Improvement of differential diagnosis of lung cancer by use of multiple protein tumor marker combinations.

Q3 Biochemistry, Genetics and Molecular Biology Tumor Biology Pub Date : 2024-01-01 DOI:10.3233/TUB-230021

Inga Trulson, Frank Klawonn, Joachim von Pawel, Stefan Holdenrieder

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Abstract

Background: Differential diagnosis of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) in hospitalized patients is crucial for appropriate treatment choice.

Objective: To investigate the relevance of serum tumor markers (STMs) and their combinations for the differentiation of NSCLC and SCLC subtypes.

Methods: Between 2000 and 2003, 10 established STMs were assessed retrospectively in 311 patients with NSCLC, 128 with SCLC prior systemic first-line therapy and 51 controls with benign lung diseases (BLD), by automatized electrochemiluminescence immunoassay technology. Receiver operating characteristic (ROC) curves and logistic regression analyses were used to evaluate the diagnostic efficacy of both individual and multiple STMs with corresponding sensitivities at 90% specificity. Standards for Reporting of Diagnostic Accuracy (STARD guidelines) were followed.

Results: CYFRA 21-1 (cytokeratin-19 fragment), CEA (carcinoembryonic antigen) and NSE (neuron specific enolase) were significantly higher in all lung cancers vs BLD, reaching AUCs of 0.81 (95% CI 0.76-0.87), 0.78 (0.73-0.84), and 0.88 (0.84-0.93), respectively. By the three marker combination, the discrimination between benign and all malignant cases was improved resulting in an AUC of 0.93 (95% CI 0.90-0.96). In NSCLC vs. BLD, CYFRA 21-1, CEA and NSE were best discriminative STMs, with AUCs of 0.86 (95% CI 0.81-0.91), 0.80 (0.74-0.85), and 0.85 (0.79-0.91). The three marker combination also improved the AUC: 0.92; 95% CI 0.89-0.96). In SCLC vs. BLD, ProGRP (pro-gastrin-releasing peptide) and NSE were best discriminative STMs, with AUCs of 0.89 (95% CI 0.84-0.94) and 0.96 (0.93-0.98), respectively, and slightly improved AUC of 0.97 (95% CI 0.95-0.99) when in combination. Finally, discrimination between SCLC and NSCLC was possible by ProGRP (AUC 0.86; 95% CI 0.81-0.91), NSE (AUC 0.83; 0.78-0.88) and CYFRA 21-1 (AUC 0.69; 0.64-0.75) and by the combination of the 3 STMs (AUC 0.93; 0.91-0.96), with a sensitivity of 88% at 90% specificity.

Conclusions: The results confirm the power of STM combinations for the differential diagnosis of lung cancer from benign lesions and between histological lung cancer subtypes.

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利用多种蛋白质肿瘤标记物组合改进肺癌的鉴别诊断。

背景：对住院患者进行非小细胞肺癌（NSCLC）和小细胞肺癌（SCLC）的鉴别诊断对于选择适当的治疗方法至关重要：目的：研究血清肿瘤标志物（STMs）及其组合对区分非小细胞肺癌和小细胞肺癌亚型的相关性：方法：在 2000 年至 2003 年期间，采用自动电化学发光免疫测定技术对 311 例 NSCLC 患者、128 例 SCLC 患者和 51 例良性肺部疾病（BLD）对照者进行了回顾性评估。利用接收者操作特征曲线（ROC）和逻辑回归分析评估了单个和多个 STM 的诊断效果，以及在 90% 特异性条件下的相应灵敏度。结果：结果：CYFRA 21-1（细胞角蛋白-19片段）、CEA（癌胚抗原）和NSE（神经元特异性烯醇化酶）在所有肺癌与BLD中均显著升高，AUC分别为0.81（95% CI 0.76-0.87）、0.78（0.73-0.84）和0.88（0.84-0.93）。通过三种标记物的组合，良性病例和所有恶性病例之间的区分度得到了提高，AUC 为 0.93（95% CI 0.90-0.96）。在 NSCLC vs. BLD 中，CYFRA 21-1、CEA 和 NSE 是最佳的鉴别 STM，其 AUC 分别为 0.86（95% CI 0.81-0.91）、0.80（0.74-0.85）和 0.85（0.79-0.91）。三种标记物组合也提高了 AUC：0.92；95% CI 0.89-0.96）。在 SCLC vs. BLD 中，ProGRP（促胃泌素释放肽）和 NSE 是最佳的鉴别 STM，AUC 分别为 0.89（95% CI 0.84-0.94）和 0.96（0.93-0.98），联合使用时 AUC 略有提高，为 0.97（95% CI 0.95-0.99）。最后，ProGRP（AUC 0.86；95% CI 0.81-0.91）、NSE（AUC 0.83；0.78-0.88）和CYFRA 21-1（AUC 0.69；0.64-0.75）以及3种STMs的组合（AUC 0.93；0.91-0.96）可以区分SCLC和NSCLC，敏感性为88%，特异性为90%：结果证实了 STM 组合在肺癌与良性病变的鉴别诊断以及肺癌组织学亚型之间的鉴别诊断中的作用。

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来源期刊

Tumor Biology 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Tumor Biology is a peer reviewed, international journal providing an open access forum for experimental and clinical cancer research. Tumor Biology covers all aspects of tumor markers, molecular biomarkers, tumor targeting, and mechanisms of tumor development and progression. Specific topics of interest include, but are not limited to: Pathway analyses, Non-coding RNAs, Circulating tumor cells, Liquid biopsies, Exosomes, Epigenetics, Cancer stem cells, Tumor immunology and immunotherapy, Tumor microenvironment, Targeted therapies, Therapy resistance Cancer genetics, Cancer risk screening. Studies in other areas of basic, clinical and translational cancer research are also considered in order to promote connections and discoveries across different disciplines. The journal publishes original articles, reviews, commentaries and guidelines on tumor marker use. All submissions are subject to rigorous peer review and are selected on the basis of whether the research is sound and deserves publication. Tumor Biology is the Official Journal of the International Society of Oncology and BioMarkers (ISOBM).