Assessment of the association between D-dimer levels and clinicopathological characteristics of pancreatic cancer and its role in prognosis: a systematic review and meta-analysis

doi:10.21203/rs.3.rs-3119508/v1

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Systematic Review

Assessment of the association between D-dimer levels and clinicopathological characteristics of pancreatic cancer and its role in prognosis: a systematic review and meta-analysis

https://doi.org/10.21203/rs.3.rs-3119508/v1

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published 01 Mar, 2024

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Background: According to previous studies, D-dimer levels are associated with prognosis in patients with pancreatic cancer (PC). However, the current results are limited and controversial. Therefore, we conducted this meta-analysis to assess the relationship between D-dimer levels and the prognosis and pathological characteristics of patients with PC.

Method: A computer search of PubMed, Embase, The Cochrane Library, Web Of Science, CBM, VIP, CNKI and Wanfang databases was conducted to identify available studies. The association between pre-treatment d -dimer levels and the prognosis of PC patients was assessed using a combined hazard ratio (HR) and 95% confidence interval (CI). The combined odds ratio (OR) and 95% confidence in CI were applied to assess the relationship between D-dimer levels and the pathological characteristics of patients with PC. For all of the statistical analyses, Stata 12.0 software was used.

Result: A total of 13 studies involving 2777 patients were included in this meta-analysis. The results showed that elevated pre-treatment d -dimer levels were significantly associated with worsening OS (HR = 1.46 95% CI: 1.34-1.59; p＜0.001). We also performed subgroup analyses based on sample size, d -dimer threshold, follow-up time and source of HR to further validate the prognostic value of pre-treatment d -dimer levels in PC. In addition, according to the analysis, high pre-treatment d -dimer levels in PC patients were associated with late tumour stage (OR = 4.78, 95% CI 1.73-13.20, p＜0.005), larger tumours (OR = 1.72, 95% CI 1.25 ~ 2.35, p＜0.005) and distant metastases in tumours (OR = 5.06, 95% CI 2.45- 10.43, p＜0.005) were significantly associated. In contrast, other clinicopathological factors, including age, sex and lymph node metastasis, were not associated with d -dimer levels.

Conclusion: High levels of d-dimer prior to treatment are associated with poor prognosis in patients with PC and are associated with more advanced tumour stage, larger tumours and the occurrence of distant metastases. Plasma d-dimer levels can be used as a biomarker of prognosis in patients with PC.

General Surgery

Oncology

Gastroenterology & Hepatology

pancreatic cancer

D-dimer

prognostic

biomarker

With an ageing population,PC has become one of the leading causes of cancer deaths worldwide, and its global burden has more than doubled in the last 25 years¹. It is expected to become the second leading cause of cancer death in the United States by 2030². However, PC remains a clinically challenging cancer because not only is it most of the patients already in advanced stages at the time of diagnosis, but many patients are already resistant to chemotherapy³. Therefore, the prognosis of PC is very poor. Despite some achievements in the diagnosis and treatment of PC in recent years as the pathogenesis of the disease continues to be researched and explored, the prognosis for this cancer remains frustratingly poor⁴. Therefore, the search for effective prognostic factors and treatment strategies plays a crucial role in improving the prognosis of PC.

Coagulation and fibrinolytic activation have been reported to be commonly associated with most malignancies and are associated with angiogenesis, tumor cell invasion, tumor progression and metastatic spread⁵. D-dimer is a degradation product of cross-linked fibrin, a marker of hypercoagulation and thrombosis, while its elevation is also associated with the risk of cancer⁶. In the past few years, much attention has been paid to the relationship between elevated D-dimer levels and tumor prognosis and thromboembolism formation^7–9.

D-dimer elevated levels have also been found in PC patients and associated with a poor prognosis. In past reports, higher levels of D-dimer were associated with a substantially increased risk of Venous Thromboembolism(VTE) and death in PC¹⁰. It has also been reported that preoperative high levels of D-dimer can be used to predict the unresectability of patients ' tumors and prevent further damage¹¹. However, studies on the relationship between D-dimer levels and PC prognosis are limited, and the results have been controversial. Therefore, we collected published data for a meta-analysis to further identify and validate the association between D-dimer levels and PC prognosis.

2.1 Registration

This research was registered on PROSPERO (ID: 42023389235).

2.2 Literature search strategy

The databases of PubMed, Embase, The Cochrane Library, Web Of Science, CBM, VIP, CNKI and Wanfang were searched by computer from the date of creation to August 22, 2022. In addition, references to the literature were retrospectively included to complement the acquisition of relevant literature. The search was executed using a combination of subject terms and free words.Our search items included: (“D-dimer” OR “D dimer” OR “D-dimers” OR “D dimers” OR “DD”) AND (“pancreatic neoplasms” OR “pancreatic neoplasm” OR “pancreas cancer*” OR “pancreatic cancer*” OR “cancer of pancreas” OR “cancer of the pancreas” OR “pancreatic adenocarcinoma” OR “pancreatic carcinoma*” OR “pancreas carcinoma*” OR “pancreatic ductal adenocarcinoma” OR “PDAC”).

2.3 Eligibility criteria

The inclusion criteria were as follows: (a) pre-treatment plasma D-dimer levels were measured in PC patients; (b) patients were divided into two high and low groups according to D-dimer levels; (c) PC patients who have undergone surgery, targeted therapy or radiotherapy; (d) the relationship between D-dimer levels and overall survival (OS) or clinicopathological characteristics is assessed in the text; (e) the hazard ratio (HR) and 95% confidence interval (CI) of the study can be obtained directly or indirectly.

The exclusion criteria were as follows: (a) case reports, conference abstracts, reviews and letters; (b) unable to obtain useful data; (c) repeat publication studies; (d) patient has received or is receiving anticoagulant therapy at the time of plasma D-dimer collection.

2.4 Date extraction

Two investigators independently screened the literature, extracted data, and cross-checked them. In case of disagreement, it was resolved through discussion or consultation with a third party. Literature was screened by first reading the title and abstract of the article, and after excluding apparently irrelevant literature, the full article was further read to determine inclusion. If necessary, the original study authors were contacted by email or telephone to obtain information that was not identified but was important to this study. Data extraction included: first author, year of publication, total sample size, D-dimer detection methods, cut-off value, treatment measures, outcome indicators, and follow-up time. The primary outcome indicator was OS. The subsidiary outcome indicators included age, gender, TumorNodeMetastasis(TNM) stage, lymph node metastasis (LNM), tumor size, degree of differentiation, and distant metastasis.

2.5 Quality assessment

The quality of the included studies was evaluated independently by two researchers employing the Newcastle-Ottawa Scale (NOS). The NOS scores ranged from 1 to 9, with scores higher than 6 being considered as high quality studies.

2.6 Statistical methods

Statistical analysis was performed using Stata 12.0 software. The association of D-dimer with survival was determined by HRs, and the association of D-dimer with clinicopathological features was determined by ORs. Heterogeneity between the results of the included studies was analyzed using the chi-squared test, while the magnitude of heterogeneity was determined quantitatively in combination with I². A fixed-effects model was used if there was no statistical heterogeneity (P_Q ≥ 0.1, I² ≤ 50%), and a random-effects model was used if there was statistical heterogeneity (P_Q < 0.1, I² > 50%) among the study outcomes. Significant clinical heterogeneity was addressed using methods such as subgroup analysis or sensitivity analysis. The presence of publication bias was evaluated using Begg’s funnel plot and Egger’s test. P < 0.05 was considered statistically significant.

3.1 Study search

Through our search of various national and international databases, we identified a total of 797 studies, of which 554 remained after eliminating duplicates. Based on the titles and abstracts, we excluded 457 articles that were not relevant to the content of the study and conducted a full comprehensive evaluation of the remaining 97 articles. After assessing the full-text literature for eligibility, we excluded 84 studies, of which 10 were cases or reviews, 69 did not have sufficient data, and 5 were animal studies. Finally, we included 13 studies that could be used for the meta-analysis^10,12−23. The flow chart of the screening process is shown in Fig. 1.

3.2 Characteristics of eligible studies

The final 13 articles (involving 2777 patients) were included in this meta-analysis. Of these, 11 studies were conducted in China, 2 studies were from Austria. Eleven of the included studies were retrospective and two were prospective, with samples ranging from 37 to 1351. D-dimer assays included enzyme-linked immunosorbent reagents, immunoturbidimetric assays and enzyme-linked immunofluorescence assays. The specific characteristics of the included studies are shown in Table 1.

3.3 Quality assessment and risk of bias

We evaluated the quality of the 13 studies included in the meta-analysis according to the NOS scale. The results of the quality assessment are presented in Table 1. Eleven of the 13 studies we included were assessed as high quality and only two were rated as moderate quality, so indicating that we had a relatively low risk of bias in all studies.

3.4 Association of Pretreatment D-dimer Level With OS

Of the 13 studies we included, 11 of them analysed the relationship between D-dimer and OS. We compared the OS of PC patients with higher D-dimer levels with those with lower D-dimer levels by dividing the patients into high and low groups according to their pre-treatment D-dimer levels. Our meta-analysis study found that because no significant heterogeneity was found (I² = 35.3%), a fixed effects model was used. The combined HR was 1.46 (95% CI 1.34–1.59; p < 0.001), indicating that pre-treatment high D-dimer levels were significantly associated with poor OS in patients with PC.(Fig. 2)

In addition, we performed subgroups analysis according to sample size (≥ 100 or < 100), follow-up time (≥ 60 months or < 60 months), HR availability (reported in the text or extracted in survival curves) and D-dimer cut-off values (not reported or ≤ 0.55 ng/ml or > 0.55 ng/ml) to further explore the relationship between D-dimer levels and OS in PC patients correlation. We found similar results to those pooled by analyzing the above four subgroups, and the above results suggest that higher pre-treatment D-dimer in PC patients may be associated with poorer OS, and that none of these factors affect the prognostic value of pre-treatment D-dimer in PC patients.(Fig. 3)

3.5 Association of Pretreatment D-dimer Level With clinicopathological parameters

Out of the 13 included articles, a total of 8 articles were identified according to our comprehensive analysis providing pre-treatment D-dimer levels in PC patients with clinicopathological parameters including age, gender, tumor stage, tumor size, lymph node metastasis, degree of differentiation and distant metastasis. The analysis was conducted using ORs and their 95% CIs. According to the analysis, high levels of pre-treatment D-dimer in PC patients were associated with advanced tumor stage (OR = 4.78, 95% CI 1.73–13.20, p < 0.005), larger tumor (OR = 1.72, 95% CI 2.57–8.88, p < 0.005) and early distant metastases (OR = 5.06, 95% CI 2.45–10.43, p < 0.005) were significantly associated. However, differences in age (OR = 1.17, 95% CI 0.89–1.53, p = 0.272), gender (OR = 0.90, 95% CI 0.69–1.17, p = 0.430) and early lymph node metastasis (OR = 1.78, 95% CI 0.97–3.25, p = 0.062) were not statistically significant. (Fig. 4)

3.6 Sensitivity analysis

To assess the reliability of the results of the correlation between untreated D-dimer levels and OS in patients with PC, we performed a sensitivity analysis in which we used a case-by-case exclusion method and then did not find that any of the studies changed the results, so we can assume that high levels of D-dimer in untreated PC patients are reliably associated with poorer OS.We also used the results of correlation between D-dimer levels and clinicopathological features for sensitivity analysis. Heterogeneity in the association of high levels of d -dimer with tumor stage in untreated PC patients was also completely eliminated (P_Q = 0.390, I² = 0.0%) after exclusion of the Liu et al. and Zhen et al. studies, with no effect on outcome (OR = 2.19 95% CI 1.27–3.76 p＜0.005). In sensitivity analyses of LNM, the heterogeneity of the correlation between high levels of d -dimer PC patients and early lymph node metastasis was also significantly reduced after removal of the Lv2022 and zen2021 studies (P_Q = 0.786 I² = 0.0%) and had no effect on the results (OR = 1.08 95% CI 0.79–1.48 p = 0.634). (Fig. 5)

3.7 Analysis of publication bias

In addition, we analyzed the publication bias of the correlation between D-dimer levels and OS in untreated PC patients included in the study using Begg's funnel plot, For OS, we can see from the funnel plot asymmetry that there is some publication bias. Using the scissors method, the funnel plot became symmetrical after filling in five hypothetical unpublished papers. and the pooled HR and 95% CI remained stable (HR = 3.97 95% CI 3.55–4.48, p < 0.001) Finally, after including five dummy studies, The analysis remained robust and did not reverse, indicating that our results are reliable. (Fig. 6)

Despite the declining overall cancer mortality rate, PC remains a highly lethal malignancy and is expected to be the second leading cause of cancer death in the United States within the next 20 to 30 years. In the United States, the 5-year survival rate at diagnosis is 10%, as approximately 80–85% of patients have disease that has become unresectable or metastatic by the time it is detected²⁴. Although various treatments including radiotherapy and chemotherapy have greatly improved the survival rates of PC patients over the past few decades due to rapid advances in surgical techniques, PC still poses a huge health problem for people worldwide due to its extremely insidious and malignant nature²⁵. Therefore, we believe that to improve the survival and quality of life of PC patients, biomarkers that can predict the prognosis and pathological features of PC patients must be found as soon as possible^26–28. Therefore more and more researchers are focusing on finding biomarkers of prognosis and want to provide guidance for the future treatment of PC.

In the management of PC, we have found that carbohydrate antigen 19 − 9 (CA19-9) is considered to be the best serological biomarker for the diagnosis of PC to date, however, most studies that have endorsed the use of CA19-9 as a complementary test for the diagnosis of PC acknowledge its lack of specificity or sensitivity, and its use in clinical practice is primarily diagnostic rather than prognostic²⁹. Meanwhile, different miRNAs expression profiles were found to correlate with the stage of PC and to have potential as biomarkers and prognostic markers in the study by Daoud et al³⁰. CircRNAs have also been reported to play a stable and sensitive biomarker role in the prognosis of PC in the study by Fathizadeh et al³¹. However, despite the potential of both miRNAs and circRNAs as biomarkers, the difficulty of detection methods and the high cost of detection have prevented their large-scale clinical use. By comparison, every patient with PC is asked to test for D-dimers before being admitted to hospital for treatment.D-dimers are involved in the regulation of a variety of cancer processes^32–34. Therefore, in recent years, many studies have explored the relationship between D-dimer levels and the prognosis of PC patients^11,22,34,35. However, the role of D-dimers in PC remains controversial. In the Demir et al. study, D-dimer was not an accurate prognostic indicator in patients with PC who underwent R1 resection, possibly because patients with R1 resection were more prone to local recurrence compared to those with R0 resection, which would have an independent negative impact on prognosis³⁶. In some studies, although D-dimer has been reported as a prognostic indicator for patients with PC, its clinical application remains controversial due to the limited size of the studies and the lack of adjustment for risk factors¹¹. In these meta-analyses, D-dimer has been shown to predict poor prognosis in lung, breast and gastric cancers^37–39.

This meta-analysis explored the relationship between plasma D-dimer and the prognosis of patients with PC and the relationship with pathological features. The results suggest that D-dimer, as a potent coagulation factor, has great potential to be a biomarker for predicting the prognosis of PC patients and to provide guidance to clinicians for anticoagulation therapy. In our study, we assessed the significance of plasma D-dimer levels in PC. Patients with high plasma D-dimer levels had a poorer OS prognosis compared to those with normal plasma D-dimer levels. Therefore, we believe that this meta-analysis can confirm the prognostic significance of plasma D-dimer levels in pancreatic tumors. We further explored the relationship between d -dimer and OS in PC patients based on sample size, follow-up time, HR availability and d -dimer threshold levels in order to improve the credibility of the results. We obtained similar results to the pooled results by analyzing the four subgroups mentioned above. We also analyzed untreated pre-d -dimer levels with clinicopathological characteristics of PC patients and we found that high pre-treatment d -dimer levels in PC patients were associated with advanced tumor stage, larger tumors and early distant metastases were significantly associated. These provide further evidence for the prognostic role of D-dimer in patients with PC. The exact mechanism by which D-dimers contribute to the poor prognosis of PC is not known. Tumor cells convert fibrinogen to fibrin. D-dimer is a stable fibrinogen degradation product that has been shown to be associated with tumor progression and elevated plasma D-dimer levels may reflect ongoing fibrinogen metabolism in an actively remodeling tumor stroma⁴⁰. Secondly, tumor cells can express large amounts of tissue factor that will activate the coagulation cascade, ultimately leading to fibrin deposition, tumor growth and tumor cell metastasis. In addition, plasma D-dimer levels may reflect the presence of micrometastases or round tumor cells, which may be responsible for tumor recurrence⁴¹. But we still want to know which process of PC is altered by D-dimer that leads to poor prognosis in patients, so we can reduce D-dimer levels to improve prognosis in patients with PC.

At the same time, there are a number of limitations in this meta-analysis. Firstly, the studies we included were only retrospective studies which may have some bias. Secondly, most of the studies we included were from China, which may lead to regional bias. Finally, inconsistencies in assay methods, reagents, and anticoagulant types may lead to large differences in absolute D-dimer values, resulting in high heterogeneity of results in the literature.

The results of this meta-analysis showed that high levels of plasma D-dimer before treatment were associated with poor prognosis in patients with PC and correlated with advanced tumor stage, larger tumors and early distant metastases. This suggests that D-dimer has potential value in the diagnosis and treatment of PC. However, the current findings have limitations and further multicenter studies with large samples are recommended to validate the relationship between D-dimer and PC.

CI: Confidence interval

HR: Hazard ratio

LNM: Lymph node metastasis

NOS: Newcastle–Ottawa scale

OR: Odds ratio

OS: Overall survival

PC：pancreatic cancer

PDAC: pancreatic ductal adenocarcinoma

VTE: Venous Thromboembolism

Conflict of Interest

The authors declare no competing interests.

Author contributions

The study was conceptualized by BW; conducted by DW, JW, and YZ; GZ and BW extracted the necessary data; XZ and MY carried out the statistical analysis; GZ and BW prepared a draft; and was evaluated by HC.

Acknowledgments

We appreciate the work of the researchers and the study participants.

Data Availability Statement

The corresponding author will provide the datasets used and/or analyzed during the current work upon reasonable request.

Funding

This study was supported by the Central to guide local scientific and Technological Development (ZYYDDFFZZJ-1), Natural Science Foundation of Gansu Province, China (No.18JR3RA052), Lanzhou Talent Innovation and Entrepreneurship Project Task Contract (No.2016-RC-56), Gansu Da Vinci robot high-end diagnosis and treatment team construction project, and National Key Research and Development Program (No.2018YFC1311500).

Klein AP. Pancreatic cancer epidemiology: understanding the role of lifestyle and inherited risk factors. Nature reviews Gastroenterology & hepatology. 2021;18(7):493-502.
Park W, Chawla A, O'Reilly EM. Pancreatic Cancer: A Review. Jama. 2021;326(9):851-862.
Wood LD, Canto MI, Jaffee EM, Simeone DM. Pancreatic Cancer: Pathogenesis, Screening, Diagnosis, and Treatment. Gastroenterology. 2022;163(2):386-402.e381.
Huang X, Zhang G, Tang TY, Gao X, Liang TB. Personalized pancreatic cancer therapy: from the perspective of mRNA vaccine. Military Medical Research. 2022;9(1):53.
Ay C, Dunkler D, Pirker R, et al. High D-dimer levels are associated with poor prognosis in cancer patients. Haematologica. 2012;97(8):1158-1164.
Simes J, Robledo KP, White HD, et al. D-Dimer Predicts Long-Term Cause-Specific Mortality, Cardiovascular Events, and Cancer in Patients With Stable Coronary Heart Disease: LIPID Study. Circulation. 2018;138(7):712-723.
Giaccherini C, Marchetti M, Masci G, et al. Thrombotic biomarkers for risk prediction of malignant disease recurrence in patients with early stage breast cancer. Haematologica. 2020;105(6):1704-1711.
Liang S, Tang W, Ye S, Xiang L, Wu X, Yang H. Incidence and risk factors of preoperative venous thromboembolism and pulmonary embolism in patients with ovarian cancer. Thrombosis research. 2020;190:129-134.
Posch F, Riedl J, Reitter EM, et al. Dynamic assessment of venous thromboembolism risk in patients with cancer by longitudinal D-Dimer analysis: A prospective study. Journal of thrombosis and haemostasis : JTH. 2020;18(6):1348-1356.
Moik F, Prager G, Thaler J, et al. Hemostatic Biomarkers and Venous Thromboembolism Are Associated With Mortality and Response to Chemotherapy in Patients With Pancreatic Cancer. Arteriosclerosis, thrombosis, and vascular biology. 2021;41(11):2837-2847.
Durczynski A, Kumor A, Hogendorf P, Szymanski D, Grzelak P, Strzelczyk J. Preoperative high level of D-dimers predicts unresectability of pancreatic head cancer. World journal of gastroenterology. 2014;20(36):13167-13171.
LV ZP, Mao RX, Su LDKZQM, Geng C, He TY. Diagnostic value of preoperative D-dimer and neutrophil-to-lymphocyte ratio combined with CA19-9 for pancreatic tumor. Chinese journal of bases and clinics in general surgery. 2022;29(4):470-474.
Liu Y, Dai YZ, Yao WY, Jiang TH, Li QY. Correlation analysis of plasma D-Dimer level with survival and prognosis in pancreatic cancer. Contemporary Medicine. 2022;28(3).
Hu CD, Wang J, Zheng LP, Chen XJ, Fei FM, Shen YY. Correlation between plasma D-dimer and clinicopathological features and prognosis in patients with pancreatic cancer Journal of Hepatopancreatobiliary Surgery. 2022;34(4).
Zheng YF, Zhang H, F ., Du JP, Wu CL, ., Yan HX, Chen SY. Preoperative D-dimer level and neutrophil to lymphocyte ratio score for evaluating prognosis in patients with pancreatic ductal adenocarcinoma. Zhejiang Medical Journal. 2021;43(13).
Zhang LP, Ren H, Du YX, Zheng XH, Zhang ZM, Wang CF. Combination of preoperative fibrinogen and D-dimer as a prognostic indicator in pancreatic ductal adenocarcinoma patients undergoing R0 resection. World journal of gastrointestinal surgery. 2021;13(3):279-302.
Xu P, Wang X, Qian J, Li Z, Yao J, Xu A. The prognostic evaluation of CA19-9, D-dimer and TNFAIP3/A20 in patients with pancreatic ductal adenocarcinoma. Medicine. 2021;100(6):e24651.
Chen H, Li F, Zou S, et al. Preoperative plasma D-dimer independently predicts survival in patients with pancreatic ductal adenocarcinoma undergoing radical resection. World journal of surgical oncology. 2021;19(1):166.
Cao JL, Wang X, Zheng L, Xu HM, Chen LL, Gao LM. Value of D-dimer, carbohydrate antigen 199 and insulin-like growth factor binding protein 2 for postoperative monitoring and survival time prediction in patients with resectable pancreatic cancer. Cancer Research and clinic. 2020;32(7).
Dai H, Zhou H, Sun Y, et al. D-dimer as a potential clinical marker for predicting metastasis and progression in cancer. Biomedical reports. 2018;9(5):453-457.
Sun W, Ren H, Gao CT, et al. Clinical and Prognostic Significance of Coagulation Assays in Pancreatic Cancer Patients With Absence of Venous Thromboembolism. American journal of clinical oncology. 2015;38(6):550-556.
Liu P, Zhu Y, Liu L. Elevated pretreatment plasma D-dimer levels and platelet counts predict poor prognosis in pancreatic adenocarcinoma. OncoTargets and therapy. 2015;8:1335-1340.
Ay C, Dunkler D, Pirker R, et al. High D-dimer levels are associated with poor prognosis in cancer patients. Haematologica-the Hematology Journal. 2012;97(8):1158-1164.
Mizrahi JD, Surana R, Valle JW, Shroff RT. Pancreatic cancer. Lancet (London, England). 2020;395(10242):2008-2020.
Strobel O, Neoptolemos J, Jäger D, Büchler MW. Optimizing the outcomes of pancreatic cancer surgery. Nature reviews Clinical oncology. 2019;16(1):11-26.
Li Z, Cao S, Sun Y, et al. TIPE3 is a candidate prognostic biomarker promoting tumor progression via elevating RAC1 in pancreatic cancer. Molecular cancer. 2022;21(1):160.
Jin F, Yang L, Wang W, et al. A novel class of tsRNA signatures as biomarkers for diagnosis and prognosis of pancreatic cancer. Molecular cancer. 2021;20(1):95.
Luo G, Jin K, Deng S, et al. Roles of CA19-9 in pancreatic cancer: Biomarker, predictor and promoter. Biochimica et biophysica acta Reviews on cancer. 2021;1875(2):188409.
O'Neill RS, Stoita A. Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket? World journal of gastroenterology. 2021;27(26):4045-4087.
Daoud AZ, Mulholland EJ, Cole G, McCarthy HO. MicroRNAs in Pancreatic Cancer: biomarkers, prognostic, and therapeutic modulators. BMC cancer. 2019;19(1):1130.
Fathizadeh H, Hallajzadeh J, Asemi Z. Circular RNAs as diagnostic biomarker in pancreatic cancer. Pathology, research and practice. 2020;216(9):153075.
Stender MT, Larsen TB, Sørensen HT, Thorlacius-Ussing O. Preoperative plasma D-dimer predicts 1-year survival in colorectal cancer patients with absence of venous thromboembolism (VTE): a prospective clinical cohort study. Journal of thrombosis and haemostasis : JTH. 2012;10(10):2027-2031.
Lee MJ, Weng CM, Chao W, et al. Platelet Activation in High D-Dimer Plasma Plays a Role in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Mutant Lung Adenocarcinoma. Frontiers in oncology. 2022;12:876051.
Liang YJ, Mei XY, Zeng B, et al. Prognostic role of preoperative D-dimer, fibrinogen and platelet levels in patients with oral squamous cell carcinoma. BMC cancer. 2021;21(1):122.
Watanabe A, Araki K, Hirai K, et al. A Novel Clinical Factor, D-Dimer Platelet Multiplication, May Predict Postoperative Recurrence and Prognosis for Patients with Cholangiocarcinoma. Annals of surgical oncology. 2016;23(Suppl 5):886-891.
Demir IE, Jäger C, Schlitter AM, et al. R0 Versus R1 Resection Matters after Pancreaticoduodenectomy, and Less after Distal or Total Pancreatectomy for Pancreatic Cancer. Annals of surgery. 2018;268(6):1058-1068.
Li J, Yan S, Zhang X, et al. Circulating D-Dimers Increase the Risk of Mortality and Venous Thromboembolism in Patients With Lung Cancer: A Systematic Analysis Combined With External Validation. Frontiers in medicine. 2022;9:853941.
Lu Y, Zhang L, Zhang Q, et al. The association of D-dimer with clinicopathological features of breast cancer and its usefulness in differential diagnosis: A systematic review and meta-analysis. PLoS One. 2019;14(9):e0221374.
Lin Y, Liu Z, Qiu Y, et al. Clinical significance of plasma D-dimer and fibrinogen in digestive cancer: A systematic review and meta-analysis. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2018;44(10):1494-1503.
Blackwell K, Haroon Z, Broadwater G, et al. Plasma D-dimer levels in operable breast cancer patients correlate with clinical stage and axillary lymph node status. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2000;18(3):600-608.
Fukumoto K, Taniguchi T, Usami N, et al. Preoperative plasma D-dimer level is an independent prognostic factor in patients with completely resected non-small cell lung cancer. Surgery today. 2015;45(1):63-67.

Table 1: Characteristics of studies in this meta-analysis.

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Assessment of the association between D-dimer levels and clinicopathological characteristics of pancreatic cancer and its role in prognosis: a systematic review and meta-analysis

Status:

Journal Publication

Version 1

Abstract

Figures

1. Introduction

2. Materials and methods

2.1 Registration

2.2 Literature search strategy

2.3 Eligibility criteria

2.4 Date extraction

2.5 Quality assessment

2.6 Statistical methods

3. Results

3.1 Study search

3.2 Characteristics of eligible studies

3.3 Quality assessment and risk of bias

3.4 Association of Pretreatment D-dimer Level With OS

3.5 Association of Pretreatment D-dimer Level With clinicopathological parameters

3.6 Sensitivity analysis

3.7 Analysis of publication bias

4. Discussion

5. Conclusion

Abbreviations

Declarations

References

Table

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