外周血生物标志物在前列腺癌鉴别诊断中的作用及对恶性程度评判价值
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摘要
目的探讨外周血生物标志物或联合检测对前列腺癌鉴别诊断的作用,并分析标志物在前列癌不同恶性程度间的差异性。方法回顾性分析2015年1月至2016年12月于中国医学科学院肿瘤医院就诊的126例前列腺癌(prostate cancer,PCa)患者和34例前列腺增生(benign prostatic hyperplasia,BPH)患者的临床资料,应用Logistic回归和受试者工作特征曲线(ROC)分析前列腺疾病患者的外周血生物标志物或多指标联合分析对前列腺癌鉴别诊断的价值。按照前列腺癌恶性程度分组对各指标进行差异分析。结果绘制各指标用于鉴别前列腺癌和前列腺增生的ROC结果显示总前列腺特异抗原(tPSA)和游离/总前列腺特异抗原(fPSA/tPSA)及血小板/淋巴细胞(PLR)的曲线下面积(AUC)最大。Logistic回归和ROC曲线分析结果提示:tPSA和fPSA/tPSA联合分析诊断效能最佳(AUC为0.76),联合PLR不能提高tPSA和fPSA/tPSA对前列腺癌鉴别诊断效能。前列腺癌不同恶性程度组间差异性分析结果显示:在126例前列癌患者中,外周血PLR和中性粒/淋巴细胞(NLR)在不同tPSA及临床分期间存在组间差异(P<0.05),乳酸脱氢酶(LDH)在前列腺癌不同恶性程度分组间未见明显差异。结论外周血生物标志物tPSA和fPSA/tPSA联合分析对前列腺癌鉴别诊断价值最大,外周血PLR和NLR可辅助tPSA、Gleason评分和临床分期评估前列腺癌的恶性程度,对前列腺癌恶性程度评判具有一定的提示作用。
Objective This study aimed to evaluate the difference of the application of peripheral blood biomarkers in the differential diagnosis of prostate cancer. Methods Clinical data of 126 patients with prostate cancer(PCa) and 34 patients with benign prostatic hyperplasia(BPH) in National Cancer Hospital between January 2015 and December 2016 was retrospectively collected. Logistic regression and ROC curves were used to explore the diagnostic value of markers in peripheral blood. The differences of markers were analyzed according to the malignant degree of prostate cancer. Results The results of ROC curve to distinguish BPH and PCa showed showed that the AUC of tPSA, fPSA/tPSA and PLR were the largest. The results of Logistic regression and ROC curve analysis of combined markers showed that the diagnostic efficiency of tPSA and fPSA/tPSA combined analysis was the best with AUC =0. 76. Comparisons among different degrees of malignant groups in 126 patients with PCa,PLR and NLR in peripheral blood showed significant differences among different tPSA and clinical classifications(P <0. 05). There was no significant difference in LDH among different degree of malignant groups. Conclusion Our results suggested that combined-analysis of tPSA and fPSA/tPSA had the best diagnostic efficiency for BPH and PCa. PLR and NLR in peripheral blood can assist tPSA, Gleason scoring and clinical staging to assess the malignancy of prostate cancer and have potenialpositive effects on evaluating malignancy.
Objective This study aimed to evaluate the difference of the application of peripheral blood biomarkers in the differential diagnosis of prostate cancer. Methods Clinical data of 126 patients with prostate cancer(PCa) and 34 patients with benign prostatic hyperplasia(BPH) in National Cancer Hospital between January 2015 and December 2016 was retrospectively collected. Logistic regression and ROC curves were used to explore the diagnostic value of markers in peripheral blood. The differences of markers were analyzed according to the malignant degree of prostate cancer. Results The results of ROC curve to distinguish BPH and PCa showed showed that the AUC of tPSA, fPSA/tPSA and PLR were the largest. The results of Logistic regression and ROC curve analysis of combined markers showed that the diagnostic efficiency of tPSA and fPSA/tPSA combined analysis was the best with AUC =0. 76. Comparisons among different degrees of malignant groups in 126 patients with PCa,PLR and NLR in peripheral blood showed significant differences among different tPSA and clinical classifications(P <0. 05). There was no significant difference in LDH among different degree of malignant groups. Conclusion Our results suggested that combined-analysis of tPSA and fPSA/tPSA had the best diagnostic efficiency for BPH and PCa. PLR and NLR in peripheral blood can assist tPSA, Gleason scoring and clinical staging to assess the malignancy of prostate cancer and have potenialpositive effects on evaluating malignancy.
引文
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[10]叶波,张珂,宋晓玉.血清tPSA及fPSA/tPSA比值在前列腺癌诊断中的价值[J].检验医学与临床,2012,9(6):651-652.
[11]北京协和医院医疗诊疗常规泌尿外科分册[M].第2版.人民卫生出版社,2012:152.
[12]MCDONALD B,SPICER J,GIANNAIS B,et al.Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms[J].Int J Cancer,2009,125(6):1298-1305.
[13]KUSUMANTO Y H,DAM W A,HOSPER G A,et al.Platelets and granulocytes,in particular the neutrophils,form important compartments for circulating vascular endothelial growth factor[J].Angiogenesis,2003,6(4):283-287.
[14]SUZUKI K,KACHALA S S,KADOTA K,et al.Prognostic immune markers in non-small cell lung cancer[J].Clin Cancer Res,2011,17(16):5247-5256.
[15]LI F,HU H,GU S,et al.Platelet to lymphocyte ratio plays an important role in prostate cancer's diagnosis and prognosis[J].Int J Clin Exp Med,2015,8(7):11746-11751.
[16]WANG Y,XU F,PAN J,et al.Platelet to lymphocyte ratio as an independent prognostic indicator for prostate cancer patients receiving androgen deprivation therapy[J].BMC Cancer,2016,16:329.doi:10.1186/s12885-016-2363-5.
[17]WULANINGSIH W,HOLMBERG L,GARMO H,et al.Serum lactate dehydrogenase and survival following cancer diagnosis[J].Br J Cancer,2015,113(9):1389-1396.
[2]CHEN W,ZHENG R,BAADE P D,et al.Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.
[3]LI J,ZHU S,TONG J,et al.Suppression of lactate dehydrogenase A compromises tumor progression by downregulation of the Warburg effect in glioblastoma[J].Neuroreport,2016,27(2):110-115.
[4]CHEN CY,FENG Y,CHEN JY,et al.Identification of a potent inhibitor targeting human lactate dehydrogenase A and its metabolic modulation for cancer cell line[J].Bioorg Med Chem Lett,2016,26(1):72-75.
[5]VANDER HEIDEN M G,CANTLEY L C,THOMPSON C B.Understanding the warburg effect:The metabolic requirements of cell proliferation[J].Science,2009,324(5930):1029-1033.
[6]LIU D,HUANG Y,LI L,et al.High neutrophil-to-lymphocyte ratios confer poor prognoses in patients with small cell lung cancer[J].BMC Cancer,2017,17(1):882.doi:10.1186/s12885-017-3893-1.
[7]YUS L,XUL T,QI Q,et al.Serum lactate dehydrogenase predicts prognosis and correlates with systemic inflammatory response in patients with advanced pancreatic cancer after gemcitabine-based chemotherapy[J].Sci Rep,2017,7:45194.doi:10.1038/srep45194.
[8]WANG Q,YANG Y,ZHANG Y P,et al.Prognostic value of carbohydrate tumor markers and inflammation-based markers in metastatic or recurrent gastric cancer[J].Med Oncol,2014,31(12):289.doi:10.1007/s12032-014-0289-9.
[9]D'AMICOA V,WHITTINGTONR,MALKOWICZS B,et al.Biochemical outcome after radical prostatectomy,external beam radiation therapy,or interstitial radiation therapy for clinically localized prostate cancer[J].JAMA,1998,280(11):969-974.
[10]叶波,张珂,宋晓玉.血清tPSA及fPSA/tPSA比值在前列腺癌诊断中的价值[J].检验医学与临床,2012,9(6):651-652.
[11]北京协和医院医疗诊疗常规泌尿外科分册[M].第2版.人民卫生出版社,2012:152.
[12]MCDONALD B,SPICER J,GIANNAIS B,et al.Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms[J].Int J Cancer,2009,125(6):1298-1305.
[13]KUSUMANTO Y H,DAM W A,HOSPER G A,et al.Platelets and granulocytes,in particular the neutrophils,form important compartments for circulating vascular endothelial growth factor[J].Angiogenesis,2003,6(4):283-287.
[14]SUZUKI K,KACHALA S S,KADOTA K,et al.Prognostic immune markers in non-small cell lung cancer[J].Clin Cancer Res,2011,17(16):5247-5256.
[15]LI F,HU H,GU S,et al.Platelet to lymphocyte ratio plays an important role in prostate cancer's diagnosis and prognosis[J].Int J Clin Exp Med,2015,8(7):11746-11751.
[16]WANG Y,XU F,PAN J,et al.Platelet to lymphocyte ratio as an independent prognostic indicator for prostate cancer patients receiving androgen deprivation therapy[J].BMC Cancer,2016,16:329.doi:10.1186/s12885-016-2363-5.
[17]WULANINGSIH W,HOLMBERG L,GARMO H,et al.Serum lactate dehydrogenase and survival following cancer diagnosis[J].Br J Cancer,2015,113(9):1389-1396.