Clinical implications of the genetics of sporadic colorectal cancer

Fischer, Jesse; Walker, Logan C.; Robinson, Bridget A.; Frizelle, Frank; Church, James M.; Eglinton, Tim

doi:10.1111/ans.15074

Cited by 29 publications

(14 citation statements)

References 42 publications

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“…Aging, high body mass index (BMI), positive smoking habit, extant polyposis, and inflammatory bowel disease (IBD) enhance the risk of colorectal cancer incidence (2)(3)(4)(5)(6) . Colorectal cancer is a heterogeneous disease with the majority of cases being sporadic (at least 80% of CRC patients) (7). However, there is a minor opulation that is categorized as an inherited group with specific genetic mutations.…”

Section: Introductionmentioning

confidence: 99%

Role of the NF-κB signaling pathway in the pathogenesis of colorectal cancer

Soleimani

Rahmani

Ferns

et al. 2020

Gene

162

111

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The NF-κB signaling pathway is a key regulator of CRC cell proliferation, apoptosis, angiogenesis, inflammation, metastasis, and drug resistance. Over-activation of the NF-κB pathway is a feature of colorectal cancer (CRC). While new combinatorial treatments have improved overall patient outcome; quality of life, cost of care, and patient survival rate have seen little improvement. Suppression of the NF-κB signaling pathway using biological or specific pharmacological inhibitors is a potential therapeutic approach in the treatment of colon cancer. This review summarizes the regulatory role of NF-κB signaling pathway in the pathogenesis of CRC for a better understanding and hence a better management of the disease.

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Section: Introductionmentioning

confidence: 99%

Role of the NF-κB signaling pathway in the pathogenesis of colorectal cancer

Soleimani

Rahmani

Ferns

et al. 2020

Gene

162

111

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“…Three canonical major distinct genetic pathways have been attributed to the development of sporadic CRC. These are not mutually exclusive and include the chromosomal instability pathway (CIN), the microsatellite instability pathway (MSI), and the CpG island methylator phenotype pathway (CIMP) [ 7 ]. The CIN pathway is the most frequent; it involves the classic adenoma-carcinoma sequence and genetic alterations in adenomatous polyposis coli—APC—(30–70%) and Kirsten Rat Sarcoma viral antigen homolog— KRAS —(30–50%).…”

Section: Introductionmentioning

confidence: 99%

miRNAs-Based Molecular Signature for KRAS Mutated and Wild Type Colorectal Cancer: An Explorative Study

Milanesi

Dobre

Bucuroiu

et al. 2020

Journal of Immunology Research

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microRNAs (miRNAs) have been proposed as promising molecular biomarkers for diagnosis, prognosis, and responsive therapeutic targets in different types of cancer, including colorectal cancer (CRC). In this study, we evaluated the expression levels of 84 cancer-associated miRNAs in a cohort of 39 human samples comprising 13 peritumoral and 26 tumoral tissues from surgical specimens of CRC patients. KRAS mutations were detected in 11 tumoral samples. In a first analysis, we found 5 miRNAs (miR-215-5p, miR-9-5p, miR-138-5p, miR378a-3p, and miR-150-5p) that were significantly downregulated and one upregulated (miR-135b-5p) in tumoral tissues compared with the peritumoral tissues. Furthermore, by comparing miRNA profile between KRAS mutated CRC tissues respect to wild type CRC tissues, we found 7 miRNA (miR-27b-3p, miR-191-5p, miR-let7d-5p, miR-15b-5p, miR-98-5p, miR-10a-5p, and miR-149-5p) downregulated in KRAS mutated condition. In conclusion, we have identified a panel of miRNAs that specifically distinguish CRC tissues from peritumoral tissue and a different set of miRNAs specific for CRC with KRAS mutations. These findings may contribute to the discovering of new molecular biomarkers with clinic relevance and might shed light on novel molecular aspects of CRC.

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“…With the exception of patients with a family history, the majority of cases of CRC are sporadic (22). Although the mortality of this malignancy has been markedly decreased following the introduction of routine examinations, its incidence remains high (23).…”

Section: Discussionmentioning

confidence: 99%

Application of weighted gene co‑expression network analysis to explore the potential diagnostic biomarkers for colorectal cancer

et al. 2020

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colorectal cancer (crc) is one of the most common malignant diseases in the world. although mechanistic studies have been conducted on the pathogenesis of crc, the molecular mechanism of crc tumorigenesis remains unclear. in the present study, the weighted gene co-expression network analysis was performed for the Gene expression omnibus (Geo) dataset GSe87211, in order to analyze the key modules involved in the pathogenesis of crc. next, Gene ontology and Kyoto encyclopedia of Genes and Genomes enrichment analyses were performed on the key module genes to analyze the functional pathways involved. The hub genes were screened using the Cytoscape platform and verified by a second Geo dataset, GSe21510. Finally, 10 hub genes were identified in 2 key modules (the green and brown modules) as the genes most significantly associated with the tumorigenesis of crc. The 5 hub genes from the green module included collagen type i α1 chain, collagen type Xii α1 chain, collagen triple helix repeat containing 1, inhibin subunit βa (INHBA) and chromobox 2 (CBX2), while the 5 hub genes from the brown module included bestrophin 2 (BEST2), carbonic anhydrase 2, glucagon, solute carrier family 4 member 4 and gliomedin. The 2 key modules with the 10 hub genes identified may regulate the occurrence and development of crc through the extracellular matrix pathway, Pi3K-akt and chemokine signaling pathways, thus providing a reference for understanding the complex mechanism of tumorigenesis in crc. of note, few studies have reported the pathogenesis of crc with the 3 identified hub genes, INHBA, CBX2 and BEST2. Further investigation of the molecular mechanism of these genes in crc is recommended.

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Clinical implications of the genetics of sporadic colorectal cancer

Cited by 29 publications

References 42 publications

Role of the NF-κB signaling pathway in the pathogenesis of colorectal cancer

Role of the NF-κB signaling pathway in the pathogenesis of colorectal cancer

miRNAs-Based Molecular Signature for KRAS Mutated and Wild Type Colorectal Cancer: An Explorative Study

Application of weighted gene co‑expression network analysis to explore the potential diagnostic biomarkers for colorectal cancer

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