colorectal cancer lies in its potential to enhance patient care, clinical outcomes, and our understanding of this intricate disease, marked by ongoing evolution in the field. The current reviews focus on providing in-depth knowledge on the various and diverse approaches utilized for precision medicine against colorectal cancer, at both molecular and biochemical levels.

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“…Animal models of various cancers and clinical studies showed that there is a causal relationship between miRNAs and cancer development, and as a result, miRNAs quickly entered the clinical stage as biomarkers and therapeutic targets. [42][43][44][45] miRNAs can act as promoters or tumor suppressors to induce resistance to chemo/radiotherapy in cancer through DNA damage repair and the inhibition of apoptosis. 46 The target of miRNAs can be a tumor suppressor gene.…”

Section: Mirnas In Cancer Therapymentioning

confidence: 99%

“…An aberrant expression of one miRNA can affect hundreds of mRNAs and has a profound effect on cancer‐related signaling pathways. Animal models of various cancers and clinical studies showed that there is a causal relationship between miRNAs and cancer development, and as a result, miRNAs quickly entered the clinical stage as biomarkers and therapeutic targets 42–45 . miRNAs can act as promoters or tumor suppressors to induce resistance to chemo/radiotherapy in cancer through DNA damage repair and the inhibition of apoptosis 46 .…”

Section: Mirnas In Cancer Therapymentioning

confidence: 99%

Bioengineered chimeric tRNA/pre‐miRNAs as prodrugs in cancer therapy

Rafieenia,

Ebrahimi,

Emadi

et al. 2023

Biotechnology Progress

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Today, biologic prodrugs have led to targeting specific tumor markers and have increased specificity and selectivity in cancer therapy. Various studies have shown the role of ncRNAs in cancer pathology and tumorigenesis and have suggested that ncRNAs, especially miRNAs, are valuable molecules in understanding cancer biology and therapeutic processes. Most miRNAs‐based research and treatment are limited to chemically synthesized miRNAs. Synthetic alterations in these miRNA mimics may affect their folding, safety profile, and even biological activity. However, despite synthetic miRNA mimics produced by automated systems, various carriers could be used to achieve efficient production of bioengineered miRNAs through economical microbial fermentation. These bioengineered miRNAs as biological prodrugs could provide a new approach for safe therapeutic methods and drug production. In this regard, bioengineered chimeric miRNAs could be selectively processed to mature miRNAs in different types of cancer cells by targeting the desired gene and regulating cancer progression. In this article, we aim to review bioengineered miRNAs and their use in cancer therapy, as well as offering advances in this area, including the use of chimeric tRNA/pre‐miRNAs.

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Integrated analysis of multi-omics data for the discovery of biomarkers and therapeutic targets for colorectal cancer

Cited by 19 publications

References 150 publications

Development and validation of epigenetic modification-related signals for the diagnosis and prognosis of colorectal cancer

Development and validation of epigenetic modification-related signals for the diagnosis and prognosis of colorectal cancer

Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies

Bioengineered chimeric tRNA/pre‐miRNAs as prodrugs in cancer therapy

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