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Tumor Discovery Colorectal cancer: miRNA, mRNA, protein insights

related deaths. In recent years, there has been a notable instance, FOLFOX resistance in advanced CRC is linked
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emergence of new favorable subsets of cancers of unknown to the altered expression of serum miRNAs, such as
primary origin, including CRC of unknown origin. This miR-19a. In metastatic CRC, miR-126 upregulation has
new clinical entity is treated as CRC and has contributed been associated with resistance to bevacizumab, while
to the rising incidence rates of CRC. Understanding overexpression of miR-31, miR-100, and miR-125b, along
these trends is crucial, as they may influence the with miR-7 downregulation, correlates with resistance to
sociodemographic factors and clinical aspects that cetuximab. 10
ultimately affect the quality of life in patients undergoing In this study, we have selected a panel of six miRNAs
surgical treatment for CRC. There is significant evidence (miR-20a, miR-21, miR-29a, miR-31, miR-92a, and miR-
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affirming the vital role of screening and early detection 224), previously implicated in CRC and proposed as
in combating CRC, effectively reducing its incidence and
mortality rates. For example, the 5-year survival rate is diagnostic and prognostic markers. These miRNAs have
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as high as 93.2% for TNM stage I as compared to only shown promise in CRC research, with multiple studies
8.1% for stage IV. However, existing screening tools such highlighting their dysregulation and potential clinical
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11-16
as (i) colonoscopy screening, which is currently the most significance. For instance, Sun et al. showed that
reliable screening tool, has been hampered because of miR-31 significantly contributes to the activation of the
its invasive nature and high cost; and (2) the fecal occult RAS signaling pathway by inhibiting the translation of
blood test, which has low sensitivity and requires dietary RASA1. This action enhances the growth of CRC cells and
restriction, impedes compliance and use. In addition, promotes tumor development. MiR-92a has been found
studies have investigated several molecular biomarkers to be upregulated in CRC and associated with tumor
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for CRC detection, such as carcinoembryonic antigen growth, migration and invasion via suppression of PTEN.
(CEA), and shown that high CEA levels are associated MiR-29a has been associated with CRC progression and
with CRC progression. However, its utility in the disease poor prognosis, acting by downregulating genes involved
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screening is limited due to the serum level of CEA not in apoptosis and extracellular matrix remodeling. Our
being elevated after the tumor has invaded the serosa experiments suggest that miR-20a disrupts the homeostasis
membrane. 5,6 of the colonic epithelium by interfering with the regulation
of Myc/p21 by transforming growth factor beta (TGF-β),
Given these factors, there is a pressing need for specific a process that is crucial for malignant transformation.
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molecular markers to improve the diagnosis of CRC. Colorectal tumors with elevated levels of miR-21 exhibited
Recently, researchers have concentrated on microRNAs microsatellite instability and demonstrated a diminished
(miRNAs) because of their involvement in essential cellular response to 5-fluorouracil-based chemotherapy, Our
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processes such as development, cell cycle advancement, investigation aims to elucidate whether this miRNA
differentiation, proliferation, and apoptosis. Aberrant panel: (i) orchestrates the activation of common signaling
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expression of miRNAs, which function as either tumor pathways pivotal in CRC carcinogenesis, as gauged by
suppressors or oncogenes, has been implicated in various mRNA and protein expression levels of genes targeted
cancers. Moreover, miRNAs exhibit discriminatory by these miRNAs, and (ii) holds potential as screening
potential across cancer types, predicting outcomes in biomarkers for CRC.
hematological and solid malignancies. Notably, the
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differential expression of miRNAs between CRC tumors 2. Methods
and adjacent normal tissue underscores their promise in
early diagnostic and prognostic applications. 9 2.1. Selection criteria

Biomarker testing is now a standard part of CRC In this study, we utilized paired formalin-fixed paraffin-
investigation, particularly regarding major genetic embedded (FFPE) cases, consisting of primary CRC
mutations like RAS, which are associated with tumor tissues and corresponding normal mucosa samples
aggressiveness and chemotherapy response. In addition, obtained from 81 patients. The normal tissue specimens
growing evidence indicates that inflammation contributes comprised margin blocks and tissue immediately adjacent
to CRC progression, prompting studies on the predictive to the tumor, exclusively sourced from mucosal tissue.
and prognostic roles of various blood-based inflammatory All patients underwent surgical procedures at Queen’s
markers, such as the neutrophil–lymphocyte ratio, Medical Centre (QMC) in Nottingham, United Kingdom,
lymphocyte–monocyte ratio, and platelet–lymphocyte between 2012 and 2014. Case selection criteria included
ratio. Furthermore, miRNAs act as both tumor suppressors the availability of comprehensive clinicopathological data
and oncogenes, with ongoing research exploring their and the presence of at least 50% tumor cells in the tumor
diagnostic, prognostic, and predictive implications. For block. Notably, all tissue samples analyzed in this study

Volume 4 Issue 1 (2025) 69 doi: 10.36922/td.4631