3rd Department of Internal Medicine, Semmelweis University, Budapest 1125, Hungary.
2nd Department of Surgery, Semmelweis University, Budapest 1125, Hungary.
Cancer Biomark. 2018;23(4):539-547. doi: 10.3233/CBM-181683.
Hsp70 plays important role in the development and progression of cancer. Previously we described the association between serum Hsp70 levels and mortality of colorectal cancer.
In this new prospective study we aimed to confirm and extend our previous findings in a larger cohort of patients, based on a longer follow-up period.
Two hundred and thirty-two patients diagnosed with colorectal cancer were enrolled in the study. Baseline serum Hsp70 level and classical biomarker levels were measured. Patients were treated according to stage of the tumor and follow-up lasted for a median 46.4 months.
We found that serum Hsp70 concentrations increase significantly with stage of the disease (1.79; 2.23 and 3.21 ng/ml in stage I+II, III and IV respectively, p= 0.012 and 0.002, Mann-Whitney test) and with other known biomarkers of the disease. We managed to confirm our previous findings that high baseline serum Hsp70 level (> 1.64 ng/ml) predicted poor 5-year survival (risk of death HR: 1.94 CI: 1.294-2.909; univariate; HR: 2.418 CI: 1.373-4.258; multivariate Cox regression analysis) in the whole patient population and also in subgroups of stage IV and stage III disease. The strongest association was observed in women under age of 70 (HR: 8.12, CI: 2.02-35.84; p= 0.004; multivariate Cox regression). The power of this colorectal cancer prognostic model could be amplified by combining Hsp70 levels and inflammatory markers. Patients with high Hsp70, CRP and high baseline WBC or platelet count had 5-times higher risk of death (HR: 5.07 CI: 2.74-9.39, p< 0.0001; and HR: 4.98 CI: 3.08-8.06, p< 0.0001 respectively).
These results confirm and validate our previous findings that serum Hsp70 is a useful biomarker of colorectal cancer.
Hsp70 在癌症的发展和进展中起着重要作用。我们之前描述了血清 Hsp70 水平与结直肠癌死亡率之间的关系。
在更大的患者队列中，基于更长的随访时间，我们旨在确认并扩展之前的发现。
纳入 232 名诊断为结直肠癌的患者。测量基线血清 Hsp70 水平和经典生物标志物水平。根据肿瘤分期对患者进行治疗，随访中位数为 46.4 个月。
我们发现，血清 Hsp70 浓度随着疾病的分期显著增加（I+II 期、III 期和 IV 期分别为 1.79、2.23 和 3.21ng/ml，p=0.012 和 0.002，Mann-Whitney 检验），并与疾病的其他已知生物标志物相关。我们成功地证实了之前的发现，即基线时血清 Hsp70 水平较高（>1.64ng/ml）预示着较差的 5 年生存率（死亡风险 HR：1.94，95%CI：1.294-2.909；单因素 HR：2.418，95%CI：1.373-4.258；多因素 Cox 回归分析），在整个患者人群中，以及在 IV 期和 III 期疾病的亚组中。在年龄小于 70 岁的女性中观察到最强的关联（HR：8.12，95%CI：2.02-35.84；p=0.004；多因素 Cox 回归）。通过结合 Hsp70 水平和炎症标志物，可以放大该结直肠癌预后模型的效能。Hsp70、CRP 和高基线白细胞或血小板计数较高的患者死亡风险增加 5 倍（HR：5.07，95%CI：2.74-9.39，p<0.0001；和 HR：4.98，95%CI：3.08-8.06，p<0.0001）。
这些结果证实并验证了我们之前的发现，即血清 Hsp70 是结直肠癌的一种有用的生物标志物。
