piRNA-823 Is a Unique Potential Diagnostic Non-Invasive Biomarker in Colorectal Cancer Patients

Abstract

Early detection of colorectal cancer (CRC) is the most important factor in deciding its prognosis, so the need to develop an accurate screening test is a must. P-element induced wimpy testis (PIWI) RNA-823 (piR-823) is one of the first piRNAs recognized to be linked to malignancy. We aimed to investigate the expression levels of piR-823 in both serum and tissues of colorectal cancer patients and the ability to use its serum level as a non-invasive diagnostic biomarker to detect colorectal cancer. We determined piR-823 expression levels in 84 serum samples of CRC patients, 75 serum samples of healthy controls, and biological specimens obtained from the 84 patients with colorectal cancer from both the tumor tissues and the normal neighboring tissues using quantitative real-time reverse transcriptase-PCR. We showed that piR-823 had significantly higher serum and tissue expression levels in CRC patients compared to the controls. We observed a significant positive correlation between piR-823 serum levels and the staging of CRC, with significantly higher levels exhibiting advanced stages of CRC (III and IV). This translates into poorer differentiation and lymph node metastasis. The receiver operating characteristic curve (ROC curve) test showed 83.3% sensitivity and 89.3% specificity at a cut-off value of >5.98-fold change, with an area under the curve of 0.933 (p < 0.0001) concerning the ability of piR-823 in diagnosing patients with colorectal carcinoma. piR-823 expression is upregulated in colorectal cancer patients’ serum and tissues, and it can be used as a diagnostic noninvasive biomarker for CRC.

PIWI-Interacting RNAs (piRNAs): Promising Applications as Emerging Biomarkers for Digestive System Cancer

“…In breast cancer, the levels of piR-4987 are positively correlated with lymph node metastasis (Huang et al, 2013). In addition, piR-823 expression is 2-fold higher in poorly differentiated colorectal cancer (CRC) tissues than in well/moderately-differentiated CRC tissues (Sabbah et al, 2021). The upregulation of piR-823 is associated with the presence of distant metastasis in gastric cancer (GC) patients (Cui et al, 2011).…”

“…By using pulldown assay or reporter assay, those molecules that interact with piRNAs (proteins or RNAs) could be determined. (Cui et al, 2011;Sabbah et al, 2021). The aberrant piRNA expression affects the tumorigenesis and progression of digestive system cancers (Figures 2, 3).…”

The Emerging Role of PIWI-Interacting RNAs (piRNAs) in Gastrointestinal Cancers: An Updated Perspective

“…For instance, Sabbah et al evaluated the serum levels of piR-823 as a non-invasive diagnostic biomarker to detect CRC cases, finding that this piRNA was significantly increased in the serum of CRC patients compared to those samples from healthy donors. The ROC curve showed an AUC value of 0.933 for piR-823 (83.3% sensitivity and 89.3% specificity) [ 67 ], which reaffirms the idea that this piRNA not only could be considered a promising prognostic marker and therapeutic target for colorectal neoplasia but also could be used as a biomarker to detect this malignancy in the future.…”

“…In the case of tissue samples, the authors confirmed the overexpression of piR-823 in CRC tissues and its association with those poorly differentiated tumors. In addition, they also found that higher piR-823 levels were associated with advanced TNM stages (III–IV) [ 67 ]. Therefore, both studies suggest that piR-823 can act as a potential prognostic marker and as a promising therapeutic target for CRC [ 66 , 67 ].…”

“…In addition, they also found that higher piR-823 levels were associated with advanced TNM stages (III–IV) [ 67 ]. Therefore, both studies suggest that piR-823 can act as a potential prognostic marker and as a promising therapeutic target for CRC [ 66 , 67 ]. Sabbah et al also studied piR-823 as a potential diagnostic biomarker in CRC and their results will be shown later.…”