-
原发性支气管肺癌多数起源于支气管黏膜或腺体, 是常见恶性肿瘤, 且男性患病高于女性, 其致死率较高, 是世界范围内急需解决的公共健康问题。美国每年有大约83万人死于肺癌[1], 约占所有患癌死亡人数的1/3。而我国每年大约有78.7万人被确诊为肺癌, 其发病率可达57.26/10万[2]。大部分肺癌病人确诊时已处于中晚期, 5年生存率为11%[3]。原发性支气管肺癌主要分为小细胞肺癌(SCLC)和非小细胞肺癌(NSCLC)两大类, 其中NSCLC约占85%。目前, 常用的肺癌实验室检测指标包括癌胚抗原(CEA)、神经元特异性烯醇化酶、鳞状上皮细胞癌抗原等。这些肿瘤标志物具有一定的灵敏性和准确性, 使得其在肺癌诊断、分型及预后评价中具有重要的提示意义。近年文献[4]报道, 全身炎症已被证明是恶性肿瘤发生和进展的重要表现。外周血中性粒细胞(NE)减少、血小板(PLT)增多和相关淋巴细胞(LY)减少, 有可能作为术前可获得的预后指标[5-7]。外周血中性粒细胞/淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)亦可能对肺癌的早期诊断具有一定的诊断价值[8-9]。本研究探讨肿瘤标志物联合炎性指标物应用于NSCLC诊断及早期诊断的最佳诊断模型。现作报道。
-
NSCLC组病人WBC、PLT、NE、NLR、PLR、CEA、CYFRA21-1均明显高于对照组(P < 0.01), LY明显低于对照组(P < 0.01)(见表 1)。
分组 n WBC/(×109/L) PLT/(×109/L) NE/(×109/L) LY/(×109/L) NLR PLR CEA/(ng/mL) CYFRA21-1/(ng/mL) 对照组 147 5.95±1.67 210.5±63.5 3.61±1.34 1.83±0.48 2.04±0.81 120.5±44.84 1.68(1.20~2.17) 1.92(1.48~2.37) NSCLC组 84 7.16±2.67 235.4±77.9 4.92±2.40 1.60±0.60 4.01±4.89 176.0±122.00 3.62(2.00~6.96) 3.73(2.33~6.90) t - 4.24 2.64 5.33 3.19 4.78 4.97 1.35* 1.68* P - < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 *示uc值 表 1 2组受试者各指标比较($\bar{x}\pm s$)
-
Ⅲ+Ⅳ期NSCLC病人WBC、NE、CYFRA21-1水平均高于Ⅰ+Ⅱ期(P < 0.05)。鳞癌病人CEA水平低于腺癌(P < 0.05), CYFRA21-1水平高于腺癌(P < 0.05)(见表 2)。
分组 n WBC(×109/L) PLT(×109/L) NE(×109/L) LY(×109/L) NLR PLR CEA/(ng/mL) CYFRA21-1/(ng/mL) Ⅰ+Ⅱ期 47 6.41±2.40 220±77.00 4.27±2.27 1.61±0.54 3.54±5.39 155.6±101.90 3.28(1.98~4.98) 2.96(1.84~4.21) Ⅲ+Ⅳ期 89 7.61±2.77 246±78.00 5.36±2.46 1.57±0.63 4.42±4.87 192.46±135.16 4.27(2.04~8.22) 4.66(2.76~11.02) t - 2.51 1.86 2.52 0.37 0.97 1.64 1.83△ 2.97△ P - < 0.05 >0.05 < 0.05 >0.05 >0.05 >0.05 >0.05 < 0.05 腺癌 92 6.94±2.80 226±65.55 4.74±2.54 1.59±0.56 3.98±5.62 165.68±105.42 4.35(2.02~8.92) 3.07(2.09~5.78) 鳞癌 55 7.61±2.39 251±93.81 5.30±2.14 1.62±0.65 4.09±3.41 195.00±145.39 3.14(1.99~5.28) 5.25(3.19~14.05) t - 1.48 1.90 1.37 0.30 0.13 1.41 1.33△ 0.27△ P - >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 < 0.05 < 0.05 △示uc值 表 2 不同TNM临床分期和不同病理类型NSCLC病人各指标比较($\bar{x}\pm s$)
-
单项指标检测以CYFRA21-1敏感性最高, 而CEA特异性最高, 四项指标联合检测优于单项检测。本研究对CEA、CYFRA21-1、NLR和PLR四项联合检测早期诊断NSCLC价值进行分析, 结果显示其敏感性和特异性分别为83.0%和86.9%(见表 3)。
指标 AUC(95%CI) 敏感性/% 特异性/% 约登指数 CYFRA21-1 0.833 71.4 88.1 0.595 CEA 0.802 61.2 92.9 0.541 NLR 0.737 61.2 82.1 0.434 PLR 0.681 38.8 89.3 0.281 四项联合 0.926 83.7 95.2 0.741 四项联合早期诊断 0.881 83.0 86.9 0.699 表 3 4项血液标志物单项及联合检测的特异性、敏感性及约登指数比较
肿瘤标志物和炎性指标物联合检测对非小细胞肺癌的诊断价值
Diagnostic value of combined detection of tumor markers and inflammatory markers in non-small cell lung cancer
-
摘要:
目的探讨血清肿瘤标志物癌胚抗原(CEA)、细胞角蛋白19片段(CYFRA21-1)和炎性标志物白细胞(WBC)、血小板(PLT)、中性粒细胞(NE)、淋巴细胞(LY)、血小板与淋巴细胞比值(PLR)、中性粒细胞/淋巴细胞比值(NLR)检测在非小细胞肺癌(NSCLC)诊断中的应用价值。 方法选取NSCLC病人147例(NSCLC组),收集同期健康体检者84名资料作为对照组。测定2组WBC、PLT、NE、LY、CEA、CYFRA21-1水平,并计算PLR和NLR,比较2组各指标水平或阳性率差异,以及联合检测对NSCLC的诊断效率。 结果NSCLC组病人WBC、PLT、NE、NLR、PLR、CEA、CYFRA21-1均明显高于对照组(P < 0.01),LY明显低于对照组(P < 0.01)。Ⅲ+Ⅳ期NSCLC病人WBC、NE、CYFRA21-1水平均高于Ⅰ+Ⅱ期(P < 0.05)。鳞癌病人CEA水平低于腺癌(P < 0.05),CYFRA21-1水平高于腺癌(P < 0.05)。CEA、CYFRA21-1、PLR、NLR联合检测诊断NSCLC的敏感性较单项检测敏感性明显增高,其对NSCLC诊断效率为0.926,4项联合检测诊断早期NSCLC的诊断效率为0.881。 结论WBC、PLT、NE、LY、CEA、CYFRA21-1、PLR和NLR水平对于NSCLC有一定的诊断价值,血液WBC、PLT、NE、LY、CEA、CYFRA21-1、PLR和NLR水平联合检测对于NSCLC的诊断较单一指标具有更高的诊断价值。 Abstract:ObjectiveTo investigate the detection of serum tumor markers carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and inflammatory markers white blood cell (WBC), platelet (PLT), neutrophil (NE), lymphocyte (LY), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of non-small cell lung cancer (NSCLC). MethodsA total of 147 NSCLC patients (NSCLC group), and 84 healthy people who had physical examination in the same period (control group) were selected.The levels of WBC, PLT, NE, LY, CEA and CYFRA21-1 were measured in two groups, and PLR, NLR were calculated.The differences of the levels or positive rates of the indicators in two groups were compared, and diagnostic efficacy of combined detection in NSCLC was analyzed. ResultsThe levels of WBC, PLT, NE, NLR, PLR, CEA and CYFRA21-1 in NSCLC group were significantly higher than those in control group, and the LY level was obviously lower than that in control group(P < 0.01).The levels of WBC, NE and CYFRA21-1 of NSCLC patients in stage Ⅲ+Ⅳ were higher than those in stage Ⅰ+Ⅱ(P < 0.05).The level of CEA and CYFRA21-1 in patients with squamous cell carcinoma was lower and higher than that in patients with adenocarcinoma (P < 0.05), respectively.The sensitivity of combined detection of CEA, CYFRA21-1, PLR and NLR in the diagnosis of NSCLC was significantly higher than that of single detection.The diagnostic efficiency of combined detection in NSCLC and early NSCLC was 0.926 and 0.881, respectively. ConclusionsThe levels of WBC, PLT, NE, LY, CEA, CYFRA21-1, PLR and NLR have certain diagnostic values for NSCLC, and the combined detection of WBC, PLT, NE, LY, CEA, CYFRA21-1, PLR and NLR has higher diagnostic value for NSCLC than a single indicator. -
Key words:
- non-small cell lung cancer /
- tumor markers /
- inflammatory markers
-
表 1 2组受试者各指标比较(
)$\bar{x}\pm s$ 分组 n WBC/(×109/L) PLT/(×109/L) NE/(×109/L) LY/(×109/L) NLR PLR CEA/(ng/mL) CYFRA21-1/(ng/mL) 对照组 147 5.95±1.67 210.5±63.5 3.61±1.34 1.83±0.48 2.04±0.81 120.5±44.84 1.68(1.20~2.17) 1.92(1.48~2.37) NSCLC组 84 7.16±2.67 235.4±77.9 4.92±2.40 1.60±0.60 4.01±4.89 176.0±122.00 3.62(2.00~6.96) 3.73(2.33~6.90) t - 4.24 2.64 5.33 3.19 4.78 4.97 1.35* 1.68* P - < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 *示uc值 表 2 不同TNM临床分期和不同病理类型NSCLC病人各指标比较(
)$\bar{x}\pm s$ 分组 n WBC(×109/L) PLT(×109/L) NE(×109/L) LY(×109/L) NLR PLR CEA/(ng/mL) CYFRA21-1/(ng/mL) Ⅰ+Ⅱ期 47 6.41±2.40 220±77.00 4.27±2.27 1.61±0.54 3.54±5.39 155.6±101.90 3.28(1.98~4.98) 2.96(1.84~4.21) Ⅲ+Ⅳ期 89 7.61±2.77 246±78.00 5.36±2.46 1.57±0.63 4.42±4.87 192.46±135.16 4.27(2.04~8.22) 4.66(2.76~11.02) t - 2.51 1.86 2.52 0.37 0.97 1.64 1.83△ 2.97△ P - < 0.05 >0.05 < 0.05 >0.05 >0.05 >0.05 >0.05 < 0.05 腺癌 92 6.94±2.80 226±65.55 4.74±2.54 1.59±0.56 3.98±5.62 165.68±105.42 4.35(2.02~8.92) 3.07(2.09~5.78) 鳞癌 55 7.61±2.39 251±93.81 5.30±2.14 1.62±0.65 4.09±3.41 195.00±145.39 3.14(1.99~5.28) 5.25(3.19~14.05) t - 1.48 1.90 1.37 0.30 0.13 1.41 1.33△ 0.27△ P - >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 < 0.05 < 0.05 △示uc值 表 3 4项血液标志物单项及联合检测的特异性、敏感性及约登指数比较
指标 AUC(95%CI) 敏感性/% 特异性/% 约登指数 CYFRA21-1 0.833 71.4 88.1 0.595 CEA 0.802 61.2 92.9 0.541 NLR 0.737 61.2 82.1 0.434 PLR 0.681 38.8 89.3 0.281 四项联合 0.926 83.7 95.2 0.741 四项联合早期诊断 0.881 83.0 86.9 0.699 -
[1] SIEGEL RL, MILLER KD, JEMAL A.Cancer statistics, 2018[J].Ca A Cancer J Clin, 2018, 60(5):277. [2] 孙可欣, 郑荣寿, 张思维, 等.2015年中国分地区恶性肿瘤发病和死亡分析[J].中国肿瘤, 2019, 28(1):1. [3] CUI L, WEI H.Research status and funding trends of lung cancer biomarkers[J].J Thorac Dis, 2013, 5(5):698. [4] HANAHAN D, WEINBERG RA.Hallmarks of cancer:the next generation[J].Cell, 2011, 144(5):646. [5] GRIVENNIKOV SI, GRETEN FR, KARIN M.Immunity, inflammation, and cancer[J].Cell, 2010, 140:883. [6] MCMILLAN DC.The systemic inflammation-based Glasgow Prognostic Score:a decade of experience in patients with cancer[J].Cancer Treat Rev, 2013, 39(5):534. [7] DAVIES C, PAN H, GODWIN J, et al.Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer:ATLAS, a randomised trial[J].Lancet, 2013, 381:805. [8] STOTZ M, LIEGLATZWANGER B, POSCH F, et al.Blood-based biomarkers are associated with disease recurrence and survival in gastrointestinal stroma tumor patients after surgical resection[J].PLoS One, 2016, 11(7):e0159448. [9] NIKOLIĆIGOR, KUKULJ S, SAMARČIJA M, et al.Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio help identify patients with lung cancer, but do not differentiate between lung cancer subtypes[J].Croatian Med J, 2016, 57(3):287. [10] MANTOVANI A, ALLAVENA P, SICA A, et al.Cancer-related inflammation[J].Nature, 2008, 454(7203):436. [11] ALIUSTAOGLU M, BILICI A, SEKER M, et al.The association of pre-treatment peripheral blood markers with survival in patients with pancreatic cancer[J].Hepatogastroenterol, 2010, 57:640. [12] RAUNGKAEWMANEE S, TANGJITGAMOL S, MANUSIRIVITHAYA S, et al.Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer[J].Gynecol Oncol, 2012, 23(4):265. [13] KWON HC, KIM SH, OH SY, et al.Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer[J].Biomarkers, 2012, 17(3):216. [14] TOMITA M, SHIMIZU T, AYABE T, et al.Preoperative neutrophil to lymphocyte ratio as a prognostic predictor after curative resection for non-small cell lung cancer[J].Anticancer Res, 2011, 31(9):2995. [15] DUTTA S, CRUMLEY AB, FULLARTON GM, et al.Comparison of the prognostic value of tumour and patient related factors in patients undergoing potentially curative resection of gastric cancer.[J].World J Surg, 2011, 35(8):1861. [16] GONG W, YANG S, YANG X, et al.Blood preoperative neutrophil-to-lymphocyte ratio is correlated with TNM stage in patients with papillary thyroid cancer[J].Clinics, 2016, 71(6):311. [17] JIA J, ZHENG X, CHEN Y, et al.Stage-dependent changes of preoperative neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in colorectal cancer[J].Tumor Biol, 2015, 36(12):9319. [18] CELIK O, AKAND M, KESKIN MZ, et al.Preoperative neutrophil-to-lymphocyte ratio (NLR) may be predictive of pathologic stage in patients with Bladder cancer larger than 3 cm[J].Europ Rev Med Pharmacol Sci, 2016, 20(4):652. [19] XU F, XU P, CUI W, et al.Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios may aid in identifying patients with non-small cell lung cancer and predicting Tumor-Node-Metastasis stages[J].Oncol Lett, 2018, 16(1):483. [20] 潘颖, 管世鹤, 杨凯, 等.外周血血小板/淋巴细胞比值在非小细胞肺癌诊断中的价值[J].细胞与分子免疫学杂志, 2016(12):1683. [21] UNAL D, EROGLU C, KURTUL N, et al.Are neutrophil/lymphocyte and platelet/lymphocyte rates in patients with non-small cell lung cancer associated with treatment response and prognosis?[J].Asian Pac J Cancer Prev, 2013, 14(9):5237.