Lncrna ANGPTL1-3 and its target microRNA-30a exhibit potency as biomarkers for bortezomib response and prognosis in multiple myeloma patients

ABSTRACT

Objective: Long non-coding RNA ANGPTL1-3 (lnc-ANGPTL1-3) is previously observed to induce bortezomib resistance via targeting microRNA-30a (miR-30a) in multiple myeloma (MM). Hence, this study aimed to further explore the relationship between lnc-ANGPTL1-3 and miR-30a and their linkage with disease properties and prognosis in bortezomib-treated MM patients.

Methods: Fifty-nine MM patients underwent treatment with the bortezomib-based regimen, and 30 healthy donors were consecutively enrolled. Bone marrow samples were collected from MM patients (before therapy) and healthy donors; then, plasma cells were separated for lnc-ANGPTL1-3 and miR-30a detection by RT-qPCR. Then treatment response, progression-free survival (PFS), and overall survival (OS) of MM patients were assessed.

Results: Lnc-ANGPTL1-3 was upregulated while miR-30a was downregulated in MM patients compared to healthy donors (both P < 0.001), then a negative correlation between lnc-ANGPTL1-3 and miR-30a was found in MM patients (P < 0.001) instead of in health donors (P = 0.188). In MM patients, lnc-ANGPTL1-3 correlated with increased t (4;14) (P = 0.033), Del (17p) (P = 0.018), ISS stage (P = 0.020), R-ISS stage (P = 0.025) but not t (14;16) (P = 0.255) or Durie-Salmon stage (P = 0.186); while miR-30a only related to decreased t (14;16) (P = 0.025) and R-ISS stage (P = 0.006). Besides, lnc-ANGPTL1-3 predicted lower complete response (CR) (P = 0.034), poor PFS (P = 0.016) and OS (P = 0.041) but not objective response rate (ORR) (P = 0.128). However, miR-30a forecasted higher CR (P = 0.013), prolonged PFS (P = 0.014), and OS (P = 0.045) but not ORR (P = 0.407).

Conclusion: Lnc-ANGPTL1-3 negative correlates with miR-30a, which links with key cytogenetic features, ISS/R-ISS stage, and prognosis in MM patients who underwent treatment of bortezomib-based regimen.

KEYWORDS:

• Multiple myeloma
• lnc-ANGPTL1-3
• miR-30a
• treatment response
• survival

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by the Expression and significance of PI3k/Akt signal molecules in multiple myeloma stem cells (YQ15B01).