Fibrinogen is one of the key proteins that participate in the protein corona composition of many types of nanoparticles (NPs), and its conformational changes are crucial for activation of immune systems. Recently, we demonstrated that the fibrinogen highly contributed in the protein corona composition at the surface of zeolite nanoparticles. Therefore, understanding the interaction of fibrinogen with zeolite nanoparticles in more details could shed light of their safe applications in medicine. Thus, we probed the molecular interactions between fibrinogen and zeolite nanoparticles using both experimental and simulation approaches. The results indicated that fibrinogen has a strong and thermodynamically favorable interaction with zeolite nanoparticles in a non-cooperative manner. Additionally, fibrinogen experienced a substantial conformational change in the presence of zeolite nanoparticles through a concentration-dependent manner. Simulation results showed that both E- and D-domain of fibrinogen are bound to the EMT zeolite NPs via strong electrostatic interactions, and undergo structural changes leading to exposing normally buried sequences. D-domain has more contribution in this interaction and the C-terminus of γ chain (γ377-394), located in D-domain, showed the highest level of exposure compared to other sequences/residues.

Major depressive disorder (MDD) presumably includes heterogeneous subgroups with differing pathologies. To obtain a marker reflecting such a subgroup, we analyzed the cerebrospinal fluid (CSF) levels of fibrinogen, which has been reported to be elevated in the plasma of patients with MDD. Three fibrinogen-related proteins were measured using aptamer-based analyses and CSF samples of 30 patients with MDD and 30 controls. The numbers of patients with an excessively high level (>99 percentile of the controls) was significantly increased (17 to 23%). Measurement reproducibility of these results was confirmed by an ELISA for fibrinogen (Pearson's r = 0.77). In an independent sample set from 36 patients and 30 controls, using the ELISA, results were similar (22%). When these two sample sets were combined, the number of patients with a high fibrinogen level was significantly increased (15/66; odds ratio 8.53; 95% confidence interval 1.9-39.1, p = 0.0011). By using diffusion tensor imaging, we found white matter tracts abnormalities in patients with a high fibrinogen level but not those patients with a normal fibrinogen level, compared with controls. Plasma fibrinogen levels were similar among the diagnostic groups. Our results point to a subgroup of MDD represented by increased CSF fibrinogen and white matter tract abnormalities.

Non-genetic MMP-2 insufficiency is a relatively unexplored condition which could be induced by pathological overexpression of endogenous MMP-2 inhibitors such as TIMPs and/or the acute phase reactant alpha-2-macroglobulin. Here, we investigate the hypothesis that human fibrinogen (FBG) - an acute phase reactant - inhibits human MMP-2. Following an unexpected observation where sera from human donors including arthritis patients with increased levels of serum FBG exhibited reduced binding of serum proMMP-2 to gelatin, we found that human FBG (0 to 3.6 mg/mL i.e., 0 to 10.6 μM) concentration-dependently inhibited human proMMP-2 and MMP2 from binding to gelatin. Moreover, at normal physiological concentrations, FBG (5.29-11.8 μM) concentration-dependently inhibited (40-70% inhibition) the cleavage of fluorescein-conjugated gelatin by MMP-2, but not MMP-9. Indicative of a mixed-type (combination of competitive and non-competitive) inhibition mechanism, FBG reduced the Vmax (24.9 ± 0.7 min-1 to 17.7 ± 0.9 min-1, P < 0.05) and increased the Michaelis-Menten constant KM (204 ± 6 nM to 478 ± 50 nM, P < 0.05) for the reaction of MMP-2 cleavage of fluorescein-conjugated gelatin. In silico analyses and studies of FBG neutralization with anti-FBG antibodies implicated the domains D and E of FBG in the inhibition of MMP-2. In conclusion, FBG is a natural selective MMP-2 inhibitor, whose pathological elevation could lead to MMP-2 insufficiency in humans.

To identify circulating proteins predictive of acute cardiovascular disease events in the general population, we performed a proteomic screen in plasma from asymptomatic individuals. A "Discovery cohort" of 25 individuals who subsequently incurred a cardiovascular event within 3 years (median age = 70 years, 80% male) was matched to 25 controls remaining event-free for > 5 years (median age = 72 years, 80% male). Plasma proteins were assessed by data independent acquisition mass spectrometry (DIA-MS). Associations with cardiovascular events were tested using Cox regression, adjusted for the New Zealand Cardiovascular Risk Score. Concentrations of leading protein candidates were subsequently measured with ELISAs in a larger (n = 151) independent subset. In the Discovery cohort, 76 plasma proteins were robustly quantified by DIA-MS, with 8 independently associated with cardiovascular events. These included (HR = hazard ratio [95% confidence interval] above vs below median): fibrinogen alpha chain (HR = 1.84 [1.19-2.84]); alpha-2-HS-glycoprotein (also called fetuin A) (HR = 1.86 [1.19-2.93]); clusterin isoform 2 (HR = 1.59 [1.06-2.38]); fibrinogen beta chain (HR = 1.55 [1.04-2.30]); hemoglobin subunit beta (HR = 1.49 [1.04-2.15]); complement component C9 (HR = 1.62 [1.01-2.59]), fibronectin isoform 3 (HR = 0.60 [0.37-0.99]); and lipopolysaccharide-binding protein (HR = 1.58 [1.00-2.49]). The proteins for which DIA-MS and ELISA data were correlated, fibrinogen and hemoglobin, were analyzed in an Extended cohort, with broader inclusion criteria and longer time to events, in which these two proteins were not associated with incident cardiovascular events. We have identified eight candidate proteins that may independently predict cardiovascular events occurring within three years in asymptomatic, low-to-moderate risk individuals, although these appear not to predict events beyond three years.

Wound healing is a complex process and rapid healing necessitates a proper micro-environment. Therefore, design and fabrication of an efficacious wound dressing is an impressive innovation in the field of wound healing. The fabricated wound dressing in this scenario was designed using a combination of the appropriate coagulating and anti-bacterial materials like fibrinogen (as coagulating agent), nisin (as anti-bacterial agent), ethylenediaminetetraacetic acid (as anti-bacterial agent), and alginate (as wound healing agent). Biophysical characterization showed that the interaction of fibrinogen and alginate was associated with minor changes in the secondary structure of the protein. Conformational studies showed that the protein was structurally stable at 42 °C, is the maximum temperature of the infected wound. The properties of the hydrogel such as swelling, mechanical resistance, nisin release, antibacterial activity, cytotoxicity, gel porosity, and blood coagulation were assessed. The results showed a slow release for the nisin during 48 h. Antibacterial studies showed an inhibitory effect on the growth of Gram-negative and Gram-positive bacteria. The hydrogel was also capable to absorb a considerable amount of water and provide oxygenation as well as incorporation of the drug into its structure due to its sufficient porosity. Scanning electron microscopy showed pore sizes of about 14-198 µm in the hydrogel. Cell viability studies indicated high biocompatibility of the hydrogel. Blood coagulation test also confirmed the effectiveness of the synthesized hydrogel in accelerating the process of blood clot formation. In vivo studies showed higher rates of wound healing, re-epithelialization, and collagen deposition. According to the findings from in vitro as well as in vivo studies, the designed hydrogel can be considered as a novel attractive wound dressing after further prerequisite assessments.

The surface of nanoparticles (NPs) get coated by a wide range of biomolecules, upon exposure to biological fluids. It is now being increasingly accepted that NPs with particular physiochemical properties have a capacity to induce conformational changes to proteins and therefore influence their biological fates, we hypothesized that the gold NP's metal surface may also be involved in the observed Fg unfolding and inflammatory response. To mechanistically test this hypothesis, we probed the interaction of Fg with gold surfaces using molecular dynamic simulation (MD) and revealed that the gold surface has a capacity to induce Fg conformational changes in favor of inflammation response. As the integrity of coatings at the surface of ultra-small gold NPs are not thorough, we also hypothesized that the ultra-small gold NPs have a capacity to induce unfolding of Fg regardless of the composition and surface charge of their coatings. Using different surface coatings at the surface of ultra-small gold NPs, we validated this hypothesis. Our findings suggest that gold NPs may cause unforeseen inflammatory effects, as their surface coatings may be degraded by physiological activity.

Fibrinogen-related lectins are carbohydrate-binding proteins of the innate immune system that recognize glycan structures on microbial surfaces. These innate immune lectins are crucial for invertebrates as they do not rely on adaptive immunity for pathogen clearance. Here, we characterize a recombinant fibrinogen-related lectin PmFREP from the black tiger shrimp Penaeus monodon expressed in the Trichoplusia ni insect cell. Electron microscopy and cross-linking experiments revealed that PmFREP is a disulfide-linked dimer of pentamers distinct from other fibrinogen-related lectins. The full-length protein binds N-acetyl sugars in a Ca2+ ion-independent manner. PmFREP recognized and agglutinated Pseudomonas aeruginosa. Weak binding was detected with other bacteria, including Vibrio parahaemolyticus, but no agglutination activity was observed. The biologically active PmFREP will not only be a crucial tool to elucidate the innate immune signaling in P. monodon and other economically important species, but will also aid in detection and prevention of shrimp bacterial infectious diseases.

The supply of oxygen and nutrients and the disposal of metabolic waste in the organs depend strongly on how blood, especially red blood cells, flow through the microvascular network. Macromolecular plasma proteins such as fibrinogen cause red blood cells to form large aggregates, called rouleaux, which are usually assumed to be disaggregated in the circulation due to the shear forces present in bulk flow. This leads to the assumption that rouleaux formation is only relevant in the venule network and in arterioles at low shear rates or stasis. Thanks to an excellent agreement between combined experimental and numerical approaches, we show that despite the large shear rates present in microcapillaries, the presence of either fibrinogen or the synthetic polymer dextran leads to an enhanced formation of robust clusters of red blood cells, even at haematocrits as low as 1%. Robust aggregates are shown to exist in microcapillaries even for fibrinogen concentrations within the healthy physiological range. These persistent aggregates should strongly affect cell distribution and blood perfusion in the microvasculature, with putative implications for blood disorders even within apparently asymptomatic subjects.

Plasma fibrinogen predicts cardiovascular and nonvascular mortality. However, there is limited population-based evidence on the association between fibrinogen levels and dietary intakes of micronutrients possibly associated with inflammation status. Data were taken from the ENRICA study, conducted with 10,808 individuals representative of the population of Spain aged ≥ 18 years. Nutrient intake (vitamin A, carotenoids, vitamin B6, vitamin C, vitamin D, vitamin E, magnesium, selenium, zinc and iron) was estimated with a validated diet history, and plasma fibrinogen was measured under appropriate quality checks. Statistical analyses were performed with linear regression and adjusted for main confounders. The geometric means of fibrinogen (g/L) across increasing quintiles of nutrient intake were 3.22, 3.22, 3.22, 3.16, and 3.19 (p-trend = 0.030) for vitamin E; 3.23, 3.22, 3.20, 3.19, and 3.19 (p-trend = 0.047) for magnesium; and 3.24, 3.22, 3.19, 3.21, and 3.19 (p-trend = 0.050) for iron. These inverse associations were more marked in participants with abdominal obesity and aged ≥ 60 years, but lost statistical significance after adjustment for other nutrients. Although dietary intakes of vitamin E, magnesium and iron were inversely associated with fibrinogen levels, clinical implications of these findings are uncertain since these results were of very small magnitude and mostly explained by intake levels of other nutrients.

Propionibacterium acnes (P. acnes) is a major skin-associated bacterium that was long considered commensal, until several studies revealed it to be an opportunistic pathogen. We investigated the ability of P. acnes surface proteins to recognize ECM proteins and showed that a 58 kDa P. acnes surface protein was specifically recognized by human fibrinogen (hFg). The 58 kDa protein was further characterized by two-dimensional (2-D) electrophoresis and MALDI-ToF as a P. acnes host cell-surface attachment protein, PA25957, recognizing dermatan sulfate (DsA1). This protein sequence contains 432 amino acids with the presence of three structurally different domains: an N-terminal signal peptide, a C-terminal LPXTG motif, and a PT repeat region. DsA1 is mostly produced during stationary phase. It appears to be highly glycosylated, containing GalNAc residues. Purified DsA1 strongly recognizes the Aα and Bβ subunits of hFg, and specific enzymatic deglycosylation of hFg demonstrated the involvement of the protein backbone in the recognition process. The Bβ subunit of hFg was cloned in four peptide fractions (Fg1-Fg4). The N-terminal Fg1 peptide of hFg was recognized by DsA1, and priming DsA1 with Fg1 inhibited DsA1/hFg recognition. We describe here for the first time, the characterization of a P. acnes surface glycoprotein recognizing human fibrinogen.

Myasthenia Gravis (MG) is an autoimmune disease associated with severe neuromuscular weakness. Diagnostic confirmation of MG is typically delayed and secured in about 85% and 50% of patients with generalized and ocular MG, respectively with serum antibodies. We have identified a sensitive and specific diagnostic biomarker for various MG serotypes with quantitative proteomics. Serum proteomes of 18 individuals (MG patients, healthy controls (HC), Rheumatoid Arthritis (RA) were quantified in a pilot study and occurrence of high residual fibrinogen was validated by immunoblotting and further investigated by targeted mass spectrometry on the sera of 79 individuals (31 MG of various serotypes, 30 HC, 18 RA). Initial proteomic analysis identified high residual fibrinogen in MG patient sera which was then validated by antibody-based testing. Subsequently, a blinded study of independent samples showed 100% differentiation of MG patients from controls. A final serological quantification of 14 surrogate peptides derived from α-, β-, and γ-subunits of fibrinogen in 79 individuals revealed fibrinogen to be highly specific and 100% sensitive for MG (p < 0.00001), with a remarkable average higher abundance of > 1000-fold over control groups. Our unanticipated discovery of high levels of residual serum fibrinogen in all MG patients can secure rapid bedside diagnosis of MG.

This study aimed to assess the association of coagulation-related indicators such as plasma fibrinogen (FIB), D-dimer, and fibrin degradation product (FDP) in rheumatoid arthritis (RA) with the disease activity. Data from 105 RA patients and 102 age- and gender-matched healthy controls were collected in the retrospective study. Disease activity score in 28 joints based on C-reactive protein (DAS28-CRP) was used to divide RA patients into low activity group (DAS28-CRP ≤ 2.7) and active group (DAS28-CRP > 2.7). Receiver operating characteristic (ROC) curve was applied to determine area under the curve (AUC). The association between plasma FIB, D-dimer, and FDP and DAS28-CRP was evaluated by spearman correlation. Logistical regression analysis was used to identify the independent variables associated with RA disease activity. RA patients showed higher levels of plasma FIB, D-dimer, and FDP than the controls (P < 0.01). Plasma FIB, D-dimer, and FDP were also increased in active groups of RA patients than those in inactive groups (P < 0.001). ROC curve analyses revealed that the AUC of D-dimer was higher than erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF), and that of FDP was higher than RF in RA patients. In addition, the optimal cut-off value of plasma FIB, D-dimer, and FDP for RA diagnosis was 286 mg/dL, 470 μg/L, and 1.45 mg/L, respectively. Spearman analysis showed that plasma FIB, D-dimer, and FDP were positively related with DAS28-CRP (P < 0.001) in RA patients. Logistical regression analysis showed that D-dimer (odds ratio 2.862, 95% confidence interval 1.851-5.426, P < 0.001) was an independent variable associated with RA disease activity. FIB, D-dimer, and FDP were increased in RA patients and positively correlated with the disease activity of RA. D-dimer may act as a novel inflammatory indice for indicating disease activity in RA patients.

Stem cells therapy offers a viable alternative for treatment of bone disorders to the conventional bone grafting. However clinical therapies are still hindered by the insufficient knowledge on the conditions that maximize stem cells differentiation. Hereby, we introduce a novel 3D honeycomb architecture scaffold that strongly support osteogenic differentiation of human adipose derived mesenchymal stem cells (ADMSCs). The scaffold is based on electrospun hybrid nanofibers consisting of poly (L-lactide ε-caprolactone) and fibrinogen (PLCL/FBG). Classical fibers orientations, random or aligned were also produced and studied for comparison. The overall morphology of ADMSC's generally followed the nanofibers orientation and dimensionality developing regular focal adhesions and direction-dependent actin cytoskeleton bundles. However, there was an initial tendency for cells rounding on honeycomb scaffolds before ADMSCs formed a distinct bridging network. This specific cells organization appeared to have significant impact on the differentiation potential of ADMSCs towards osteogenic lineage, as indicated by the alkaline phosphatase production, calcium deposition and specific genes expression. Collectively, it was observed synergistic effect of nanofibers with honeycomb architecture on the behavior of ADMSCs entering osteogenic path of differentiation which outlines the potential benefits from insertion of such bioinspired geometrical cues within scaffolds for bone tissue engineering.

There is mounting evidence that malnutrition and systemic inflammation status are involved in the prognosis of various cancers. In this study, we aimed to evaluate the prognostic value of the pretreatment fibrinogen-albumin ratio index (FARI) in nasopharyngeal carcinoma (NPC) patients receiving definite radiotherapy. NPC patients who received definite radiotherapy between January 2013 and December 2019 were included. A receiver operating characteristic (ROC) curve was used to determine the optimal cutoff value. The clinicopathological characteristics of the patients were compared via the Chi-square test. Survival curves were analyzed by the Kaplan‒Meier method. The prognostic factors were evaluated by univariate and multivariate analyses via Cox hazards regression analysis. A total of 225 patients were enrolled, and the median follow-up time was 48.5 months. High FARI was correlated with worse ECOG score (p = 0.003), higher EBV-DNA titer (p = 0.047), and more advanced clinical stage (p < 0.001). In the multivariable analysis, FARI independently predicted OS (HR 2.399, 95% CI 1.294-4.450, P < 0.001), PFS (HR 2.085, 95% CI 1.200-3.625, P = 0.009), and DMFS (HR 2.527, 95% CI 1.288-4.958, P < 0.001). The current findings suggest that a high pretreatment FARI is an independent predictor of OS, PFS and DMFS in NPC patients undergoing definite radiotherapy.

Perioperative bleeding is a potentially devastating complication in neurosurgical patients, and plasma fibrinogen concentration has been identified as a potential modifiable risk factor for perioperative bleeding. The aim of this study was to evaluate preconditioning with Crotalus atrox venom (Cv-PC) as potential preventive therapy for reducing perioperative hemorrhage in the rodent model of surgical brain injury (SBI). C. atrox venom contains snake venom metalloproteinases that cleave fibrinogen into fibrin split products without inducing clotting. Separately, fibrinogen split products induce fibrinogen production, thereby elevating plasma fibrinogen levels. Thus, the hypothesis was that preconditioning with C. atrox venom will produce fibrinogen spilt products, thereby upregulating fibrinogen levels, ultimately improving perioperative hemostasis during SBI. We observed that Cv-PC SBI animals had significantly reduced intraoperative hemorrhage and postoperative hematoma volumes compared to those of vehicle preconditioned SBI animals. Cv-PC animals were also found to have higher levels of plasma fibrinogen at the time of surgery, with unchanged prothrombin time. Cv-PC studies with fractions of C. atrox venom suggest that snake venom metalloproteinases are largely responsible for the improved hemostasis by Cv-PC. Our findings indicate that Cv-PC increases plasma fibrinogen levels and may provide a promising therapy for reducing perioperative hemorrhage in elective surgeries.

This study investigated changes in coagulation and associations with occurrence of bleeding and thrombosis during extracorporeal membrane oxygenation (ECMO) therapy. The study included 100 adult ECMO-patients. Standard coagulation parameters, platelet aggregation and thromboelastometry (ROTEM®) were compared with healthy controls. Data on bleeding and thrombosis were collected until recovery or death. Mortality data were collected 30 days after weaning from ECMO. During ECMO therapy, 53 patients experienced at least one moderate or major bleed. Among these, 42 (79%) patients experienced the first bleeding on day 1 or 2. Platelet aggregation and ROTEM® revealed a hypocoagulable state in ECMO patients when compared with healthy controls. Patients bleeding on day 1 or 2, had lower platelet count (p = 0.04), poorer platelet aggregation and lower levels of fibrinogen (p < 0.01) than patients not bleeding on day 1 or 2. Further, ROTEM® clot propagation was reduced in bleeding patients (p < 0.001). Mortality was higher among bleeding patients than patients not bleeding on day 1 or 2 (67% versus 34%, p < 0.01). Congruity existed between ROTEM® measurements and standard coagulation assays, but plasma fibrinogen had a stronger association with bleeding than ROTEM® measurements. The present study does not support ROTEM® analysis as a routine part of coagulation monitoring during ECMO therapy.

Neutrophils are pivotal players in immune defence which includes a process of release of histones and DNA as neutrophil extracellular traps (NETs). Histones, while toxic to invading pathogens, also kill host cells, including neutrophils. Bacteria have evolved mechanisms to escape neutrophils, including the secretion of leucocidins (e.g. ionomycin). Live cell video microscopy showed how fibrinogen and fibrin influence NETosis and neutrophil responses to extracellular histones. Histones were rapidly lethal to neutrophils after binding to cells, but formation of fibrinogen/fibrin-histone aggregates prevented cell death. Histone cytotoxicity was also reduced by citrullination by peptidyl arginine deiminase 4, or digestion by serine proteases. Ionomycin and phorbol 12-myristate 13 acetate (PMA) are used to trigger NETosis. Fibrinogen was responsible for a second distinct mechanism of neutrophil protection after treatment with ionomycin. Fibrinogen clustered on the surface of ionomycin-stimulated neutrophils to delay NETosis; and blocking the β integrin receptor, αMβ2, abolished fibrinogen protection. Fibrinogen did not bind to or protect neutrophils stimulated with PMA. Fibrinogen is an acute phase protein that will protect exposed cells from damaging circulating histones or leucocidins; but fibrinogen depletion/consumption, as in trauma or sepsis will reduce protection. It is necessary to consider the role of fibrinogen in NETosis.

Previous work has suggested that ischemic stroke (IS) may be more likely to occur in individuals with a genetic predisposition. In this study, we investigated the potential association of IS-relevant genetic risk factors with cardioembolic stroke (CES) in atrial fibrillation (AF) patients with low CHA2DS2-VaSc score. Genotyping was performed using the GenomeLab SNPstream genotyping platform for five IS-relevant SNPs (MMP-9 C1562T, ALOX5AP SG13S114A/T, MTHFR 677 C/T, FGB 455 G/A, and eNOS G298A) in 479 AF patients with CES and 580 age and sex-matched AF patients without CES. The multivariate analysis adjusted for potential confounders and demonstrated that FGB 455 G/A was independently associated with increased risk of CES in AF patients and the significance remained after Bonferroni correction in the additive, dominant, and recessive models with ORs of 1.548 (95% CI: 1.251-1.915, P = 0.001), 1.588 (95% CI: (1.226-2.057, P = 0.003), and 2.394 (95% CI: 1.357-4.223, P = 0.015), respectively. Plasma fibrinogen levels were significantly higher in patients with the A allele compared with patients with genotype of GG (3.29 ± 0.38 mg/dl vs. 2.87 ± 0.18 mg/dl, P < 0.001). We found for the first time that the A allele of FGB 455 G/A was a risk factor for CES in AF patients, probably by elevating the level of plasma fibrinogen.

Research suggests that fibrinogen was related to diabetic retinopathy (DR). Then, the relationship between functional indices of fibrinogen and detailed staging of DR has not been explored. Type 2 diabetic and healthy control subjects (n = 960) were recruited in a cross-sectional study. Participants with type 2 diabetes mellitus were categorized into five stages according to their fundus lesions, and fibrinogen (Fib) and its functional indices (angle α and k value) were measured. The angle α levels increased in diabetic subjects with retinopathy compared with those without, and it was significantly elevated early in retinopathy. In contrast, the k value levels slightly decreased. Despite observing an increase in angle α levels and a decrease in k value levels during the later stages of retinopathy compared to the earlier stages, there was no statistically significant difference in the later stages. The association of the angle α and k value with DR was independent of the hyperglycaemic state and other potential confounders (OR = 1.672, 95% CI 1.489-1.876, P < 0.01; OR = 0.013, 95% CI 0.004-0.041, P < 0.01). The angle α levels and k value levels were closely correlated with retinopathy (r = 0.593, P < 0.00; r = - 0.646, P < 0.01). The ROC curve indicated that the diagnostic value of angle α and k value were (AUC = 0.897, P < 0.001; AUC = 0.859, P < 0.001). Fibrinogen function indexes, such as angle α and k value, may be valuable for the early diagnosis of DR but do not directly assess the severity of DR.

Hyperfibrinogenemia and cancer-associated systemic inflammatory response are strongly associated with cancer progression and prognosis. We aimed to develop a novel prognostic score (F-SII score) on the basis of preoperative fibrinogen (F) and systemic immunoinflammatory index (SII), and evaluate its predictive value in patients with resectable gastric cancer (GC). Patients diagnosed with GC between January 2012 and December 2016 were reviewed. The F-SII score was 2 for patients with a high fibrinogen level (≥ 3.37 g/L) and a high SII (≥ 372.8), whereas that for patients with one or neither was 1 or 0, respectively. A high F-SII score was significantly associated with older patient age, a high ASA score, large tumor size, large proportion of perineural invasion, and late TNM stage. Multivariate analysis indicated that the F-SII score, histological grade, and TNM stage were independent factors for overall survival (OS). The Harrell's concordance index (C-index) of a nomogram based on the F-SII score and several clinicopathological manifestations was 0.72, which showed a better predictive ability for OS than the TNM stage alone (0.68). In conclusion, preoperative F-SII may serve as a useful predictive factor for OS and refine outcome prediction for patients with resectable GC combined with traditional clinicopathological analysis.