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硒蛋白 P 在决定宫颈癌患者同步放化疗敏感性中的作用:基于代谢组学的分析。

The role of selenoprotein P in the determining the sensitivity of cervical cancer patients to concurrent chemoradiotherapy: A metabonomics-based analysis.

机构信息

Institute of Keshan Disease, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin 150081, China.

Department of Public Health, Jining Medical University, Jining 272029, China.

出版信息

J Trace Elem Med Biol. 2022 Sep;73:127041. doi: 10.1016/j.jtemb.2022.127041. Epub 2022 Jul 18.

Abstract

BACKGROUND

The effect of selenoprotein P (SELENOP) levels on the sensitivity of cervical cancer patients to concurrent chemoradiotherapy (CCRT) has not been reported. In this study, the effects of the variations in plasma SELENOP levels on the sensitivity of cervical cancer patients to CCRT were investigated using metabonomics.

METHODS

Two patient groups were evaluated, i.e., the case group: 11 patients with intermediate to advanced primary squamous cervical cancer, who developed resistance against CCRT, and the sensitivity group: 11 patients who did not develop resistance were matched in a 1:1 ratio (controls). Blood samples were collected before and after CCRT, and the plasma SELENOP levels were measured by ELISA. The different metabolites present in the plasma were analyzed by UPLC-MS-MS.

RESULTS

SELENOP levels exhibited a significant reduction in both the resistant and sensitive groups after CCRT (F = 50.705, P < 0.001), and interaction effects between sensitivity and pre-and post-treatment on SELENOP levels were observed (F = 7.414, P = 0.013). Further, a more significant reduction in the SELENOP levels was observed in the CCRT-resistant group (mean reduction, 0.028 µg/mL; P < 0.001) than in the sensitive group (mean reduction, 0.013 µg/mL; P = 0.006). Four metabolic biomarkers, i.e., C18, C19, C20 sphingomyelin, and phosphatidylcholine 20:2/22:6, were shown to be differentially expressed between the resistant and sensitive groups pre-and post-treatment. C20 sphingomyelin levels exhibited a significant correlation with SELENOP levels (r = -0.326, P = 0.031).

CONCLUSION

The levels of plasma SELENOP in the CCRT-resistant group decreased significantly, suggesting that SELENOP might affect the sensitivity by modulating lipid synthesis and metabolism.

摘要

背景

目前尚无研究报道硒蛋白 P(SELENOP)水平对宫颈癌患者同步放化疗(CCRT)敏感性的影响。本研究采用代谢组学方法探讨了血浆 SELENOP 水平的变化对宫颈癌患者 CCRT 敏感性的影响。

方法

评估了两组患者,即耐药组:11 例中晚期原发性宫颈鳞癌患者,对 CCRT 产生耐药性;以及敏感组:11 例未产生耐药性的患者,按 1:1 比例配对(对照组)。在 CCRT 前后采集血样,通过 ELISA 法测定血浆 SELENOP 水平。采用 UPLC-MS-MS 分析血浆中存在的不同代谢物。

结果

CCRT 后耐药组和敏感组的 SELENOP 水平均显著降低(F=50.705,P<0.001),且在治疗前后 SELENOP 水平的敏感性与治疗之间存在交互作用(F=7.414,P=0.013)。此外,耐药组 SELENOP 水平的降低更为显著(平均降低 0.028µg/mL;P<0.001),而敏感组的降低则相对较少(平均降低 0.013µg/mL;P=0.006)。治疗前后,耐药组和敏感组之间有 4 种代谢生物标志物,即 C18、C19、C20 神经鞘磷脂和磷脂酰胆碱 20:2/22:6,差异有统计学意义。C20 神经鞘磷脂水平与 SELENOP 水平呈显著负相关(r=-0.326,P=0.031)。

结论

CCRT 耐药组的血浆 SELENOP 水平显著降低,提示 SELENOP 可能通过调节脂质合成和代谢影响敏感性。

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