术前血清透明质酸水平与乳腺癌患者预后的相关性分析

Correlation analysis of the prognostic value of serum hyaluronic acid for breast cancer patients

目的探讨术前血清透明质酸(HA)含量水平与乳腺癌患者预后的相关性。方法从历史性队列中选择2004年1月至2014年11月在浙江大学医学院附属邵逸夫医院肿瘤科进行手术治疗的98例乳腺癌患者,年龄为(52.5±9.4)岁。检测患者术前血清HA含量,根据其中位数53.7μg/L,将患者分成高低两组,各49例。并采用χ²检验分析血清HA含量高低与患者一般临床资料的相关性,同时采用Kaplan‑Meier法绘制生存曲线,Log‑rank进行检验以及多因素Cox回归模型分析HA含量和患者生存期的相关性。结果高HA水平的患者在绝经和未绝经患者中比例分别为55.7%和40.5%;在孕激素受体(PR)阳性和阴性患者中分别为54.1%和43.2%;在雌激素受体(ER)阳性和阴性患者中分别为45.7%和60.7%;在Ki‑67阳性和阴性患者中分别为55.6%和43.2%;在肿瘤大小TⅠ,TⅡ,TⅢ和TⅣ期患者中分别为50.0%,41.7%,72.7%和1/1;在淋巴结转移和未转移患者中分别为45.7%和53.8%。HA水平高低与乳腺癌患者的绝经状态、PR、ER、Ki‑67表达、肿瘤大小分期、淋巴结转移无显著相关性(χ²值分别为2.128,1.086,1.800,1.485,4.273,0.656,P>0.05)。高HA水平的患者在年龄小于等于52岁患者中占30.9%,大于52岁中占74.4%(χ²=18.274,P=0.000);在TNM早期患者中占43.4%,晚期中占72.7%(χ²=5.861,P=0.015);在未远端转移患者中占45.2%,远端转移中占78.6%(χ²=5.333,P=0.023);在Her‑2阴性患者中占38.1%,阳性中占58.9%(χ²=4.167,P=0.041);而且高HA水平的患者生存期中位数70个月要小于低HA水平组的83个月(χ²=6.799,P=0.007)。因此,高HA含量与患者年龄大,较晚的肿瘤分期,较高的远端转移风险,Her‑2的阳性表达和较短的生存期相关。多因素Cox回归模型分析提示,血清HA高水平可能是患者生存的危险因素,HR(95%CI)值为9.98(1.16~85.88),P值0.036。结论术前血清HA的高水平与较差的乳腺癌患者预后有一定的相关性。

Objective To explore the correlation between preoperative serum hyaluronic acid(HA)level and prognosis of breast cancer patients.Methods The 98 patients with breast cancer who underwent surgical treatment in the Oncology Department of Sir Run Run Shaw Hospital,Zhejiang University School of Medicine from January 2004 to November 2014 in a historical cohort were included,aged(52.5±9.4)years.The preoperative serum HA contents of the patients were detected.According to the median of 53.7μg/L,the patients were divided into high and low groups with 49 patients in each group.Theχ2 test was used to analyze the correlation between the serum HA content and the general clinical data of the patients,and the Kaplan‑Meier method,Log‑rank test and multivariate Cox regression model wereusedto analyze the correlation between HA content and patients′survival.Results The percentages of patients with high HA levels in menopause and non‑menopause patientswere 55.7%and 40.5%,respectively;in progesterone receptor(PR)positive and negative patients were 54.1%and 43.2%,respectively;in estrogen receptor(ER)positive and negative patients were 45.7%and 60.7%,respectively;in Ki‑67 positive and negative patients were 55.6%and 43.2%,respectively;in the tumor size stage TⅠ,TⅡ,TⅢ,and TⅣpatients were 50.0%,41.7%,72.7%,and 1/1,respectively;in lymph node metastasis and non‑metastasispatients were 45.7%and 53.8%,respectively.There was no significant correlation between the level of HA and the menopausal status,the expressions of PR,ER and Ki‑67,tumor size,and lymph node metastasis in breast cancer patients(χ²=2.128,1.086,1.800,1.485,4.273,0.656,P>0.05).Patients with high HA levels accounted for 30.9%of patients aged 52 years or less and 74.4%of patients older than 52 years(χ²=18.274,P=0.000);43.4%of patients with early TNM and 72.7%of patients with advanced TNM(χ²=5.861,P=0.015);45.2%of patients without distant metastasis and 78.6%of patients with distant metastasis(χ²=5.333,P=0.023);38.1%of Her‑2 negative patients and 58.9%of Her‑2 positive patients(χ²=4.167,P=0.041);and the median survival of patients with high HA levels was 70 months,which was shorter than 83 months for patients with low HA levels(χ²=6.799,P=0.007).Therefore,ahigh HA content predicts an older age,a later tumor stage,higher risk of distant metastasis,positive expression of Her‑2 and shorter survival.Multivariate Cox regression model analysis suggested that high levels of serum HA may be a risk factor for patients′survival,with HR(95%CI)value of 9.98(1.16-85.88)and P value of 0.036.Conclusion The high level of preoperative serum HA has a certain correlation with the poor prognosis of breast cancer patients.