Page 83 - TD-4-1
P. 83

Tumor Discovery                                               Colorectal cancer: miRNA, mRNA, protein insights



            P  <  0.0001),  TGFBRII  I  (r  =  0.708,  P  <  0.0001),  BCL2   Table 4. Association between mRNAs and target genes
            (r = 0.623, P < 0.0001), and RASA1 (r = 0.728, P < 0.0001).   (mRNA and protein)
            No correlation was observed between mRNA and protein   Variable  TGFBRII   TGFBRII   RASA1   RASA1
            levels of PTEN (r = −0.085, P = 0.450), and KLF4 (r = 0.114,   mRNA      protein  mRNA     protein
            P = 0.313).
                                                               miR-21 CC    −0.358   −0.328
            3.4. Association the expression of biomarkers      P            0.001     0.003
            (target genes) and miRNAs                          miR-29a CC                      −0.217   −0.222
                                                               P                                0.01    0.004
            Spearman’s rank-order correlation was performed to   miR-31 CC                     −0.276   −0.209
            evaluate the relationship between the markers examined in   P                       0.01     0.01
            this study. High expression levels of miR-21 and miR-224   miR-224 CC  −0.276  −0.319
            were found to be associated with lower levels of TGFBRII   P    0.01      0.004
            mRNA (r = −0.358, P = 0.001; and r = −0.276, P = 0.01,   Abbreviation: CC: Correlation coefficient; mRNA: microRNAs.
            respectively)  as well as  TGFBRII  protein  (r  =  −0.328,
            P =  0.003; and r = −0.319,  P = 0.004, respectively).   Table 5. Association between microRNAs
            Furthermore, increased expression of both miR-29a and
            miR-31 showed an inverse correlation with RASA1 mRNA   Variables  miR‑29a  miR‑31  miR‑92a  miR‑224
            levels (r =  −0.217,  P = 0.01; and r = −0.276,  P  =  0.01,   miR-20a CC  0.380  0.403
            respectively)  and  RASA1  protein  levels  (r  =  −0.222,   P  0.0001   0.0001
            P = 0.004; and r = −0.209, P = 0.01, respectively) (Table 4).   miR-21 CC  0.526  0.285
            A significant correlation was also observed between miR-  P    0.0001    0.01
            20a and miR-29 (r = 0.380, P = 0.0001) as well as miR-31   miR-29a CC    0.275     0.324
            (r = 0.403, P = 0.0001). In addition, a notable correlation   P          0.01      0.003
            was found between miR-21 and miR-29a (r = 0.526,   miR-31 CC                                0.328
            P = 0.0001) and miR-31 (r = 0.285, P = 0.01). Moreover, a   P                               0.003
            strong correlation was noted between miR-29a and miR-31   miR-92a CC                        0.382
            (r = 0.275, P = 0.01) and miR-92a (r = 0.324, P = 0.003).   P                               0.0001
            Significant correlations were also observed between miR-  Abbreviation: CC: Correlation coefficient.
            31 and miR-224 (r = 0.328, P = 0.003) and between miR-
            92a and miR-224 (r = 0.382, P = 0.0001) (Table 5).   Despite the relatively small sample size, we explored
                                                               clinical associations, though no significant correlations
            4. Discussion                                      between miRNA expression and clinicopathological
            CRC remains a significant global health burden, with   features were identified. This is contrary to findings by
            substantial morbidity and mortality rates worldwide.   others, such as Schepeler et al.  who reported increased
                                                                                        31
            Unraveling  the  intricate  molecular  mechanisms  miR-31 levels in stage IV tumors, and Zhou et al.  who
                                                                                                        32
            underlying CRC pathogenesis is crucial for advancing   observed a  correlation  between miR-92a expression and
            our understanding of the disease and identifying novel   advanced clinical stage.
            therapeutic targets and diagnostic biomarkers. In this   In addition, our study identified potential mRNA
            comprehensive study, we employed a multidimensional
            approach, integrating miRNA quantification, mRNA   targets of dysregulated miRNAs in CRC. Through mRNA
            profiling, and protein evaluation, to evaluate their potential   quantification analysis, we observed differential expression
            as biomarkers for CRC detection.                   patterns of genes involved in critical signaling pathways
                                                               dysregulated in  CRC. Specifically,  RASA1 and  TGFBRII,
              The dysregulation of miRNAs, small non-coding RNAs   tumor suppressor genes in Ras and TGF-β pathways,
            that modulate gene expression, is a hallmark of CRC   respectively,  were  significantly  downregulated  in  CRC
            tumorigenesis. 26,27  Our study revealed abnormal expression   tissues. 33,34  Conversely,  BCL2, an anti-apoptotic gene,
            patterns of several miRNAs in CRC tissues compared to   showed upregulation in CRC samples, consistent with its
            adjacent normal mucosa. Notably, miR-31, miR-29a, miR-  role in promoting cell survival and chemoresistance. 35
            21, and miR-20a were significantly upregulated in CRC
            samples, indicating their roles as oncogenic drivers in CRC   The immunohistochemical evaluation of target protein
            progression. 28-30  These findings support the growing evidence   expression provided further insights into the molecular
            implicating these miRNAs in CRC pathogenesis and highlight   alterations within CRC tissues. The observed heterogeneity
            their potential as diagnostic and prognostic biomarkers.  in protein expression patterns underscores the dynamic


            Volume 4 Issue 1 (2025)                         75                                doi: 10.36922/td.4631
   78   79   80   81   82   83   84   85   86   87   88