College of Biomedical Engineering, Taiyuan University of Technology, Taiyuan, 030024, Shanxi, China.
Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, China.
Biomed Res Int. 2021 Oct 19;2021:9623571. doi: 10.1155/2021/9623571. eCollection 2021.
This study is aimed at teasing out the correlation of plasma D-dimer (D-D) levels to age, metastasis, TNM stage (tumor-node-metastasis classification), and treatment in non-small-cell lung cancer (NSCLC) patients of different ages, to facilitate early diagnosis of hypercoagulable state, choose appropriate treatment, and use appropriate anticoagulants. Hence, thrombosis and complications caused by excessive anticoagulants can be prevented; thrombus or disseminated intravascular coagulation (DIC) and other complications in elderly patients with NSCLC can be reduced or avoided. By monitoring the level of plasma D-D in patients with NSCLC, recurrence and metastasis can be predicted in the early stage and the TNM stage can be evaluated.
A total of 670 patients with NSCLC were selected in Shanxi Bethune Hospital from March 2014 to October 2020 as the experimental group, and 950 healthy people were selected from the physical examination center of the same hospital as the control group. The data of patients with NSCLC diagnosed for the first time without any treatment were collected and grouped based on metastasis, TNM stage, treatment, and pathological type, and the correlation with plasma D-D level was analyzed. Plasma D-D levels were measured by immunoturbidimetry on an ACL TOP 700 Automatic Coagulation Analyzer. The patients were further divided into two groups according to different treatment methods, and the differences in plasma D-D levels between patients receiving chemotherapy and those receiving targeted therapy in different treatment cycles were analyzed. The correlation between D-D levels and age in healthy controls was analyzed. The difference in D-D levels between NSCLC patients and healthy controls of the same age was analyzed.
All data of both the experimental group and the control group were normally distributed. The average age of the experimental group was 61.31 ± 6.23 (range: 36-92) years. The average age of the control group was 61.14 ± 11.12 (range: 35-85) years. There was no significant difference in gender between the experimental group and the control group ( > 0.05). The plasma D-D level of NSCLC patients was significantly higher than that of the healthy controls ( < 0.05). No significant difference in plasma D-D level was found between NSCLC patients of different genders, and the finding was similar between healthy controls of different genders ( > 0.05). Significant difference in the D-D level was found between the groups of 30-59 years and 60-69 years ( < 0.05), between groups of 60-69 years and 70-79 years ( < 0.05), and between 70-79 years and ≥80 years ( < 0.05). The plasma D-D level of patients ≤ 79 years old increased with age, but it decreased in those over 80 years old. According to Pearson correlation analysis, there was a positive correlation between the D-D level and the age of NSCLC patients under 79 years old ( < 0.05). The differences in D-D levels between the four age groups were statistically significant ( < 0.05), showing an upward trend of the D-D level in healthy controls with the increase of age. There were statistically significant differences in D-D levels between NSCLC patients and healthy controls of the matching age group ( < 0.05), suggesting that NSCLC patients had significantly higher D-D levels than healthy people of the same age group. The differences in D-D levels between NSCLC patients without metastasis, NSCLC patients with metastasis, and healthy people were statistically significant ( < 0.05). The patients with metastasis had the highest D-D level, and healthy people had the lowest D-D level. The difference in plasma D-D levels between patients of different TNM stages was statistically significant ( < 0.05). Patients with an advanced TNM stage tended to have higher D-D levels. The TNM stage and D-D level of NSCLC patients changed significantly before and after treatment. An earlier stage was related to a more obvious change in D-D levels after treatment with a statistically significant difference ( < 0.05). A more advanced stage was associated with a smaller change in the D-D level after treatment, with no statistically significant difference ( > 0.05). The plasma D-D levels before and after four cycles of chemotherapy or targeted therapy were higher than those of the healthy control group, and the differences were statistically significant ( < 0.05). The D-D level of patients after chemotherapy was significantly lower than that before chemotherapy ( < 0.05), but there was no significant difference before and after targeted therapy ( > 0.05). The D-D level after the first cycle of chemotherapy was higher than that before chemotherapy. The level of D-D after the third and fourth cycles was significantly lower than that before chemotherapy ( < 0.05). No significant difference was found between the D-D level before treatment and that after four cycles of chemotherapy ( > 0.05).
It is suggested that coagulation test indexes should be included to evaluate the treatment regimen for NSCLC patients. Most patients with NSCLC are in a hypercoagulable state, which is related to age, tumor invasion and metastasis, recurrence, and treatment. Regular monitoring of plasma D-D levels can facilitate early diagnosis of a hypercoagulable state and timely and appropriate use of anticoagulants, to avoid or reduce complications such as venous thromboembolism in NSCLC patients and to prevent the risk of bleeding caused by excessive anticoagulants. Clinicians can choose the treatment with less harm and maximum benefit for NSCLC patients based on the plasma D-D level. When in a hypercoagulable state, the body's blood viscosity increases, making it more conducive to the growth and infiltration of tumor cells. Our study shows that the recurrence and metastasis of NSCLC are related to coagulation indexes, which provides a theoretical basis for the early diagnosis and treatment of recurrent and metastatic NSCLC.
本研究旨在探讨非小细胞肺癌(NSCLC)患者不同年龄血浆 D-二聚体(D-D)水平与年龄、转移、TNM 分期(肿瘤-淋巴结-转移分类)和治疗的相关性,以便早期发现高凝状态,选择合适的治疗方法,并使用合适的抗凝剂,从而预防血栓形成和因抗凝过度引起的并发症;减少或避免老年 NSCLC 患者的血栓或弥散性血管内凝血(DIC)等并发症。通过监测 NSCLC 患者血浆 D-D 水平,可以预测早期复发和转移,并评估 TNM 分期。
选择山西白求恩医院 2014 年 3 月至 2020 年 10 月收治的首次确诊未经任何治疗的 NSCLC 患者 670 例为实验组,同时选取该院体检中心同期健康体检者 950 例为对照组。收集所有初次确诊的 NSCLC 患者的资料,并根据转移、TNM 分期、治疗方法和病理类型进行分组,分析与血浆 D-D 水平的相关性。采用 ACL TOP700 全自动凝血分析仪免疫比浊法检测血浆 D-D 水平。进一步根据不同治疗方法将患者分为两组,分析不同治疗周期化疗和靶向治疗患者血浆 D-D 水平的差异。分析健康对照组中 D-D 水平与年龄的相关性,分析 NSCLC 患者与健康对照组同年龄段 D-D 水平的差异。
实验组和对照组的所有数据均呈正态分布。实验组平均年龄为 61.31±6.23(范围:36-92)岁,对照组平均年龄为 61.14±11.12(范围:35-85)岁。实验组和对照组的性别差异无统计学意义(>0.05)。NSCLC 患者的血浆 D-D 水平明显高于健康对照组(<0.05)。不同性别 NSCLC 患者的血浆 D-D 水平差异无统计学意义(>0.05),不同性别健康对照组的血浆 D-D 水平也无统计学差异(>0.05)。30-59 岁和 60-69 岁组、60-69 岁和 70-79 岁组、70-79 岁和≥80 岁组之间的 D-D 水平差异有统计学意义(<0.05)。≤79 岁患者的 D-D 水平随年龄增加而增加,但>80 岁患者的 D-D 水平降低。Pearson 相关性分析显示,79 岁以下 NSCLC 患者的 D-D 水平与年龄呈正相关(<0.05)。四组年龄组间 D-D 水平差异有统计学意义(<0.05),健康对照组 D-D 水平随年龄增长呈上升趋势。NSCLC 患者与同年龄组健康对照组的 D-D 水平差异有统计学意义(<0.05),提示 NSCLC 患者的 D-D 水平明显高于同年龄组健康人群。无转移 NSCLC 患者、有转移 NSCLC 患者和健康人群的 D-D 水平差异有统计学意义(<0.05),有转移的患者 D-D 水平最高,健康人群 D-D 水平最低。不同 TNM 分期的 NSCLC 患者的 D-D 水平差异有统计学意义(<0.05),晚期患者的 D-D 水平较高。NSCLC 患者治疗前后的 TNM 分期和 D-D 水平差异有统计学意义(<0.05)。早期患者治疗后 D-D 水平变化更明显。早期阶段与治疗后 D-D 水平变化明显相关,差异有统计学意义(<0.05)。晚期阶段与治疗后 D-D 水平变化较小相关,差异无统计学意义(>0.05)。化疗或靶向治疗四个周期前后的血浆 D-D 水平均高于健康对照组,差异有统计学意义(<0.05)。化疗后患者的 D-D 水平明显低于化疗前(<0.05),但靶向治疗前后差异无统计学意义(>0.05)。化疗第一周期后的 D-D 水平高于化疗前。化疗后第三和第四周期的 D-D 水平明显低于化疗前(<0.05)。化疗前后 D-D 水平无统计学差异(>0.05)。
建议将凝血试验指标纳入 NSCLC 患者的治疗方案评估中。大多数 NSCLC 患者处于高凝状态,这与年龄、肿瘤侵袭和转移、复发和治疗有关。定期监测血浆 D-D 水平有助于早期发现高凝状态,及时合理使用抗凝剂,避免或减少 NSCLC 患者静脉血栓栓塞等并发症的发生,防止抗凝过度引起的出血风险。临床医生可以根据血浆 D-D 水平为 NSCLC 患者选择危害最小、获益最大的治疗方案。高凝状态时,机体血液黏度增加,更有利于肿瘤细胞的生长和浸润。本研究表明 NSCLC 的复发和转移与凝血指标有关,为 NSCLC 复发性和转移性的早期诊断提供了理论依据。