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热休克蛋白 90α 在恶性黑色素瘤中的诊断和预后价值。

Diagnostic and prognostic value of heat shock protein 90α in malignant melanoma.

机构信息

Department of Oncology.

Department of Psychiatry, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.

出版信息

Melanoma Res. 2021 Apr 1;31(2):152-161. doi: 10.1097/CMR.0000000000000716.

Abstract

Malignant melanoma is one of the most common tumours of the skin. Heat shock protein 90α (HSP90α) has been applied in the auxiliary diagnosis of various malignancies, as a tumour marker. This study aims to evaluate diagnostic, therapeutic efficacy and prognostic value of plasma HSP90α levels in malignant melanoma. In this study, higher plasma HSP90α levels and abnormal rates were found in malignant melanoma patients than in healthy controls (92.63 vs. 51.84 ng/mL; P  < 0.001 and 68.30 vs. 8.30%; P < 0.001). Plasma HSP90α levels were higher with Breslow thickness >4 mm, a high Clark level (IV + V), abnormal serum lactate dehydrogenase (LDH), distant metastases occurrence and Ki-67≥30% (P < 0.05). The area under the curves (AUCs) of HSP90α was greater than LDH in the training (0.847 vs. 0.677) and validation (0.867 vs. 0.672) cohort. Meanwhile, the sensitivity (76.70%) and negative predictive values (78.80%) of HSP90α were higher. Plasma HSP90α levels were significantly reduced in objective response (81.05 vs. 37.26 ng/mL; P = 0.012) and disease control patients (84.16 vs. 47.05 ng/mL; P = 0.002) post-treatment. Patients with normal HSP90α levels had slightly longer progression-free survival (PFS) than those with abnormal levels (8.0 vs. 3.5 months; P = 0.096). Unfortunately, the trend was not statistically significant. In multivariable analysis, immunotherapy was an independent prognostic factor for PFS. Nevertheless, patients with normal HSP90α levels who received chemotherapy(±targeted therapy) without immunotherapy had significantly longer PFS than patients with abnormal levels (6.0 vs. 2.0 months; P = 0.008). Therefore, HSP90α can be used for auxiliary diagnosis and predict the responses to therapy in malignant melanoma patients.

摘要

恶性黑色素瘤是最常见的皮肤肿瘤之一。热休克蛋白 90α(HSP90α)已被应用于各种恶性肿瘤的辅助诊断,作为肿瘤标志物。本研究旨在评估血浆 HSP90α 水平在恶性黑色素瘤中的诊断、治疗疗效和预后价值。

在这项研究中,与健康对照组相比,恶性黑色素瘤患者的血浆 HSP90α 水平和异常率更高(92.63 比 51.84ng/ml;P<0.001 和 68.30 比 8.30%;P<0.001)。Breslow 厚度>4mm、高 Clark 水平(IV+V)、异常血清乳酸脱氢酶(LDH)、远处转移发生和 Ki-67≥30%时,血浆 HSP90α 水平更高(P<0.05)。在训练(0.847 比 0.677)和验证(0.867 比 0.672)队列中,HSP90α 的曲线下面积(AUC)均大于 LDH。同时,HSP90α 的敏感性(76.70%)和阴性预测值(78.80%)更高。

治疗后,客观缓解(81.05 比 37.26ng/ml;P=0.012)和疾病控制患者(84.16 比 47.05ng/ml;P=0.002)的血浆 HSP90α 水平显著降低。HSP90α 水平正常的患者无进展生存期(PFS)略长于水平异常的患者(8.0 比 3.5 个月;P=0.096)。遗憾的是,这种趋势没有统计学意义。多变量分析显示,免疫治疗是 PFS 的独立预后因素。然而,接受化疗(±靶向治疗)而未接受免疫治疗的 HSP90α 水平正常的患者的 PFS 明显长于水平异常的患者(6.0 比 2.0 个月;P=0.008)。

因此,HSP90α 可用于恶性黑色素瘤患者的辅助诊断,并预测治疗反应。

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