Abstract—

Non-small cell lung cancer (NSCLC) dominates in the morbidity of lung cancer. In stage I, only 60–70% patients overcome the 5-year survival barrier, and in stage II 5-year survival rate is declining to 35–40%. The reason for such a high mortality is relapse of the disease. The main histological forms of NSCLC are adenocarcinoma (AС) and squamous cell carcinoma (SCC). They differ in course, protocols and effectiveness of treatment. Comparative survival data for AC and SCC are controversial, and reliable biomarkers for determining the risk of tumor progression still have not been found. In order to determine the risk of disease progression we have investigated the possibility of using laboratory parameters characterizing the level of some blood proteins involved in carcinogenesis in patients with early stages of AС and SCC. We retrospectively analyzed the duration of relapse-free period after surgical treatment for one year in 1250 patients (816 with stages I and II AC, G1-3 and 434 with early stages of SCC, G1-3). In 81 AC patients and 36 SCC patients (stages I−II, G1-3) we determined the level of CYFRA 21-1 and SCC, TPA, chemokines CXCL5, CXCL8, pyruvate kinase M2, HIF-1α, hyaluronic acid and receptors CXCR1, CXCR2, CD44v6. Using the Kaplan−Meier graphical analysis, groups of low (stage I G1-2 + stage II G1) and high (stage I G3 + stage II G2-3) risk of tumor progression were identified. The one-year survival rate of AС patients was higher than in SCC patients. AС patients with high risk of tumor recurrence had higher levels of CYFRA 21-1, the mean intensity of fluorescence (MFI) of CXCR1 receptor in granulocytes, and the relative content of CXCR2 receptor in lymphocytes than patients with low risk. In the case of rapid disease progression in SCC patients, the relative content of CXCR2 receptor in lymphocytes, the proportion of monocytes supplied with CD44v6 receptor, and SCC level were higher than in patients with slow progression. Regression equations, including combinations of the above parameters (threshold value for AC—0.512, for SCC—0.409, sensitivity—91.9% and 90.0%, specificity—90.0% and 87.5%, respectively), allow to predict the probability of tumor recurrence.

中文翻译：

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基于实验室参数确定早期腺癌和鳞状细胞肺癌患者的肿瘤进展风险

摘要——

非小细胞肺癌（NSCLC）在肺癌发病率中占主导地位。在 I 期，只有 60-70% 的患者克服了 5 年生存障碍，而在 II 期，5 年生存率正在下降到 35-40%。如此高的死亡率的原因是疾病的复发。NSCLC的主要组织学形式是腺癌（AС）和鳞状细胞癌（SCC）。它们在疗程、方案和治疗效果方面有所不同。AC 和 SCC 的比较生存数据存在争议，并且尚未发现用于确定肿瘤进展风险的可靠生物标志物。为了确定疾病进展的风险，我们研究了使用实验室参数来表征早期 AС 和 SCC 患者致癌作用中某些血液蛋白水平的可能性。我们回顾性分析了 1250 例患者（816 例 I 和 II 期 AC，G1-3 和 434 例 SCC 早期，G1-3）手术治疗后 1 年的无复发期持续时间。在 81 名 AC 患者和 36 名 SCC 患者（I-II 期，G1-3）中，我们确定了 CYFRA 21-1 和 SCC、TPA、趋化因子 CXCL5、CXCL8、丙酮酸激酶 M2、HIF-1α、透明质酸和受体 CXCR1 的水平，CXCR2，CD44v6。使用 Kaplan-Meier 图形分析，确定了肿瘤进展的低（I G1-2 期 + II G1 期）和高（I G3 期 + II G2-3 期）风险组。AС 患者的一年生存率高于 SCC 患者。具有高肿瘤复发风险的 AС 患者具有较高水平的 CYFRA 21-1，粒细胞中 CXCR1 受体的平均荧光强度 (MFI)，且淋巴细胞中CXCR2受体的相对含量低于低危患者。在SCC患者疾病进展较快的情况下，淋巴细胞中CXCR2受体的相对含量、提供CD44v6受体的单核细胞比例和SCC水平均高于进展缓慢的患者。回归方程，包括上述参数的组合（AC 的阈值-0.512，SCC 的阈值-0.409，敏感性分别为 91.9% 和 90.0%，特异性分别为 90.0% 和 87.5%），可以预测肿瘤复发的概率。