Abstract
Background
The fibrinogen to albumin ratio (FAR) is increasingly regarded as a potential biomarker for predicting prognosis in variety of malignant tumors, but not in gastric signet ring cell carcinoma (GSRC). This study seeks to examine the prognostic value of the FAR and explore a novel FAR-CA125 score (FCS) in resectable GSRC patients.
Methods
A retrospective cohort was conducted including 330 GSRC patients who underwent curative resection. Kaplan–Meier (K–M) and Cox regression were used to analysis the prognostic value of FAR and FCS. And a predictive nomogram model was developed.
Results
The optimal cut-off values for CA125 and FAR were 9.88 and 0.0697, respectively, according to the receiver operating characteristic curve (ROC). Th area under the ROC curve of FCS is higher than CA125 and FAR. 330 patients were grouped into three groups according to the FCS. High FCS was related to males, anemia, tumor size, TNM stage, lymph node metastasis, tumor invasion depth, SII, and pathological subtypes. K–M analysis showed that high FCS and FAR were associated with poor survival. In the multivariate analysis, FCS, TNM stage, and SII were independent prognostic factors for poor OS in resectable GSRC patients. And the predictive accuracy of clinical nomogram contained FCS was better than TNM stage.
Conclusion
This study indicated that the FCS is a prognostic, and effective biomarker for patients with surgically resectable GSRC. Such developed FCS-based nomogram could be effective tools to assist the clinicians to determine the treatment strategy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Availability of data and material
The data that support the findings of this study are available on request from the corresponding author, upon reasonable request.
References
An Q, Liu W, Yang Y, Yang B (2020) Preoperative fibrinogen-to-albumin ratio, a potential prognostic factor for patients with stage IB-IIA cervical cancer. BMC Cancer 20:691. https://doi.org/10.1186/s12885-020-07191-8
Comamala M et al (2011) Downregulation of cell surface CA125/MUC16 induces epithelial-to-mesenchymal transition and restores EGFR signalling in NIH:OVCAR3 ovarian carcinoma cells. Br J Cancer 104:989–999. https://doi.org/10.1038/bjc.2011.34
Echizen K, Hirose O, Maeda Y, Oshima M (2016) Inflammation in gastric cancer: interplay of the COX-2/prostaglandin E2 and Toll-like receptor/MyD88 pathways. Cancer Sci 107:391–397. https://doi.org/10.1111/cas.12901
Fan Z et al (2019) The CRP/albumin ratio predicts survival and monitors chemotherapeutic effectiveness in patients with advanced pancreatic cancer. Cancer Manag Res 11:8781–8788. https://doi.org/10.2147/CMAR.S211363
Fléjou JF (2011) WHO Classification of digestive tumors: the fourth edition. Ann Pathol 31:S27-31. https://doi.org/10.1016/j.annpat.2011.08.001
Guo W et al (2019) Systemic immune-inflammation index (SII) is useful to predict survival outcomes in patients with surgically resected non-small cell lung cancer. Thorac Cancer 10:761–768. https://doi.org/10.1111/1759-7714.12995
Higaki E et al (2016) Gene copy number gain of EGFR is a poor prognostic biomarker in gastric cancer: evaluation of 855 patients with bright-field dual in situ hybridization (DISH) method. Gastric Cancer 19:63–73. https://doi.org/10.1007/s10120-014-0449-9
Hong S et al (2015) The prognostic nutritional index (PNI) predicts overall survival of small-cell lung cancer patients. Tumour Biol 36:3389–3397. https://doi.org/10.1007/s13277-014-2973-y
Hunt RH et al (2015) The stomach in health and disease. Gut 64:1650–1668. https://doi.org/10.1136/gutjnl-2014-307595
Hwang KT et al (2017) Prognostic influence of preoperative fibrinogen to albumin ratio for breast cancer. J Breast Cancer 20:254–263. https://doi.org/10.4048/jbc.2017.20.3.254
Jenkins DR, Craner MJ, Esiri MM, DeLuca GC (2018) Contribution of fibrinogen to inflammation and neuronal density in human traumatic brain injury. J Neurotrauma 35:2259–2271. https://doi.org/10.1089/neu.2017.5291
Keller U (2019) Nutritional laboratory markers in malnutrition. J Clin Med. https://doi.org/10.3390/jcm8060775
Kim YH et al (2017) Histologic purity of signet ring cell carcinoma is a favorable risk factor for lymph node metastasis in poorly cohesive, submucosa-invasive early gastric carcinoma. Gastric Cancer 20:583–590. https://doi.org/10.1007/s10120-016-0645-x
Lee HS et al (2007) Protein expression profiling and molecular classification of gastric cancer by the tissue array method. Clin Cancer Res 13:4154–4163. https://doi.org/10.1158/1078-0432.CCR-07-0173
Liang Y et al (2018) Prognostic value of the fibrinogen/albumin ratio (FAR) in patients with operable soft tissue sarcoma. BMC Cancer 18:942. https://doi.org/10.1186/s12885-018-4856-x
Luo Y, Kim HS, Kim M, Lee M, Song YS (2017) Elevated plasma fibrinogen levels and prognosis of epithelial ovarian cancer: a cohort study and meta-analysis. J Gynecol Oncol 28:e36. https://doi.org/10.3802/jgo.2017.28.e36
Luyendyk JP, Schoenecker JG, Flick MJ (2019) The multifaceted role of fibrinogen in tissue injury and inflammation. Blood 133:511–520. https://doi.org/10.1182/blood-2018-07-818211
Meyer AR, Goldenring JR (2018) Injury, repair, inflammation and metaplasia in the stomach. J Physiol 596:3861–3867. https://doi.org/10.1113/JP275512
Nagtegaal ID et al (2020) The 2019 WHO classification of tumours of the digestive system. Histopathology 76:182–188. https://doi.org/10.1111/his.13975
Nitsche U et al (2013) Mucinous and signet-ring cell colorectal cancers differ from classical adenocarcinomas in tumor biology and prognosis. Ann Surg 258:775–782. https://doi.org/10.1097/SLA.0b013e3182a69f7e. (discussion 782-783)
Ocana A, Nieto-Jiménez C, Pandiella A, Templeton AJ (2017) Neutrophils in cancer: prognostic role and therapeutic strategies. Mol Cancer 16:137. https://doi.org/10.1186/s12943-017-0707-7
Pernot S, Voron T, Perkins G, Lagorce-Pages C, Berger A, Taieb J (2015) Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge. World J Gastroenterol 21:11428–11438. https://doi.org/10.3748/wjg.v21.i40.11428
Pichler M, Hutterer GC, Stojakovic T, Mannweiler S, Pummer K, Zigeuner R (2013) High plasma fibrinogen level represents an independent negative prognostic factor regarding cancer-specific, metastasis-free, as well as overall survival in a European cohort of non-metastatic renal cell carcinoma patients. Br J Cancer 109:1123–1129. https://doi.org/10.1038/bjc.2013.443
Pokala SK et al (2018) Incidence, survival, and predictors of lymph node involvement in early-stage gastric signet ring cell carcinoma in the US. J Gastrointest Surg 22:569–577. https://doi.org/10.1007/s11605-017-3500-4
Repetto O, De Re V (2017) Coagulation and fibrinolysis in gastric cancer. Ann N Y Acad Sci 1404:27–48. https://doi.org/10.1111/nyas.13454
Rump A, Morikawa Y, Tanaka M, Minami S, Umesaki N, Takeuchi M, Miyajima A (2004) Binding of ovarian cancer antigen CA125/MUC16 to mesothelin mediates cell adhesion. J Biol Chem 279:9190–9198. https://doi.org/10.1074/jbc.M312372200
Seebacher V et al (2019) Factors associated with post-relapse survival in patients with recurrent cervical cancer: the value of the inflammation-based Glasgow Prognostic Score. Arch Gynecol Obstet 299:1055–1062. https://doi.org/10.1007/s00404-018-4993-0
Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F (2020) Gastric cancer. Lancet 396:635–648. https://doi.org/10.1016/S0140-6736(20)31288-5
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660
Taghavi S, Jayarajan SN, Davey A, Willis AI (2012) Prognostic significance of signet ring gastric cancer. J Clin Oncol 30:3493–3498. https://doi.org/10.1200/JCO.2012.42.6635
Tang L, Liu K, Wang J, Wang C, Zhao P, Liu J (2010) High preoperative plasma fibrinogen levels are associated with distant metastases and impaired prognosis after curative resection in patients with colorectal cancer. J Surg Oncol 102:428–432. https://doi.org/10.1002/jso.21668
Tang S et al (2020) The prognostic value of preoperative fibrinogen-to-prealbumin ratio and a novel FFC score in patients with resectable gastric cancer. BMC Cancer 20:382. https://doi.org/10.1186/s12885-020-06866-6
Xie Y, Shi L, He X, Luo Y (2021) Gastrointestinal cancers in China, the USA, and Europe. Gastroenterol Rep (oxf) 9:91–104. https://doi.org/10.1093/gastro/goab010
Xu Q et al (2018) A novel inflammation-based prognostic score: the fibrinogen/albumin ratio predicts prognoses of patients after curative resection for hepatocellular carcinoma. J Immunol Res 2018:4925498. https://doi.org/10.1155/2018/4925498
Yamamoto M et al (2019) Combination of serum albumin and cholinesterase levels as prognostic indicator in patients ith colorectal cancer. Anticancer Res 39:1085–1090. https://doi.org/10.21873/anticanres.13217
Yin BW, Lloyd KO (2001) Molecular cloning of the CA125 ovarian cancer antigen: identification as a new mucin, MUC16. J Biol Chem 276:27371–27375. https://doi.org/10.1074/jbc.M103554200
Zhang J et al (2020) Prognostic value of the combination of CEA and fibrinogen/albumin ratio in resectable gastric cancer. Cancer Manag Res 12:2767–2775. https://doi.org/10.2147/CMAR.S246566
Zhao B, Zhang J, Zhang J, Luo R, Wang Z, Xu H, Huang B (2018) Assessment of the 8th edition of TNM staging system for gastric cancer: the results from the SEER and a single-institution database. Future Oncol 14:3023–3035. https://doi.org/10.2217/fon-2018-0299
Zheng HC, Li XH, Hara T, Masuda S, Yang XH, Guan YF, Takano Y (2008) Mixed-type gastric carcinomas exhibit more aggressive features and indicate the histogenesis of carcinomas. Virchows Arch 452:525–534. https://doi.org/10.1007/s00428-007-0572-7
Zhou H, Dong A, Xia H, He G, Cui J (2018) Associations between CA19-9 and CA125 levels and human epidermal growth factor receptor 2 overexpression in patients with gastric cancer. Oncol Lett 16:1079–1086. https://doi.org/10.3892/ol.2018.8731
Funding
None.
Author information
Authors and Affiliations
Contributions
Conception and design of the work: YMS; acquisition, analysis, interpretation of the data, drafting of manuscript: YYL, ZW, WX, WJW, XC. All authors approved the final version of the paper.
Corresponding author
Ethics declarations
Conflicts of interest
The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Institutional review board statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Ethics Committee of Lanzhou University Second Hospital (2022A-214).
Informed consent statement
In this retrospective study, informed consent was not necessary as all patients were anonymized.
Consent for publication
Not applicable.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Shen, Y., Li, Y., Wang, Z. et al. The prognostic value of FAR and a novel FAR-CA125 score in resectable gastric signet ring cell carcinoma patients. J Cancer Res Clin Oncol 149, 9597–9608 (2023). https://doi.org/10.1007/s00432-023-04870-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-023-04870-4