血清热休克蛋白家族A成员9蛋白作为多发性骨髓瘤患者硼替佐米耐药和预后不良的生物标志物

IF 2.2 4区 医学 Q3 ONCOLOGY
Lin Chen, Shuang Gao, Li Lin, Su Liu, Jing Ma, Zhiying Zhang, Qian Li
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引用次数: 0

摘要

多发性骨髓瘤(MM)的硼替佐米耐药是限制长期疗效的重大临床挑战。目前,缺乏可靠的生物标志物来预测硼替佐米耐药性。先前的研究报道了几种蛋白通过靶向泛素-蛋白酶体途径调节博尔替佐米耐药,包括热休克蛋白家族A成员9 (HSPA9)、dickkopf Wnt信号通路抑制剂1 (DKK1)、蛋白酶体26S亚基非atp酶14 (PSMD14)和tripartite motif containing 21 (TRIM21)。在我们的研究中,我们旨在分析这些蛋白在MM患者中的表达,并评估它们作为硼替佐米耐药生物标志物的潜力。我们的研究招募了46名新诊断的MM患者(38名硼替佐米敏感患者和8名硼替佐米耐药患者)和52名健康对照者,并收集了患者在初始治疗前的血清样本。ELISA法检测各组血清HSPA9、DKK1、PSMD14、TRIM21蛋白水平。通过受试者工作特征曲线结合曲线下面积(AUC)评价HSPA9蛋白对硼替佐米耐药的诊断能力。采用卡方检验检验HSPA9蛋白与临床病理特征的相关性,采用Kaplan-Meier法和Cox回归分析评估预后价值。与健康对照组相比,MM患者血清中HSPA9和DKK1表达升高,TRIM21蛋白表达降低。两组间PSMD14蛋白表达差异无统计学意义。值得注意的是,与硼替佐米敏感患者相比,只有HSPA9蛋白在硼替佐米耐药患者中被发现上调,而在其他蛋白中没有发现差异。此外,区分MM患者与健康对照的血清HSPA9的AUC为0.906[95%可信区间(CI): 0.843-0.968]。血清HSPA9表达能有效区分硼替佐米耐药MM患者和硼替佐米敏感MM患者,AUC为0.845 (95% CI: 0.734 ~ 0.957)。此外,血清HSPA9表达升高与国际分期系统晚期、β2-MG升高、免疫球蛋白异常和硼替佐米耐药呈正相关。较高的血清HSPA9与较短的总生存率相关,并独立预测预后不良。我们的研究表明,血清HSPA9蛋白升高可作为MM患者硼替佐米耐药和预后不良的潜在生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Serum heat shock protein family A member 9 protein as a biomarker for bortezomib resistance and poor prognosis in patients with multiple myeloma.

Bortezomib resistance in multiple myeloma (MM) is a significant clinical challenge that limits the long-term effectiveness. Currently, there is a lack of reliable biomarkers to predict bortezomib resistance. Previous studies reported that several proteins regulate bortezomib resistance through targeting ubiquitin-proteasome pathways, including heat shock protein family A member 9 (HSPA9), dickkopf Wnt signaling pathway inhibitor 1 (DKK1), proteasome 26S subunit non-ATPase 14 (PSMD14), and tripartite motif containing 21 (TRIM21). In our study, we aimed to analyze the expression of these proteins in MM patients and evaluate their potential as biomarkers for bortezomib resistance. Our study enrolled 46 newly diagnosed MM patients (38 bortezomib-sensitive and eight bortezomib-resistant patients) and 52 healthy controls, and serum samples were collected from the patients before initial treatments. The levels of HSPA9, DKK1, PSMD14, and TRIM21 proteins in serum samples were measured using ELISA. The diagnostic power of HSPA9 protein for bortezomib resistance was evaluated through receiver operating characteristic curves combined with the area under curve (AUC). The correlation between HSPA9 protein and clinicopathological features was examined using the chi-square test, and Kaplan-Meier method and Cox regression analysis were applied to assess prognostic value. Compared with healthy controls, increased HSPA9 and DKK1, but decreased TRIM21 protein expression, were observed in serum samples from MM patients. There was no statistical difference in PSMD14 protein expression between the two groups. Notably, compared with bortezomib-sensitive patients, only HSPA9 protein was found to be upregulated in bortezomib-resistant patients, whereas no differences were found in the other proteins. Furthermore, the AUC of serum HSPA9 for differentiating MM patients from healthy controls was 0.906 [95% confidence interval (CI): 0.843-0.968]. And serum HSPA9 expression could effectively differentiate bortezomib-resistant MM patients from bortezomib-sensitive MM patients, with an AUC of 0.845 (95% CI: 0.734-0.957). In addition, elevated serum HSPA9 expression positively correlated with advanced International Staging System stage, increased β2-MG, abnormal immunoglobulin, and bortezomib resistance. Higher serum HSPA9 was linked to shorter overall survival rate and independently predicted poor prognosis. Our study demonstrated that elevated serum HSPA9 protein serves as a potential biomarker for bortezomib resistance and poor prognosis in MM patients.

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来源期刊
Anti-Cancer Drugs
Anti-Cancer Drugs 医学-药学
CiteScore
3.80
自引率
0.00%
发文量
244
审稿时长
3 months
期刊介绍: Anti-Cancer Drugs reports both clinical and experimental results related to anti-cancer drugs, and welcomes contributions on anti-cancer drug design, drug delivery, pharmacology, hormonal and biological modalities and chemotherapy evaluation. An internationally refereed journal devoted to the fast publication of innovative investigations on therapeutic agents against cancer, Anti-Cancer Drugs aims to stimulate and report research on both toxic and non-toxic anti-cancer agents. Consequently, the scope on the journal will cover both conventional cytotoxic chemotherapy and hormonal or biological response modalities such as interleukins and immunotherapy. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool.
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