Circulating Serum MiRNA-8074 as a Novel Prognostic Biomarker for Multiple Myeloma

Abstract

MiRNA-8074 is a molecule with the potential to regulate the expression of key genes related to the pathogenesis of multiple myeloma (MM), i.e., TP53, MYC, MAPK1, and KIAA. We analyzed the predictive and prognostic value of miRNA-8074 expression in MM patients. In total, 105 newly diagnosed MM patients treated with thalidomide (n = 27), bortezomib (n = 41) and bortezomib with thalidomide (n = 37) were studied. For miRNA analysis, the column method and the Real-Time PCR technique with specific TaqMan Fast Advanced Master Mix and TaqMan probes were used. Factors that were associated with a significant reduction in progression-free survival (PFS) included: ECOG > 1, ISS stage III, low hemoglobin, thrombocytopenia, hypoalbuminemia, abnormal renal function, elevated creatinine, GFR < 60 mL/min/1.73 m2, elevated LDH, del(17p), t(11;14), the use of a single drug regimen (thalidomide or bortezomib) and high miRNA-8074 expression (HR = 2.01, 95% CI: 1.16–3.49; p = 0.0233). In addition to the known prognostic factors, such as ECOG > 1, Durie–Salmon stage III, diagnosis of light chain disease or non-secreting MM, renal failure, hypoalbuminemia, hypercalcemia, high β2-microglobulin, elevated LDH, and t(14;16), a high expression of miRNA-8074 was significantly associated with a higher risk of death (HR = 4.12, 95% CI: 2.20–7.70; p = 0.0009). In summary, miRNA-8074 may be a useful diagnostic tool to assess the prognosis in MM patients.

Epigenetic Alterations as Vital Aspects of Bortezomib Molecular Action

“…The obtained results showed that a high expression of miR-8074 was associated with a worse clinical outcome, more precisely with a higher risk of death (HR = 4.12, 95% CI: 2.20–7.70; p = 0.0009) and with a significant reduction of PFS. This renders miR-8074 a useful tool for predicting the prognosis for MM patients [ 112 ]. Another non-coding RNA associated with clinical outcomes is miR-137.…”

“…More than 3.95% of total methylated DNA correlates with better OS. Szudy-Szczyrek et al [112] The high expression of miR-8074 is associated with a higher risk of death and shorter PFS in MM exposed to BTZ and THD. San-Miguel et al [113,114];…”

Role of Non-Coding RNAs in Diagnosis, Prediction and Prognosis of Multiple Myeloma

“…The prognostic value of overexpression of this miRNA for shorter PFS and OS was also confirmed (respectively: HR = 2.28, 95%CI = 1.07–4.91; HR = 3.97, 95%CI = 1.32–11.90). Additionally, the authors noticed a positive correlation between miR-8074 and MYC expression (rho = 0.476), which may explain the role of this miRNA in the development of MM [ 54 ]. The MYC gene has a confirmed role in the pathogenesis of MM by intensifying cell proliferation and migration (Notch and Wnt signaling pathways) and stimulating angiogenesis (via VEGF), and its increased activity is associated with tumor progression and occurs in up to 60% of disease cases [ 55 ].…”

Advances in Biomarkers for Multiple Myeloma

“…miRNA is a short (about 22 nucleotides long) non-coding RNA fragment with the ability to regulate gene expression at the post-transcriptional level [7] . It is involved in the occurrence and development of tumors.…”