Shen Q, Sun ZH, Xu YM, Hu QB, Zhang WH, Huang SA. Associations between complete-blood-count-derived inflammatory markers and gastric ulcer: A cross-sectional study. World J Gastroenterol 2025; 31(38): 111298 [DOI: 10.3748/wjg.v31.i38.111298]
Corresponding Author of This Article
Shen-An Huang, MD, Doctor, Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Donghu District, Nanchang 330006, Jiangxi Province, China. 4417760@qq.com
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Qi Shen, Qi-Bo Hu, Shen-An Huang, Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Zhong-Hua Sun, Wen-Hong Zhang, Medical School of Nanjing University, Nanjing 210093, Jiangsu Province, China
Ya-Meng Xu, Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu Province, China
Co-corresponding authors: Wen-Hong Zhang and Shen-An Huang.
Author contributions: Shen Q contributed to data acquisition and processing, and manuscript drafting; Sun ZH contributed to data statistical analysis and critical revision of the manuscript; Xu YM contributed to technique assistance and statistical analysis; Hu QB contributed to revising the manuscript; Zhang WH contributed to research design and critical revision of the manuscript; Huang SA contributed to research design, results interpretation, and critical revision of the manuscript; All authors have read and approve the final manuscript.
Institutional review board statement: This study was approved by the Ethics Committee of the Second Affiliated Hospital of Nanchang University (No. O-MedResEthics2025-51).
Informed consent statement: The informed consent was waived by the Institutional Review Board.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Shen-An Huang, MD, Doctor, Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, No. 1 Min De Road, Donghu District, Nanchang 330006, Jiangxi Province, China. 4417760@qq.com
Received: June 27, 2025 Revised: August 1, 2025 Accepted: September 4, 2025 Published online: October 14, 2025 Processing time: 109 Days and 15.2 Hours
Abstract
BACKGROUND
Gastric ulcer (GU), a common gastrointestinal condition, is influenced by multiple factors, particularly inflammatory and immune responses. Complete blood count (CBC)-derived inflammatory biomarkers represent a novel indicator of systemic inflammation and immune status; however, their association with GU remains unclear.
AIM
To investigate the association between CBC-derived inflammatory markers and GU.
METHODS
The study sample included individuals admitted to the Gastroenterology Unit of the Second Affiliated Hospital of Nanchang University from 2023 to 2024. We explored how each CBC-based inflammation indicator correlated with GU occurrence through logistic models, and assessed their predictive ability using receiver operating characteristic curve analysis. Additionally, we applied the least absolute shrinkage and selection operator method along with stepwise regression techniques to determine which inflammatory indicators were most significantly linked to GU.
RESULTS
Higher levels of log2 neutrophil-to-lymphocyte ratio, log2 monocyte-to-lymphocyte ratio, log2 systemic immune-inflammation index, log2 systemic inflammatory response index (SIRI), and log2 aggregate index of systemic inflammation were significantly associated with increased GU prevalence across all models, while log2 platelet-to-lymphocyte ratio was significant only in the fully adjusted model. SIRI demonstrated the highest discriminative ability, with an area under the curve of 0.868.
CONCLUSION
Hematological indicators derived from CBC tests show a significant correlation with the prevalence of GU. Among them, SIRI demonstrated the most prominent association. These markers could act as practical tools in recognizing individuals more likely to develop GU.
Core Tip: This study investigates the associations between inflammatory biomarkers derived from complete blood count (CBC) and the prevalence of gastric ulcer (GU); a condition closely linked to systemic immune and inflammatory response (SIRI). By applying logistic regression, receiver operating characteristic curve analysis, and rigorous variable selection techniques (least absolute shrinkage and selection operator and stepwise regression), we evaluated six CBC-derived markers. In particular, SIRI was significantly associated with GU prevalence and demonstrated high discriminatory power.
Citation: Shen Q, Sun ZH, Xu YM, Hu QB, Zhang WH, Huang SA. Associations between complete-blood-count-derived inflammatory markers and gastric ulcer: A cross-sectional study. World J Gastroenterol 2025; 31(38): 111298
Gastric ulcer (GU) is a common upper gastrointestinal disease, typically referring to the deep structure of the gastric mucosa eroded by gastric acid and pepsin, resulting in an ulcerative injury with a diameter > 5 mm and penetrating the mucosal muscular layer[1]. GU affects quality of life and can lead to severe complications such as bleeding, perforation, and obstruction. Peptic ulcer disease (PUD), including GU and duodenal ulcer, affects 5%-10% of the global population over a lifetime[2]. Among PUD cases, GUs account for a substantial proportion. In China, the prevalence of GU varies from 2.5% to 6% depending on the population and diagnostic method. For example, a large-scale community study reported a weighted GU prevalence of 2.5% among Chinese adults aged 18-64 years[3], while an endoscopy-based study in Shanghai found 17.2% had peptic ulcer and approximately 6% had GU[4]. These findings underscore the considerable disease burden and highlight the necessity of identifying accessible and low-cost inflammatory biomarkers in Chinese populations.
Inflammation is a crucial factor in the development of GU, and several studies have demonstrated the involvement of inflammation-related signaling pathways and factors. For example, the activation of inflammation-related signaling pathways is associated with the development of GUs, which involves nuclear factor kappa-B-mediated inflammation[5,6]. In addition, the presence of peri-ulcer mucosal inflammation is an independent risk factor for 30-day rebleeding in patients with bleeding GUs. Many substances have been shown to relieve GUs through anti-inflammatory effects. For example, fucoidan reduces GU damage by controlling inflammation[7]. Populin regulates genes associated with inflammation and promotes the healing of GUs[8].
Recently, attention has turned to systemic inflammatory markers derived from peripheral blood cell counts, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI). These biomarkers have been linked to various pathological conditions. For instance, Wang et al[9] reported that elevated values of SII, SIRI, and NLR were significantly related to a greater likelihood of developing metabolic dysfunction-associated steatotic liver disease. Huang et al[10] identified strong positive relationships involving NLR, PLR, SII, SIRI, and AISI in relation to heart failure occurrence. Xu et al[11] suggested that SII may be a particularly sensitive indicator of systemic inflammation in individuals with hypertension. Chen et al[12] reported that SII and PLR were inversely associated with infertility, highlighting their potential relevance to reproductive health. These studies suggest the potential of complete blood count (CBC)-derived inflammatory indices to reflect systemic immune status and predict disease risk across a wide range of health conditions. While several studies have demonstrated associations between certain CBC-derived markers and the prevalence or prognosis of PUD[13-18], the relationship between these novel biomarkers and GU specifically remains underexplored. Furthermore, comparative data across multiple markers are limited.
To fill these research gaps, we implemented a cross-sectional investigation based on a general population sample to explore the relationships between various CBC-derived inflammatory indices and GU prevalence, employing diverse statistical methods to assess and contrast their predictive capacities.
MATERIALS AND METHODS
Study population
This cross-sectional study was conducted between 2023 and 2024 at the Department of Gastroenterology, Second Affiliated Hospital of Nanchang University. All patients who underwent upper gastrointestinal endoscopy during the study period were consecutively screened for eligibility based on predefined inclusion and exclusion criteria. The eligibility requirements included: (1) Individuals aged 18 or above; (2) Those who had completed an upper gastrointestinal endoscopic examination; and (3) Diagnosis of GU confirmed by both gastroscopic and histopathological findings by two independent endoscopy specialists.
Individuals without any endoscopic or pathological evidence of ulcers and who met all exclusion criteria were considered for the control group. The exclusion criteria included other organic gastrointestinal diseases, autoimmune disorders, malignancies, severe hepatic or renal dysfunction, and missing laboratory data.
A total of 253 patients were initially identified, including 172 diagnosed with GU and 81 potential controls. Among them, 10 individuals were excluded due to missing data on serum creatinine or blood urea nitrogen levels. Consequently, 166 GU patients and 77 controls were included in the final analysis. This real-world sampling strategy aimed to reflect actual clinical practice and minimize selection bias (Figure 1). This research was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines for observational studies.
Figure 1 Flowchart for the study.
GU: Gastric ulcer; GI: Gastrointestinal; IBD: Inflammatory bowel disease.
Inflammatory indicators based on CBC
All participants provided fasting venous blood specimens prior to their gastroscopy procedure. Inflammatory indices derived from CBC, such as NLR, MLR, PLR, SIRI, SII, and AISI were computed using data from standard hematological tests[19-23]. NLR was calculated by neutrophil count/Lymphocyte count. MLR was calculated by monocyte count/Lymphocyte count. PLR was calculated by platelet count/Lymphocyte count. SIRI was calculated by neutrophil count × monocyte count/Lymphocyte count. SII was calculated by platelet count × neutrophil count/Lymphocyte count. AISI was calculated by neutrophil count × platelet count × monocyte count/Lymphocyte count.
Covariates
Based on previous studies of GUs and novel inflammatory markers, we selected the following variables as covariates[23]. Data on age, gender, marital status, and health status, including history of hypertension, diabetes, and stroke, were collected using a structured questionnaire. Serum creatinine and blood urea nitrogen levels were determined through laboratory analysis of fasting blood samples collected before endoscopy. The estimated glomerular filtration rate (eGFR) was determined using the 2021 chronic kidney disease epidemiology collaboration equation that relies on serum creatinine, age, and sex, without accounting for race as a variable[24,25]. Within this formula, age is treated as a numeric continuous input, while sex is represented as a dichotomous variable (female = 0, male = 1) to appropriately modify the eGFR estimation.
Statistical analysis
Participants’ baseline characteristics were categorized into GU groups and controls. We evaluated whether continuous variables followed a normal distribution by applying the Shapiro-Wilk test. Continuous variables with normal distribution were analyzed using independent t tests and expressed as mean ± SD. For those not meeting normality assumptions, the Mann-Whitney U test was applied, and results were shown as median with interquartile range (IQR). Categorical data were summarized as counts and percentages, and group differences were examined using the χ2 test.
Six systemic inflammatory markers were analyzed as continuous independent variables and were log-transformed due to their skewed distributions. To assess the association between each CBC-derived inflammatory biomarker and the presence of GU, multivariate logistic regression models were constructed with three tiers of covariate control. Model 1 included no adjustments; model 2 accounted for age, sex, and marital status; and model 3 was comprehensively adjusted for the variables in model 2, in addition to hypertension, diabetes, stroke, serum creatinine, and blood urea nitrogen levels. The predictive ability of these biomarkers for GU was evaluated using receiver operating characteristic (ROC) curve analysis.
Additionally, least absolute shrinkage and selection operator (LASSO) and stepwise regression models (with sle = 0.1 and sls = 0.05) were used to identify the inflammatory markers most strongly associated with GU, with all covariates from the fully adjusted model (model 3) included as candidate variables to control for potential confounding factors. For LASSO, we selected the penalty parameter based on the λ + 1 SE rule to achieve a more parsimonious model while maintaining predictive performance. A two-tailed P < 0.05 was considered statistically significant. All analyses were conducted using R software, v4.2.1 (R Foundation for Statistical Computing).
RESULTS
General characteristics
The demographic and clinical characteristics of the study population are detailed in Table 1, which includes 243 individuals with a median age of 60 years (IQR: 49-70 years). Among all participants, 68.3% were diagnosed with GU, and 63.0% were male. Compared with the control group, patients with GU were older, more likely to be male, and exhibited a higher prevalence of hypertension, diabetes, and stroke, as well as poorer renal function. In addition, levels of NLR, MLR, PLR, SIRI, SII, and AISI were significantly higher in the GU group than in the control group.
Table 1 Characteristics of participants by gastric ulcer status, n (%).
Association between CBC-derived inflammatory biomarkers and prevalence of GU
As shown in Table 2, multivariate logistic regression analysis revealed that the prevalence of GU rose with each log2-unit increment in inflammatory biomarkers derived from CBC. Except for PLR, which was significantly associated with GU only in the fully adjusted model, all other markers (NLR, MLR, SIRI, SII, and AISI) showed significant associations with GU across all models.
Table 2 Results of weighted logistic regression analysis examining the association between complete blood count-derived inflammatory markers and gastric ulcer.
Value of inflammatory biomarkers from CBC in predicting GU
To assess their diagnostic utility, ROC curve analysis was conducted using log2-transformed inflammatory biomarkers derived from CBC to differentiate GU patients from non-GU individuals. The area under the curve (AUC) and 95% confidence intervals (CI) for each biomarker were as follows: Log2 NLR: AUC = 0.818 (95%CI: 0.765-0.872); Log2 MLR: AUC = 0.808 (95%CI: 0.753-0.863); Log2 PLR: AUC = 0.600 (95%CI: 0.529-0.672); Log2 SIRI: AUC = 0.868 (95%CI: 0.823-0.913); Log2 SII: AUC = 0.768 (95%CI: 0.708-0.828); Log2 AISI: AUC = 0.805 (95%CI: 0.750-0.860). Among all biomarkers, log2 SIRI exhibited the highest discriminative ability for predicting GU. According to pairwise Delong tests, the AUC of log2 SIRI was significantly higher than those of the other five biomarkers (P < 0.05 for all comparisons) (Figure 2).
Figure 2 Receiver operating characteristic curves for complete blood count-derived inflammatory marker as a predictor of gastric ulcer.
AUC: Area under curve; CI: Confidence interval; NLR: Neutrophil-to-lymphocyte ratio; MLR: Monocyte-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; SIRI: Systemic inflammatory response index; SII: Systemic immune-inflammation index; AISI: Aggregate index of systemic inflammation.
Stepwise logistic regression and LASSO regression
LASSO regression showed that SIRI among the CBC-derived inflammatory markers was the variable with a unique coefficient not penalized as 0 (Figure 3). Stepwise regression revealed that SIRI was the only CBC-derived inflammatory marker retained in the model (Figure 3).
Figure 3 Screening of variables based on least absolute shrinkage and selection operator and stepwise regression.
OR: Odds ratio; SCr: Serum creatinine; BUN: Blood urea nitrogen; NLR: Neutrophil-to-lymphocyte ratio; MLR: Monocyte-to-lymphocyte ratio; PLR: Platelet-to-lymphocyte ratio; SIRI: Systemic inflammatory response index; SII: Systemic immune-inflammation index; AISI: Aggregate index of systemic inflammation.
DISCUSSION
In this study, we comprehensively explored the relationships between six commonly used CBC-derived inflammatory biomarkers and the prevalence of GU. The results showed that NLR, MLR, PLR, SIRI, SII, and AISI were all significantly and positively correlated with GU prevalence. Among these, SIRI showed the strongest association. As novel indicators reflecting systemic inflammation and immune status, CBC-derived inflammatory biomarkers are inexpensive, readily available, and noninvasive. Therefore, they may serve as effective tools for the early screening and risk stratification of GU.
Numerous studies have demonstrated that elevated CBC-derived inflammatory markers are significantly associated with the diagnosis, progression, and prognosis of gastrointestinal malignancies such as gastric and colorectal cancers[26-32]. In this context, SIRI has recently gained prominence due to its ability to integrate multiple immune-inflammatory components and its superior predictive performance[33-37]. These biomarkers reflect the complex interplay between proinflammatory and immunosuppressive forces within the tumor microenvironment. For instance, SIRI is calculated based on neutrophil, monocyte, and lymphocyte counts, combining indicators of both innate immune activation and impaired adaptive immunity. Neutrophils contribute to cancer progression by promoting angiogenesis, inducing immunosuppression, and promoting metastasis[38]. By releasing cytokines and growth factors, neutrophils create an inflammatory environment that supports the proliferation and spread of cancer cells[39]. Peripheral monocyte levels are strongly associated with the density of tumor-associated macrophages, contributing to a microenvironment that favors cancer progression[40]. Reduced levels of lymphocytes may reflect immune evasion and impaired tumor surveillance, and tumor-infiltrating lymphocytes are known to play essential roles in shaping the tumor immune response[41].
Recent evidence further suggests that several CBC-derived inflammatory indices, such as NLR, PLR, SII, and especially SIRI, may serve as reliable predictors not only of disease presence, but also of clinical outcomes and progression in gastrointestinal conditions. For instance, in advanced gastric cancer treated with chemotherapy, pretreatment NLR and PLR levels, as well as their longitudinal changes, independently predicted progression-free and overall survival[42]. Similarly, among gastric cancer patients receiving curative surgery, higher preoperative NLR and PLR levels were significantly linked to greater postoperative morbidity and mortality[43]. Notably, a recent study using propensity score matching revealed a significant association between systemic inflammatory status and prognosis in patients with early gastric cancer and pyloric stenosis undergoing radical resection. In that study, NLR, SII, and SIRI were all predictive of patient outcomes, with SIRI showing the highest prognostic value among inflammatory indices[44]. These results highlight that SIRI, which combines neutrophil, monocyte, and lymphocyte counts, could serve as a more comprehensive and reliable marker of systemic inflammation and immune dysfunction, demonstrating strong potential as a prognostic biomarker.
In addition to SIRI, other CBC-derived biomarkers have also shown clinical relevance in gastrointestinal diseases. For example, NLR and PLR have been reported to aid in the diagnosis of peptic ulcers and may predict the risk of severe postoperative complications[13,14]. While the precise mechanisms were not explicitly addressed in some of these studies, the predictive value of these markers is likely attributed to their reflection of systemic inflammatory burden and immune homeostasis imbalance.
It is well recognized that inflammation and oxidative stress play central roles in the development of GU[45]. Activation of intracellular signaling pathways, including nuclear factor kappa-B and mitogen-activated protein kinase, in gastric epithelial cells triggers the release of pro-inflammatory cytokines such as interleukin (IL)-8. These cytokines promote neutrophil infiltration into the gastric mucosa[46-48]. In addition, both neutrophils and monocytes can generate a strong oxidative burst, releasing large amounts of reactive oxygen species (ROS), damaging epithelial cells, and weakening the gastric mucosal barrier function[8,49,50]. ROS also upregulate matrix metalloproteinase-9, facilitating extracellular matrix degradation an essential step in ulcer development[51]. Activated neutrophils and monocytes release proinflammatory mediators including tumor necrosis factor-α, IL-6, and monocyte chemoattractant protein-1 that enhance mucosal inflammation and promote leukocyte recruitment[52,53]. In contrast, the decrease in the number of lymphocytes in the peripheral blood may reflect suppression of the adaptive immune function, including decreased ability to regulate inflammation and delayed mucosal repair. The above features, elevated neutrophils and monocytes accompanied by decreased lymphocytes, together create a highly proinflammatory, tissue-destructive microenvironment, which in turn drives the onset of gastric mucosal damage and the formation and progression of GUs. It is worth noting that SIRI is constructed based on the ratio of neutrophils, monocytes, and lymphocytes, and therefore, an elevated SIRI not only reflects a continuous inflammatory activation but also may play a proinflammatory and injurious role in GU occurrence and development. This finding suggests that SIRI has the potential to be used as an indicator of ulcer risk or severity and may be involved in its pathophysiological mechanism, which is worthy of further study.
This study had several strengths. First, NLR, MLR, PLR, SIRI, SII, and AISI are emerging inflammatory biomarkers that reflect systemic inflammation and immune status, and have demonstrated promising clinical utility. To our knowledge, this is the first population-based study to comprehensively assess the relationships between all six CBC-derived inflammatory markers and GU, offering important epidemiological evidence in this area. Second, we analyzed and directly compared these six biomarkers within the same population, which facilitates a more practical and precise reference for future clinical applications. This approach also has the potential to reduce the minimum required sample size in similar modeling studies. Third, GU diagnosis was based on gastroscopic and histopathological confirmation rather than self-reported symptoms, minimizing the risk of diagnostic bias. Finally, employing multiple models and statistical approaches to analyze the relationships between CBC-derived inflammatory biomarkers and GU strengthens the robustness and reliability of our results.
Despite these strengths, several limitations warrant consideration. Firstly, the sample size was limited, and participants were drawn from a single geographic area, which may restrict the generalizability of our findings. Secondly, given the cross-sectional design of the study, causal relationships between CBC-derived inflammatory biomarkers and GU cannot be determined. Furthermore, due to the limited duration of the study, we could not evaluate the prognostic significance of CBC-derived inflammatory biomarkers in patients with GU. Additional research is needed to investigate their potential in predicting disease progression and clinical outcomes within this population. Finally, we verified the close association between SIRI and GU by LASSO regression and stepwise regression; however, there are some limitations in these methods, and we may be able to make new discoveries through neural network modeling or artificial intelligence techniques[54].
CONCLUSION
Our study revealed a significant positive correlation between the NLR, MLR, PLR, SIRI, SII, and AISI and the prevalence of GU. Among them, SIRI is the most closely associated with GU prevalence.
Footnotes
Provenance and peer review: Unsolicited article; Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Gastroenterology and hepatology
Country of origin: China
Peer-review report’s classification
Scientific Quality: Grade A, Grade A, Grade B
Novelty: Grade A, Grade B, Grade B
Creativity or Innovation: Grade B, Grade B, Grade B
Scientific Significance: Grade A, Grade B, Grade B
P-Reviewer: Hou WM, MD, China; Li LB, MD, Professor, China S-Editor: Fan M L-Editor: A P-Editor: Wang WB
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