血清NSE、ProGRP和LDH在小细胞肺癌诊断治疗中的作用

Utility of NSE, Pro GRP and LDH in Diagnosis and Treatment in Patients with Small Cell Lung Cancer

背景与目的小细胞肺癌(small cell lung cancer,SCLC)是一种生长迅速、具有神经内分泌特性的肿瘤。血清神经元特异性烯醇化酶(neuron specific enolase,NSE)、胃泌素释放肽前体(pro-gastrin-releasing peptide,Pro GRP)和乳酸脱氢酶(lactic dehydrogenase,LDH)已在SCLC的诊断和治疗中起到一定的辅助作用,本研究旨在通过治疗前后SCLC患者NSE、Pro GRP和LDH的变化探讨标志物在肿瘤分期、疗效评价及预测复发方面的价值。方法纳入中国医学科学院肿瘤医院的SCLC初治病例,回顾性分析其临床数据,包括临床特征、治疗前及2周期化疗后的血清NSE、Pro GRP及LDH,疗效及无进展生存期。结果治疗前,广泛期(extensive disease,ED)患者NSE、Pro GRP及LDH均高于局限期(limited disease,LD)(P<0.005);LD患者的NSE水平随淋巴结分期的升高而明显增加(P=0.010);有体重下降的患者NSE及LDH均高于无体重下降者(P=0.032,P=0.014)。化疗2周期后,有效患者的NSE及Pro GRP下降程度明显高于疗效为稳定或无效的患者(P=0.015,P=0.002)。LD组化疗周期数>4个及治疗后Pro GRP下降明显的患者较化疗周期数≤4个及Pro GRP下降不明显的患者复发风险低;而远处转移数目≤2个、疗前LDH正常及治疗后Pro GRP的明显下降,提示ED患者的近期复发风险低。此外,肿瘤复发类型(敏感复发、耐药复发、难治复发)与化疗后Pro GRP下降程度呈负相关(P=0.044)。多因素分析结果提示治疗周期数是LD组SCLC近期复发的独立影响因素,远处转移数目及治疗后Pro GRP的下降程度是ED组SCLC近期复发的独立影响因素。结论血清肿瘤标志物升高的程度与肿瘤负荷相关,Pro GRP在治疗后的下降程度可能预测疗效及复发风险。

Background and objective Small cell lung cancer （SCLC） is a rapidly growing tumor with character-istic of neuroendocrine cellular function. Neuron speciifc enolase （NSE）, pro-gastrin-releasing peptide （ProGRP） and lactic dehydrogenase （LDH） are valuable in diagnosis and treatment of SCLC. By analyzing the variation of NSE, ProGRP and LDH before and atfer treatment, the aim of this study is to investigate the effcacy of tumor markers in diagnostic staging, therapeu-tic evaluation and prediction of disease relapsing.Methods Patients with SCLC who receiving the ifrst line chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled and retrospectively analyzed. Clinical characteristic （includes NSE, ProGRP and LDH level before and atfer 2 cycles chemotherapy）, effcacy evaluation, progression-free survival （PFS） were analyzed.Results Before treatment, Serum NSE, ProGRP and LDH in patients with extensive disease （ED） were signiifcantly higher than those with limited disease （LD）（allP〈0.005）; NSE level increased obviously accompanied by increase of lymph nodes stage in LD group （P=0.010）; Patients with weight reduction when diagnosis had higher NSE and LDH than those without loss of weight （P=0.032,P=0.014）. Atfer 2 cycles chemotherapy, decrease of NSE and ProGRP in effective group was higher than which in stable and ineffective groups （P=0.015,P=0.002）. hTe relapse risk was lower in patients who accepted〉4 cycles chemotherapy and with obvious decrease of ProGRP than those who accepted ≤4 cycles chemotherapy and with less obvious decrease of ProGRP in LD group; ED patients with no more than 2 distant metastasis, normal LDH level before treat-ment and obvious decrease of ProGRP atfer chemotherapy had lower short term relapse risk. In addition, the types of relapse （sensitive relapse, drug resistance relapse and refractory relapse） were negatively correlated with decrease of ProGRP （P=0.044）. By multivariate analysis, numbers of chemotherapy cycle was independent prognostic factor for PFS in LD SCLC; numbers of distant metastasis and decrease of ProGRP were independent prognostic factors for PFS in ED SCLC.Conclusion Increase level of serum tumor markers is related to tumor burden. Decrease level of ProGRP atfer treatment may prognose effcacy and relapse risk.