Importance of circulating adipocytokines in multiple myeloma: a systematic review and meta-analysis based on case-control studies

Abstract

Background Adipocytes and their products, adipocytokines, play important roles in the generation and development of multiple myeloma (MM). Studies have demonstrated some adipocytokines to be associated with MM, although those results are controversial. Therefore, we conducted a meta-analysis to verify the association of adipocytokines with MM. Methods We performed a systematic retrieval of literature published prior to 26 October 2021. Standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated to evaluate pooled effects. Subgroup analysis and meta-regression analysis were conducted to detect sources of heterogeneity. Sensitivity analysis was performed to evaluate the stability of the study. Publication bias was assessed by funnel plots and Egger’s linear regression test. Results Ten eligible studies with 1269 MM patients and 2158 controls were included. The pooled analyses indicated that circulating leptin levels of MM patients were significantly higher than control levels (SMD= 0.87, 95%CI: 0.33 to 1.41), while the circulating adiponectin levels in MM patients were significantly lower than controls with a pooled SMD of -0.49 (95%CI: -0.78 to -0.20). The difference of circulating resistin levels were not significant between MM patients and controls (SMD= -0.08, 95%CI: -0.55 to 0.39). Subgroup analysis and meta-regression analysis found that sample size, age, and sex were possible sources of heterogeneity. Sensitivity analysis demonstrated our pooled results to be stable. Conclusion Decreased circulating adiponectin and increased leptin levels were associated with the occurrence and development of MM. Adiponectin and leptin may be potential biomarkers and therapeutic targets for MM.

Association of lipid levels, adipokines and multiple myeloma: a two-sample multivariate Mendelian randomization study

“…A study including 73 MM patients and 73 controls showed that low circulating resistin concentrations were associated with MM risk 8 . However, a meta-analysis of seven studies including 367 MM patients and 524 controls 53 showed no signi cant difference in circulating resistin levels between the two groups. The role of resistin in MM is complex, with some studies suggesting that it is a protective adipokine, and Pang et al 58 found that resistin abrogates chemotherapy-induced apoptosis in myeloma cells by inhibiting chemotherapy-induced cysteine asparaginase cleavage, thereby enhancing multidrug resistance in MM.…”

“…Leptin has direct and indirect biological effects on the regulation of cancer proliferation, metastasis, angiogenesis and chemoresistance 51 . Existing studies on the relationship between leptin and MM remain contradictory, and a study that included 14 patients with MM and 25 healthy controls showed that serum leptin levels were higher in the MM group (than in healthy controls) 52 Liu et al 53 conducted a meta-analysis in 2021 showing higher leptin concentrations in MM patients than in controls. However, Hofmann et al 54 10 In an in vitro experiment, leptin was shown to induce modi cations in gene expression, thereby enhancing MM cell growth and viability.…”

Obesity as a risk factor for multiple myeloma: insight on the role of adipokines

“…A meta-analysis was conducted by Liu et al in 2021 to analyze seven studies with 406 MM patients and 530 controls. They demonstrated higher leptin concentrations in MM patients than in controls (SMD = 0.87, CI = 0.33–1.41, z = 3.14, p = 0.002) [ 50 ]. Alexandrakis et al examine examined leptin levels in the serum of 62 MM patients, according to the established Durie and Salmon criteria, they divided patients into stage I ( n = 13), stage II ( n = 22), stage III ( n = 27).…”

“…Interestingly Reseland et al showed that the level of resistin had no significant difference between the newly diagnosed MM patients and controls [ 49 ]. Pooled analysis of 367 MM patients and 524 controls showed no significant difference in circulating resistin levels (SMD = −0.08, 95%CI = −0.55 to 0.39, p = 0.73) [ 50 ].…”

Calorie restriction has no effect on bone marrow tumour burden in a Vk*MYC transplant model of multiple myeloma

“…Weight loss and a reduction of white adipose tissue (WAT) are characteristic of CR. The reduction in WAT leads to reduced circulating levels of WAT-secreted factors such as the pro-inflammatory adipokine leptin, high levels of which has been associated with occurrence and development of MM 26 .…”