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

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