Background Epidemiological studies have shown that patients with type 2 diabetes mellitus (T2DM) are at a higher risk of secondary tumors. However, no consensus has been made about whether T2DM can increase the risk of multiple myeloma (MM). Methods We searched the databases of PubMed, Cochrane Library and EMBASE and cross-checked the bibliography. Data quality was assessed using the Newcastle-Ottawa scale (NOS). Heterogeneity was calculated as the odds ratio (OR) using a random-effects model. Data were analyzed using Stata version 12.0 software. Results A total of 13 articles were selected into this meta-analysis. Initially, we found that diabetic patients had a higher risk of myeloma than non-diabetic patients (OR =1.60, 95% CI: 1.13–2.26, I 2 =98%, P=0.000). But the data in these articles were highly heterogeneous (I 2 >75%). Therefore, eight of the included articles showed a moderate heterogeneity (I 2 =71.6%). We used Galbraith heterogeneity map to analyze the causes of heterogeneity. Two articles with high heterogeneity were excluded. Then, we found the heterogeneity of the left six articles was reduced from moderate to mild (I 2 =45.9%, P=0.100). The final results of this meta-analysis showed that T2DM was not a risk factor for increased incidence of MM (OR =1.05, 95% CI: 0.83–1.33, I 2 =45.9%, P=0.100). Also, the subgroup analysis (case-control studies vs. cohort studies) showed no statistical difference (OR =1.19, 95% CI: 0.76–1.85, I 2 =1%, P=0.364; OR =1.00, 95% CI: 0.75–1.33, I 2 =71.2%, P=0.031; respectively). Conclusions T2DM is not a risk factor for the increased incidence of MM, a finding that should be validated with more strictly designed randomized controlled trials (RCTs).

This study aimed to investigate whether annexin A7 (ANXA7) could promote the cell cycle, proliferation and cell adhesion-mediated drug resistance (CAM-DR) of multiple myeloma (MM) cells by up-regulating cell division cycle 5-like (CDC5L). As a result, ANXA7 expression was increased in the serum of MM patients and the expression of ANXA7 and CDC5L was also increased in MM cell lines. ANXA7 overexpression promoted the proliferation and cycle of U266 and RPMI8226 cells. The expression of proliferation cell nuclear antigen (PCNA), KI67, cyclin dependent kinase 1 (CDK1) and cyclinB1 in transfected cells was consistent with the changes of proliferation and cell cycle. In co-culture system of BMSC cells and MM cells, expression of CD44, ICAM1 and VCAM1 in MM cells was increased, which was further increased by ANXA7 overexpression. Bortezomib could increase the apoptosis of U266 and RPMI8226 cells. In co-culture system of BMSC cells and MM cells, the promotion effects of bortezomib on apoptosis of MM cells was decreased, which was further suppressed by ANXA7 overexpression. The above effects exerted by ANXA7 overexpression could be reversed by ANXA7 interference. Moreover, ANXA7 was proved to be combined with CDC5L. CDC5L interference could inhibit the promotion effects of ANXA7 overexpression on proliferation and cell cycle and inhibition effects of ANXA7 overexpression on apoptosis of MM cells treated with bortezomib in co-culture system. In conclusion, ANXA7 could promote the cell cycle, proliferation and CAM-DR of MM cells by upregulating CDC5L.