Abstract
Object: This study aims to clarify the expression of plasma miRNA in CRC patients, and to clarify the potential use of these miRNAs in diagnosis and prognosis, and to establish a prognostic model to initially explore its clinical value. Methods: We detected the expression of 6 miRNAs in normal colon epithelial cell lines and colorectal cancer cell lines by qRT-PCR and they were validated in the tissues of three subtypes: 20 healthy subjects, 41 pCRC and 49 mCRC patients. COX regression and ROC analyses use to evaluate the diagnostic and prognostic efficacy of candidate miRNAs. Subsequently, we initially established a nomogram prognostic model. MiRNA is also used to construct miRNA-mRNA interaction network and PPI network modules. Results: Five miRNAs showed significant differential expression in pCRC, mCRC patients and normal groups. ROC analysis showed that CEA, miR-96, miR-99b and miR-96/miR-99b are distinguishable from pCRC and mCRC patients, with AUC ranging from 0.65 to 0.91; among them, the ratio of miR-96/miR-99b is stronger than any diagnostic indicators, such as CEA and CA125. Multivariate survival analysis identified miR-96, miR-99b, N stage, M stage and clinical stage as independent prognostic indicators of mCRC. The nomogram based on these 5 characteristics has satisfactory prognostic values. Conclusion: Our data indicate that plasma miR-96/miR-99b can be used as a promising biomarker for early detection of mCRC patients; our nomogram has a promising evaluation value.
Highlights
Colorectal cancer (CRC) is one of the leading causes of cancerrelated deaths (Sung et al, 2021)
We detected the expression of 6 miRNAs in normal colon epithelial cell lines and colorectal cancer cell lines by Quantitative real-time polymerase chain reaction (qRT-PCR) and they were validated in the tissues of three subtypes: 20 healthy subjects, 41 Primary colorectal cancer (pCRC) and 49 Metastatic colorectal cancer (mCRC) patients
Receiver operator characteristic (ROC) analysis showed that CEA, miR-96, miR-99b and miR-96/miR99b are distinguishable from pCRC and mCRC patients, with AUC ranging from 0.65 to 0.91; among them, the ratio of miR-96/miR-99b is stronger than any diagnostic indicators, such as CEA and CA125
Summary
Colorectal cancer (CRC) is one of the leading causes of cancerrelated deaths (Sung et al, 2021). The occurrence of colorectal liver metastasis (mCRC) is a multi-factor and multi-step process. Most patients with mCRC are not suited for radical resection surgery with its characteristic low five-year-survival rate ≤10% (Manfredi et al, 2006). Common strategies, such as laparoscopy, fine needle aspiration cytology and imaging modalities, such as enhanced computed tomography (CT), magnetic resonance imaging (MRI), are either invasive, characterized by a high degree of complication or the insufficiency of typical symptoms or signs (Metcalfe et al, 2004). Due to the limitations of CEA, we urgently require more effective biomarkers for mCRC
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