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血浆L-多巴/酪氨酸比值、S100B、黑色素抑制活性(MIA)和乳酸脱氢酶(LDH)联合检测在黑色素瘤中的临床价值

Clinical value of combined determination of plasma L-DOPA/tyrosine ratio, S100B, MIA and LDH in melanoma.

作者信息

Garnier Jean-Pierre, Letellier Sabine, Cassinat Bruno, Lebbé Celeste, Kerob Delphine, Baccard Michel, Morel Patrice, Basset-Seguin Nicole, Dubertret Louis, Bousquet Bernard, Stoitchkov Konstantin, Le Bricon Thierry

机构信息

Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris V, France.

出版信息

Eur J Cancer. 2007 Mar;43(4):816-21. doi: 10.1016/j.ejca.2006.11.022. Epub 2007 Feb 5.

Abstract

AIM OF THE STUDY

L-DOPA/tyrosine ratio (an index of tyrosinase activity), melanoma antigens S100B and MIA, lactate deshydrogenase (LDH) and their combinations were evaluated for clinical value as tumour markers in melanoma.

METHODS

Blood samples were obtained in 170 melanoma patients (stage I-II: n=57, III: n=54, IV: n=59) at inclusion and in a sub-group of 82 subjects during follow-up for up to 4 years. Laboratory analyses were performed by HPLC (L-DOPA, L-tyrosine), immunoassays (S100B, MIA) and colourimetry (LDH).

RESULTS

All markers, except LDH, were elevated in stage IV versus other stages. S100B and MIA highly correlated, especially in stage IV (r(s): 0.849, p<0.001). The combination of L-DOPA/tyrosine ratio with S100B displayed the highest sensitivity/specificity (73/70%) to confirm stage III-IV or stage IV alone (69/75%) (ROC optimised cut-off). Only the L-DOPA/tyrosine ratio significantly increased (+36% over 5 months, p=0.001) during progression from stage I-III to higher stages. S100B, MIA and LDH, but not the L-DOPA/tyrosine ratio, responded to progression towards death in stage IV. All markers exhibited a prognostic value in deceased patients (n=44); S100B and MIA were the best predictors of survival time by Cox proportional-hazards regression.

CONCLUSION

The combination of plasma L-DOPA/tyrosine ratio and S100B appears an attractive approach for the biological follow-up of melanoma patients.

摘要

研究目的

评估左旋多巴/酪氨酸比值(酪氨酸酶活性指标)、黑色素瘤抗原S100B和MIA、乳酸脱氢酶(LDH)及其组合作为黑色素瘤肿瘤标志物的临床价值。

方法

纳入170例黑色素瘤患者(I-II期:n = 57,III期:n = 54,IV期:n = 59),采集其入组时的血样,并在82名受试者的亚组中进行长达4年的随访。通过高效液相色谱法(左旋多巴、L-酪氨酸)、免疫测定法(S100B、MIA)和比色法(LDH)进行实验室分析。

结果

除LDH外,所有标志物在IV期均高于其他阶段。S100B和MIA高度相关,尤其是在IV期(斯皮尔曼相关系数:0.849,p<0.001)。左旋多巴/酪氨酸比值与S100B的组合在确认III-IV期或单独IV期时显示出最高的敏感性/特异性(73/70%)(优化的ROC临界值)。从I-III期进展到更高阶段时,只有左旋多巴/酪氨酸比值显著升高(5个月内升高36%,p = 0.001)。在IV期向死亡进展过程中,S100B、MIA和LDH有反应,但左旋多巴/酪氨酸比值无反应。所有标志物在死亡患者(n = 44)中均具有预后价值;通过Cox比例风险回归分析,S100B和MIA是生存时间的最佳预测指标。

结论

血浆左旋多巴/酪氨酸比值与S100B的组合似乎是黑色素瘤患者生物学随访的一种有吸引力的方法。

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