Department of Hematology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Hematology. 2022 Dec;27(1):596-602. doi: 10.1080/16078454.2022.2072062.
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.
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.
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).
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.
长链非编码 RNA ANGPTL1-3（lnc-ANGPTL1-3）先前被观察到通过靶向多发性骨髓瘤（MM）中的 microRNA-30a（miR-30a）诱导硼替佐米耐药。因此，本研究旨在进一步探讨 lnc-ANGPTL1-3 与 miR-30a 之间的关系及其与硼替佐米治疗的 MM 患者疾病特征和预后的联系。
59 例 MM 患者接受硼替佐米为基础的治疗方案，连续纳入 30 例健康供者。采集 MM 患者（治疗前）和健康供者的骨髓样本；然后通过 RT-qPCR 检测血浆细胞中的 lnc-ANGPTL1-3 和 miR-30a。然后评估 MM 患者的治疗反应、无进展生存期（PFS）和总生存期（OS）。
与健康供者相比，MM 患者的 lnc-ANGPTL1-3 上调而 miR-30a 下调（均<0.001），然后在 MM 患者中发现 lnc-ANGPTL1-3 与 miR-30a 之间存在负相关（<0.001），而在健康供者中则没有（=0.188）。在 MM 患者中，lnc-ANGPTL1-3 与增加的 t（4;14）（=0.033）、Del（17p）（=0.018）、ISS 分期（=0.020）、R-ISS 分期（=0.025）相关，但与 t（14;16）（=0.255）或 Durie-Salmon 分期（=0.186）无关；而 miR-30a 仅与 t（14;16）（=0.025）和 R-ISS 分期（=0.006）的降低有关。此外，lnc-ANGPTL1-3 预测较低的完全缓解率（CR）（=0.034）、较差的 PFS（=0.016）和 OS（=0.041），但与客观缓解率（ORR）（=0.128）无关。然而，miR-30a 预测更高的 CR（=0.013）、延长的 PFS（=0.014）和 OS（=0.045），但与 ORR（=0.407）无关。
lnc-ANGPTL1-3 与 miR-30a 呈负相关，与接受硼替佐米为基础的治疗方案的 MM 患者的关键细胞遗传学特征、ISS/R-ISS 分期和预后相关。
