Abstract—

Non-small cell lung cancer (NSCLC) accounts for most cases of lung cancer. Histologically, it is subdivided into two histological subtypes: adenocarcinoma (AC) and squamous cell carcinoma (SCC). The five-year survival rate of patients with stage I NSCLC is two times higher than in patients with stage II and more than five times higher than in stage III−IV lung cancer patients. Currently, there are no informative blood biomarkers to diagnose early stages of NSCLC. The aim of this study was to evaluate complex determination of hyaluronic acid (HA), lymphocyte CXCR2 and granulocyte CXCR1 levels in the blood of patients with AC and SCC. Blood samples from 107 patients with SCC, 90 patients with AC, and 40 healthy people were used in this study. Concentration of HA in blood serum was determined by enzyme linked immunoassay. The level of CXCR2 and CXCR1 was determined by flow cytometry. Diagnostic parameters were determined by constructing mathematical models in the form of regression equations using the method of stepwise inclusion of predictors and subsequent ROC-analysis. Results of the study indicate that MFI CXCR1 in granulocytes, the proportion of lymphocytes expressing CXCR2 and concentration of HA in blood serum in stage I AC and SCC are significantly higher than in healthy people. The level of these indicators significantly increases at stage II of the disease compared to stage I and demonstrates further growth at its later stages. Based on obtained results, regression equations were created. These included: (i) MFI CXCR1 in granulocytes, the proportion of lymphocytes supplied with CXCR2 and the HA serum concentration in to detect stages I−II SCC (diagnostic sensitivity 95.7%, specificity 93.7%, threshold value 0.59) and stages III−IV SCC (diagnostic sensitivity 93.1%, specificity 93.3%, threshold value 0.64); (ii) the proportion of lymphocytes supplied with CXCR2, MFI CXCR1 in granulocytes and CYFRA 21-1 blood level, for detection of I−II stages of AC (sensitivity 91.3%, specificity 94.7%, threshold value 0.61); (iii) the proportion of lymphocytes expressing CXCR2 and CYFRA 21-1 blood level, for detection of AC stages III–IV (sensitivity 94.6%, specificity 91.3%, threshold value 0.15); (IV) the proportion of lymphocytes expressing CXCR2 and serum HA level to differentiate stage II SCC from stage I (sensitivity 94.4%, specificity 87.5%, threshold value 0.44) and II stage AC from stage I (sensitivity 88.5%, specificity 91.2%, threshold value 0.46).

中文翻译：

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测定非小细胞肺癌患者血液中 CXCR1、CXCR2 和透明质酸的诊断效率

摘要——

非小细胞肺癌 (NSCLC) 占肺癌的大多数病例。在组织学上，它被细分为两种组织学亚型：腺癌（AC）和鳞状细胞癌（SCC）。I期NSCLC患者的五年生存率是II期患者的两倍，是III-IV期肺癌患者的五倍以上。目前，没有可用于诊断早期非小细胞肺癌的信息性血液生物标志物。本研究的目的是评估 AC 和 SCC 患者血液中透明质酸 (HA)、淋巴细胞 CXCR2 和粒细胞 CXCR1 水平的复杂测定。本研究使用了来自 107 名 SCC 患者、90 名 AC 患者和 40 名健康人的血液样本。通过酶联免疫测定法测定血清中HA的浓度。通过流式细胞术测定CXCR2和CXCR1的水平。诊断参数通过使用逐步包含预测因子和随后的 ROC 分析的方法以回归方程的形式构建数学模型来确定。研究结果表明，在 I 期 AC 和 SCC 中，粒细胞中的 MFI CXCR1、表达 CXCR2 的淋巴细胞比例和血清中 HA 浓度显着高于健康人。与第一阶段相比，这些指标的水平在疾病的第二阶段显着增加，并在其后期进一步增长。基于获得的结果，创建了回归方程。这些包括：（i）粒细胞中的 MFI CXCR1，提供 CXCR2 的淋巴细胞比例和 HA 血清浓度用于检测 I-II 期 SCC（诊断敏感性 95.7%，特异性 93.7%，阈值 0.59）和 III-IV 期 SCC（诊断敏感性 93.1%，特异性 93.3%，阈值 0.64); (ii) 粒细胞中提供 CXCR2、MFI CXCR1 和 CYFRA 21-1 血液水平的淋巴细胞比例，用于检测 AC 的 I-II 阶段（灵敏度 91.3%，特异性 94.7%，阈值 0.61）；(iii) 表达 CXCR2 和 CYFRA 21-1 血液水平的淋巴细胞比例，用于检测 AC 阶段 III-IV（灵敏度 94.6%，特异性 91.3%，阈值 0.15）；（四）表达CXCR2的淋巴细胞比例和血清HA水平区分II期SCC和I期（敏感性94.4%，特异性87.5%，阈值0。