Preoperative D‑dimer level and prognosis in patients diagnosed with gastric cancer and undergoing gastric cancer radical surgery: A retrospective cohort study

Zhao,Yuanzheng; Han,Jiaqi; Yang,Rong; Wang,Shuqin; Zhang,Kai; Lu,Hongxia

doi:10.3892/ol.2024.14810

Preoperative D‑dimer level and prognosis in patients diagnosed with gastric cancer and undergoing gastric cancer radical surgery: A retrospective cohort study

Authors:
- Yuanzheng Zhao
- Jiaqi Han
- Rong Yang
- Shuqin Wang
- Kai Zhang
- Hongxia Lu
View Affiliations

Affiliations: Department of Clinical Medicine, Fenyang College Shanxi Medical University, Lvliang, Shanxi 032200, P.R. China, Department of Gastroenterology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030013, P.R. China, Department of Gastroenterology, Second Hospital of Jilin University, Changchun, Jilin 130000, P.R. China
Published online on: November 19, 2024 https://doi.org/10.3892/ol.2024.14810
Article Number: 64
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Gastric cancer, one of the most aggressive tumors affecting the digestive tract, has seen a rise in both incidence and mortality rates in recent years, with a lack of clear prognostic indicators. D‑dimer, a byproduct of fibrin degradation, is a conventional coagulation biomarker that has been investigated as a potential adverse prognostic factor for postoperative cancer patients. However, conflicting results exist, with some studies suggesting that D‑dimer is an independent risk factor for the postoperative prognosis of gastric cancer, and others suggesting that there is no significant association between D‑dimer level and gastric cancer prognosis. This controversy underscores the need for further research to determine the true influence of D‑dimer level on the prognosis of postoperative cancer patients, including exploring the linear and non‑linear associations, and identifying optimal critical values before surgery. The present study aimed to assess the association between preoperative D‑dimer levels and 5‑year overall survival (OS) rate in patients undergoing radical surgery for gastric cancer. Data was analyzed from patients diagnosed with gastric cancer who underwent a radical gastrectomy at Shanxi Cancer Hospital (Taiyuan, China) in 2017 and were followed up for 5 years until December 2022. Preoperative D‑dimer levels and tumor‑related indicators were collected as covariates from hospital records, with patient follow‑up information obtained from the hospital's tracking system. Utilizing multivariate Cox regression, curve fitting and inflection point analysis, the present study sought to investigate the link between preoperative D‑dimer levels and 5‑year OS rate following radical surgery for gastric cancer. After strict admission and exclusion procedures, a total of 133 patients were included in the study and were then classified based on D‑dimer level. Based on the mean value, the D‑dimer levels were segregated into two distinct cohorts: The D‑dimer_high group (n=66) and the D‑dimer_low group (n=67). Cox multiple regression analysis was conducted using both continuous and binary variables. The results showed no effect in terms of the continuous variables, but higher preoperative D‑dimer levels were significantly associated with a higher 5‑year overall survival compared with lower preoperative D‑dimer levels in the categorical variables. Therefore, curve fitting was performed, which indicated that the association between D‑dimer level and 5‑year survival rate after radical gastrectomy for cancer showed a U‑shaped curve, with P<0.001, high and low D‑dimer levels both indicated poorer prognosis. A curvilinear correlation was demonstrated between preoperative D‑dimer levels and the 5‑year survival rate following radical gastrectomy for cancer. Subsequently, an inflection point analysis found that the inflection point was located at 100‑200 ng/ml. In conclusion, in patients undergoing radical gastrectomy for gastric cancer, preoperative D‑dimer can be used to indicate the current state of the tumor to some extent through blood coagulation status. Notably, a U‑shaped association exists between D‑dimer levels and 5‑year postoperative survival rate in gastric cancer. This association demonstrates varying effects across different intervals. Specifically, D‑dimer levels <100 ng/ml are associated with a worse prognosis, whereas levels >200 ng/ml are associated with a better prognosis.

View Figures

View References

1	Chen S, Zhou D, Yu J, Ruan R, Liu Y, Li Y, Shen Q and Wang S: A novelly developed bipolar needle knife can be an alternative device choice for endoscopic submucosal dissection (with video). Front Med (Lausanne). 9:8886352022. View Article : Google Scholar : PubMed/NCBI
2	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI
3	Li D, Wang R, Wu N and Yu Y: LncRNA HULC as a potential predictor of prognosis and clinicopathological features in patients with digestive system tumors: A meta-analysis. Aging (Albany NY). 14:1797–811. 2022. View Article : Google Scholar : PubMed/NCBI
4	Liu T, Song C, Zhang Y, Siyin ST, Zhang Q, Song M, Cao L and Shi H: Hepatitis B virus infection and the risk of gastrointestinal cancers among Chinese population: A prospective cohort study. Int J Cancer. 150:1018–1028. 2022. View Article : Google Scholar : PubMed/NCBI
5	Wang R, Lai Q, Tang L, Tao Y, Yao Y, Liu Y, Lu Y, Shen C, Lu R, Fan C, et al: A novel 5T4-targeting antibody-drug conjugate H6-DM4 exhibits potent therapeutic efficacy in gastrointestinal tumor xenograft models. Am J Cancer Res. 8:610–623. 2018.PubMed/NCBI
6	Ji J, Wang Z, Sun W, Li Z, Cai H, Zhao E and Gui H: Effects of cynaroside on cell proliferation, apoptosis, migration and invasion though the MET/AKT/mTOR axis in gastric cancer. Int J Mol Sci. 22:121252021. View Article : Google Scholar : PubMed/NCBI
7	You X, Wu J, Zhao X, Jiang X, Tao W, Chen Z, Huang C, Zheng T and Shen X: Fibroblastic galectin-1-fostered invasion and metastasis are mediated by TGF-β1-induced epithelial-mesenchymal transition in gastric cancer. Aging (Albany NY). 13:18464–18481. 2021. View Article : Google Scholar : PubMed/NCBI
8	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
9	Seidlitz T, Chen YT, Uhlemann H, Schölch S, Kochall S, Merker SR, Klimova A, Hennig A, Schweitzer C, Pape K, et al: Mouse models of human gastric cancer subtypes with stomach-specific CreERT2-mediated pathway alterations. Gastroenterology. 157:1599–1614.e2. 2019. View Article : Google Scholar : PubMed/NCBI
10	Lyons K, Le LC, Pham YTH, Borron C, Park JY, Tran CTD, Tran TV, Tran HT, Vu KT, Do CD, et al: Gastric cancer: epidemiology, biology, and prevention: A mini review. Eur J Cancer Prev. 28:397–412. 2019. View Article : Google Scholar : PubMed/NCBI
11	Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D and Bray F: Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012. Eur J Cancer. 49:1374–1403. 2013. View Article : Google Scholar : PubMed/NCBI
12	Yao Y, Sun S, Gu J, Ni H, Zhong K, Xu Q, Zhou D, Wang X, Gao L and Zhu X: Roux-en-Y reconstruction alleviates radical gastrectomy-induced colitis via down-regulation of the butyrate/NLRP3 signaling pathway. EBioMedicine. 86:1043472022. View Article : Google Scholar : PubMed/NCBI
13	Lee SD, Yu D, Lee DY, Shin HS, Jo JH and Lee YC: Upregulated microRNA-193a-3p is responsible for cisplatin resistance in CD44(+) gastric cancer cells. Cancer Sci. 110:662–673. 2019. View Article : Google Scholar : PubMed/NCBI
14	Kim SH, Jin H, Meng RY, Kim DY, Liu YC, Chai OH, Park BH and Kim SM: Activating Hippo pathway via rassf1 by ursolic acid suppresses the tumorigenesis of gastric cancer. Int J Mol Sci. 20:47092019. View Article : Google Scholar : PubMed/NCBI
15	Malloy J, Zhuang D, Kim T, Inskeep P, Kim D and Taylor K: Single and multiple dose evaluation of a novel MetAP2 inhibitor: Results of a randomized, double-blind, placebo-controlled clinical trial. Diabetes Obes Metab. 20:1878–1884. 2018. View Article : Google Scholar : PubMed/NCBI
16	Kamin Mukaz D, Gergi M, Koh I, Zakai NA, Judd SE, Sholzberg M, Baumann Kreuziger L, Freeman K, Colovos C, Olson NC and Cushman M: Thrombo-inflammatory biomarkers and D-dimer in a biracial cohort study. Res Pract Thromb Haemost. 5:e126322021. View Article : Google Scholar : PubMed/NCBI
17	Ho-Tin-Noé B, Goerge T and Wagner DD: Platelets: Guardians of tumor vasculature. Cancer Res. 69:5623–6526. 2009. View Article : Google Scholar : PubMed/NCBI
18	Elyamany G, Alzahrani AM and Bukhary E: Cancer-associated thrombosis: An overview. Clin Med Insights Oncol. 8:129–137. 2014. View Article : Google Scholar : PubMed/NCBI
19	Rickles FR and Falanga A: Activation of clotting factors in cancer. Cancer Treat Res. 148:31–41. 2009. View Article : Google Scholar : PubMed/NCBI
20	Demers M, Krause DS, Schatzberg D, Martinod K, Voorhees JR, Fuchs TA, Scadden DT and Wagner DD: Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci USA. 109:13076–13081. 2012. View Article : Google Scholar : PubMed/NCBI
21	Fukumoto K, Taniguchi T, Usami N, Kawaguchi K, Fukui T, Ishiguro F, Nakamura S and Yokoi K: Preoperative plasma D-dimer level is an independent prognostic factor in patients with completely resected non-small cell lung cancer. Surg Today. 45:63–37. 2015. View Article : Google Scholar : PubMed/NCBI
22	Liu L, Zhang X, Yan B, Gu Q, Zhang X, Jiao J, Sun D, Wang N and Yue X: Elevated plasma D-dimer levels correlate with long term survival of gastric cancer patients. PLoS One. 9:e905472014. View Article : Google Scholar : PubMed/NCBI
23	Guan Y, Xu B, Sui Y, Chen Z, Luan Y, Jiang Y, Wei L, Long W, Zhao S, Han L, et al: Pan-cancer analysis and validation reveals that D-dimer-related genes are prognostic and downregulate CD8⁺ T cells via TGF-beta signaling in gastric cancer. Front Mol Biosci. 9:7907062022. View Article : Google Scholar : PubMed/NCBI
24	Dai H, Zhou H, Sun Y, Xu Z, Wang S, Feng T and Zhang P: D-dimer as a potential clinical marker for predicting metastasis and progression in cancer. Biomed Rep. 9:453–457. 2018.PubMed/NCBI
25	Suzuki T, Shimada H, Nanami T, Oshima Y, Yajima S, Ito M, Washizawa N and Kaneko H: Hyperfibrinogenemia is associated with inflammatory mediators and poor prognosis in patients with gastric cancer. Surg Today. 46:1394–1401. 2016. View Article : Google Scholar : PubMed/NCBI
26	Go SI, Lee MJ, Lee WS, Choi HJ, Lee US, Kim RB, Kang MH, Kim HG, Lee GW, Kang JH, et al: D-dimer can serve as a prognostic and predictive biomarker for metastatic gastric cancer treated by chemotherapy. Medicine (Baltimore). 94:e9512015. View Article : Google Scholar : PubMed/NCBI
27	Kim EY and Song KY: Prognostic value of D-dimer levels in patients with gastric cancer undergoing gastrectomy. Surg Oncol. 37:1015702021. View Article : Google Scholar : PubMed/NCBI
28	Liang Y, He D, Wu L, Ding X, Wang X, Wang B, Zhang R and Liang H: Elevated preoperative plasma D-dimer dose not adversely affect survival of gastric cancer after gastrectomy with curative intent: A propensity score analysis. Chin J Cancer Res. 30:254–262. 2018. View Article : Google Scholar : PubMed/NCBI
29	Edge SB and Compton CC: The american joint committee on cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
30	Coccolini F, Montori G, Ceresoli M, Cima S, Valli MC, Nita GE, Heyer A, Catena F and Ansaloni L: Advanced gastric cancer: What we know and what we still have to learn. World J Gastroenterol. 22:1139–1159. 2016. View Article : Google Scholar : PubMed/NCBI
31	Shen L, Huang Y, Sun M, Xu H, Wei W and Wu W: Clinicopathological features associated with lymph node metastasis in early gastric cancer: Analysis of a single-institution experience in China. Can J Gastroenterol. 23:353–356. 2009. View Article : Google Scholar : PubMed/NCBI
32	Asakawa Y, Ohtaka M, Maekawa S, Fukasawa M, Nakayama Y, Yamaguchi T, Inoue T, Uetake T, Sakamoto M, Sato T, et al: Stratifying the risk of lymph node metastasis in undifferentiated-type early gastric cancer. World J Gastroenterol. 21:2683–2692. 2015. View Article : Google Scholar : PubMed/NCBI