Alu hypermethylation and high oxidative stress in patients with musculoskeletal tumors

作者：Woraruthai Thamonwan; Charoenlap Chris; Hongsaprabhas Chindanai; Mutirangura Apiwat; Honsaweki Sittisak^*

来源：PeerJ, 2018, 6: e5492.

DOI：10.7717/peerj.5492

• Alu methylation
• 8-OHdG
• Blood leukocytes
• Oxidative stress
• Musculoskeletal tumors

Background. Alu is one of the non-autonomous element retrotransposons, constituting nearly 11% of the human DNA. Methylation changes of the Alu element can cause genomic instability, a hallmark of cancer development, ultimately leading to the development of cancer. Epigenetic factors may induce the aberrant methylation of Alu and also oxidative stress. However, current knowledge of Alu methylation and oxidative stress is limited. There are few studies that have evaluated Alu methylation and oxidative stress on musculoskeletal tumor progression. Therefore, the present study evaluated the status of Alu methylation in musculoskeletal (MS) tumor, adjacent tissues, and blood leukocytes from MS tumor subjects, as well as unaffected participants. Moreover, we also investigated the oxidative stress status in MS tumor subjects and the control participants and determined the correlation between Alu methylation in MS tumors and that in blood leukocytes.
Methods. Musculoskeletal tumors from musculoskeletal tumor patients (n = 40) were compared to adjacent tissues (n = 40). The blood leukocytes from musculoskeletal tumor patients were compared to the blood leukocytes from controls (n = 107). Alu methylation status was analyzed using quantitative combined bisulfite restriction analysis (COBRA). In addition, 8-hydroxy 2'-deoxyguanosine (8-OHdG) values were determined using enzyme-linked immunosorbent assay.
Results. Alu methylation values in MS tumors were statistically significantly higher than those in adjacent tissues (P = 0.035). Similarly, Alu methylation statuses in the blood leukocytes of MS tumor subjects were statistically greater than those of control participants (P < 0.001). Moreover, there was a positive association between Alu methylation levels in MS tumors and blood leukocytes (r = 0 .7 65 , P < 0.001). In addition, the highest tertile was significantly associated with the risk of MS tumors (OR = 14.17, 95% CI [5.08-39.51]; P < 0.001). The 8-OHdG values in MS tumors were statistically higher than in adjacent tissues (P < 0.001) and circulating 8-OHdG levels were substantially greater in MS tumor subjects than in the control participants (P < 0.001).
Discussion. These findings suggest that Alu methylation in blood leukocytes and plasma 8-OHdG might represent non-invasive biomarkers to help diagnose MS tumors. Therefore, Alu hypermethylation and high oxidative stress might be involved in the pathogenesis of the musculoskeletal tumors.

• 出版日期2018-8-16