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. 2022 Mar 2:9:853941.
doi: 10.3389/fmed.2022.853941. eCollection 2022.

Circulating D-Dimers Increase the Risk of Mortality and Venous Thromboembolism in Patients With Lung Cancer: A Systematic Analysis Combined With External Validation

Jing Li  1 , Shanle Yan  2 , Xiaohui Zhang  3 , Mengqi Xiang  4 , Chuanhua Zhang  5 , Ling Gu  3 , Xiaoying Wei  1 , Chuanyun You  3 , Shenhua Chen  3 , Daxiong Zeng  1 , Junhong Jiang  1
Affiliations

Circulating D-Dimers Increase the Risk of Mortality and Venous Thromboembolism in Patients With Lung Cancer: A Systematic Analysis Combined With External Validation

Jing Li et al. Front Med (Lausanne). .

Abstract

Background: D-dimer is a fibrin-degrading substance that is soluble and whose degradation is produced by plasma protein-mediated degradation of cross-linked fibrin. Previous investigations have shown a link between D-dimer and the mortality in lung cancer patients. However, different investigations varied whether D-dimer could predict prognosis in these patients.

Methods: A meta-analysis and systematic review of all available cohort studies were performed on the link between circulating D-dimer levels and survival of lung cancer patients. Relevant studies were searched in Embase, Cochrane Library, and PubMed databases. Data from 540 lung cancer patients from the First Hospital of Soochow University and Sichuan Cancer Hospital were used for external validation.

Results: We finally obtained 19 eligible cohort studies with pooled HR showing that high D-dimer levels contribute to death in tumor group (HR 1.62, 95% CI: 1.39-1.88, I2 = 75.0%). Further stratified analysis showed that higher circulating D-dimer in the advanced lung cancer group was linked to a 1.91-fold risk (HR = 2.91, 95% CI: 2.24-3.78, I2 = 6.0%). Incorporation of other variables, including days of follow-up, country, design, public year, population, disease status, and quality score, into the meta-regression model, indicated that disease status was an additional source of heterogeneity (p < 0.001). External validation of 540 patients also showed that high levels of D-dimer showed a higher risk of overall mortality (HR 1.39, 95% CI: 1.13-1.72, p = 0.002) and VTE events (HR 3.98, 95% CI: 1.99-8.70, p = 0.002) in lung cancer patients.

Conclusions: High circulating plasma D-dimer levels independently predict long-term prognosis and the risk of venous thromboembolism in lung cancer.

Keywords: D-dimer; VTE; lung cancer; meta-analysis; mortality.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of projects' selection designed by PRISMA.
Figure 2
Figure 2
Forest plot (Fixed and random-effects model) for the link between plasma D-dimer levels (highest vs. lowest category) and lung cancer-associated mortality. Subgroup analysis is grouped by disease states (non-advanced lung cancer and advanced lung cancer).
Figure 3
Figure 3
(A) Funnel plot for the link between plasma D-dimer levels (highest vs. lowest category) and lung cancer-associated mortality. (B) Filled funnel plot and meta trim-and-fill model. The blue dots indicate that these included studies require a corresponding study for correction, thus reducing bias.
Figure 4
Figure 4
Kaplan-Meier curves for NSCLC patients with different factors. (A) Kaplan-Meier curves for OS in patients in the VTE and non-VTE groups. (B) Kaplan-Meier curves for OS in different D-dimer levels.
Figure 5
Figure 5
Forest plot for multifactorial analysis of different endpoints in patients with NSCLC. (A) Forest plot for multifactor analysis of the risk of overall mortality. (B) Forest plot for multifactor analysis of the risk of VTE events.
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