血浆HA与外周血M2型单核细胞/M1型单核细胞比值联合检测在乳腺癌中的临床应用价值
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摘要
目的探讨血浆透明质酸(HA)与外周血M2型单核细胞/M1型单核细胞比值(简称M2/M1比值)联合检测在乳腺癌中的临床应用价值。方法选取98例乳腺癌患者(乳腺癌组)、37例乳腺良性疾病患者(乳腺良性疾病组)和41名体检健康者(正常对照组)。采用化学发光法检测血浆HA和糖类抗原(CA)15-3水平;采用流式细胞术检测外周血M1型(CD14+CD163-CD86+)和M2型(CD14+CD163+CD204+)单核细胞的表达,并计算M2/M1比值。各项指标之间的相关性分析采用Spearman相关分析。采用受试者工作特征(ROC)曲线分析各项指标的诊断效能。结果乳腺癌组血浆HA、CA15-3水平及M2型单核细胞比例、M2/M1比值均明显高于乳腺良性疾病组及正常对照组(P<0.05),而乳腺良性疾病组与正常对照组之间差异均无统计学意义(P>0.05)。HA与M2/M1比值、M2型单核细胞比例、M1型单核细胞比例均相关(rs值分别为0.401、0.393、-0.189,P<0.05)。M2/M1比值诊断乳腺癌的曲线下面积(AUC)、敏感性和特异性均高于其他指标,且HA与M2/M1比值联合检测可提高对乳腺癌的诊断效能。血浆HA与乳腺癌组织学分化情况有关(P<0.05),M2/M1比值与乳腺癌TNM分期、淋巴结转移、组织学分化情况及雌激素受体(ER)均有关(P<0.05),CA15-3与乳腺癌临床病理特征均无关(P>0.05)。结论 HA与M2/M1比值联合检测对辅助诊断乳腺癌具有一定的临床价值。
Objective To investigate the role of the combined determination of plasma hyaluronan(HA)and the ratio of M2 monocyte/M1 monocyte(M2/M1 ratio) in breast cancer. Methods A total of 98 patients with breast cancer(breast cancer group),37 patients with breast benign diseases(breast benign disease group) and41 healthy subjects(healthy control group) were enrolled. Plasma HA and carbohydrate antigen(CA)15-3 levels were determined by chemiluminescence. Flow cytometry was used to assess the expression of M1(CD14+CD163-CD86+) and M2(CD14+CD163+CD204+) monocytes,and M2/M1 ratio was calculated. Correlation analysis was performed using Spearman correlation analysis. Receiver operating characteristic(ROC) curve was used to analyze the diagnostic ef?ciency of each marker. Results Plasma HA and CA15-3 levels,the proportion of M2 monocyte and M2/M1 ratio were higher in breast cancer group than those in breast benign disease and healthy control groups(P<0.05),and there was no statistical significance between breast benign disease and healthy control groups(P>0.05). There were correlations of HA with M2/M1 ratio and the proportions of M2 monocyte and M1 monocyte(rs=0.401,0.393 and-0.189,P<0.05). The area under ROC curve(AUC),sensitivity and specificity of M2/M1 ratio for the diagnosis of breast cancer were higher than those of the other markers,and the combined determination of HA and M2/M1 ratio could improve the diagnostic efficiency of breast cancer. Plasma HA was correlated with the histological differentiation of breast cancer(P<0.05),and M2/M1 ratio was correlated with tumor-node-metastasis(TNM) stage,histological differentiation,lymph node metastasis and estrogen receptor(ER)(P<0.05). However,there was no relationship between CA15-3 and clinicopathological characteristics(P>0.05). Conclusions The combined determination of HA and M2/M1 ratio plays a role in the auxiliary diagnosis of breast cancer.
Objective To investigate the role of the combined determination of plasma hyaluronan(HA)and the ratio of M2 monocyte/M1 monocyte(M2/M1 ratio) in breast cancer. Methods A total of 98 patients with breast cancer(breast cancer group),37 patients with breast benign diseases(breast benign disease group) and41 healthy subjects(healthy control group) were enrolled. Plasma HA and carbohydrate antigen(CA)15-3 levels were determined by chemiluminescence. Flow cytometry was used to assess the expression of M1(CD14+CD163-CD86+) and M2(CD14+CD163+CD204+) monocytes,and M2/M1 ratio was calculated. Correlation analysis was performed using Spearman correlation analysis. Receiver operating characteristic(ROC) curve was used to analyze the diagnostic ef?ciency of each marker. Results Plasma HA and CA15-3 levels,the proportion of M2 monocyte and M2/M1 ratio were higher in breast cancer group than those in breast benign disease and healthy control groups(P<0.05),and there was no statistical significance between breast benign disease and healthy control groups(P>0.05). There were correlations of HA with M2/M1 ratio and the proportions of M2 monocyte and M1 monocyte(rs=0.401,0.393 and-0.189,P<0.05). The area under ROC curve(AUC),sensitivity and specificity of M2/M1 ratio for the diagnosis of breast cancer were higher than those of the other markers,and the combined determination of HA and M2/M1 ratio could improve the diagnostic efficiency of breast cancer. Plasma HA was correlated with the histological differentiation of breast cancer(P<0.05),and M2/M1 ratio was correlated with tumor-node-metastasis(TNM) stage,histological differentiation,lymph node metastasis and estrogen receptor(ER)(P<0.05). However,there was no relationship between CA15-3 and clinicopathological characteristics(P>0.05). Conclusions The combined determination of HA and M2/M1 ratio plays a role in the auxiliary diagnosis of breast cancer.
引文
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[2]SOUSA S,BRION R,LINTUNEN M,et al.Human breast cancer cells educate macrophages toward the M2activation status[J].Breast Cancer Res,2015,17:101.
[3]R O U S S O S E T,B A L S A M O M,A L F O R D S K,et al.Mena invasive(MenaINV)promotes multicellular streaming motility and transendothelial migration in a mouse model of breast cancer[J].J Cell Sci,2011,124(Pt13):2120-2131.
[4]ADAMS D L,MARTIN S S,ALPAUGH R K,et al.Circulating giant macrophages as a potential biomarker of solid tumors[J].Proc Natl Acad Sci U S A,2014,111(9):3514-3519.
[5]SICA A,SCHIOPPA T,MANTOVANI A,et al.Tumourassociated macrophages are a distinct M2 polarised population promoting tumour progression:potential targets of anti-cancer therapy[J].Eur J Cancer,2006,42(6):717-727.
[6]ZHANG B,CAO M,HE Y,et al.Increased circulating M2-like monocytes in patients with breast cancer[J].Tumour Biol,2017,39(6):1010428317711571.
[7]WU M,CAO M,HE Y,et al.A novel role of low molecular weight hyaluronan in breast cancer metastasis[J].FASEB J,2015,29(4):1290-1298.
[8]TIAINEN S,TUMELIUS R,RILLA K,et al.High numbers of macrophages,especially M2-like(CD163-positive),correlate with hyaluronan accumulation and poor outcome in breast cancer[J].Histopathology,2015,66(6):873-883.
[9]MANTOVANI A,SOZZANI S,LOCATI M,et al.Macrophage polarization:tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes[J].Trends Immunol,2002,23(11):549-555.
[10]MAEDA R,ISHII G,NERI S,et al.Circulating CD14+CD204+cells predict postoperative recurrence in nonsmall-cell lung cancer patients[J].J Thorac Oncol,2014,9(2):179-188.
[11]LI C,LUO X,LIN Y,et al.A higher frequency of CD14+CD169+monocytes/macrophages in patients with colorectal cancer[J].PLoS One,2015,10(10):e0141817.
[12]OSTUNI R,KRATOCHVILL F,MURRAY P J,et al.Macrophages and cancer:from mechanisms to therapeutic implications[J].Trends Immunol,2015,36(4):229-239.
[13]C L AW S O N G A,M AT T E R S G L,X I N P,e t a l.Macrophage-tumor cell fusions from peripheral blood of melanoma patients[J].PLoS One,2015,10(8):e0134320.
[14]KUANG D M,WU Y,CHEN N,et al.Tumor-derived hyaluronan induces formation of immunosuppressive macrophages through transient early activation of monocytes[J].Blood,2007,110(2):587-595.