Du YL, Shi CJ, Gao FY, Xie SJ, Zhang MN, Zhang ZQ, Qiu W, Ming Y. Prognostic value of serum aldo-keto reductase family 1 member B10 in hepatocellular carcinoma. World J Gastrointest Surg 2026; 18(5): 116672 [DOI: 10.4240/wjgs.v18.i5.116672]
Corresponding Author of This Article
Ying Ming, MM, Department of Laboratory Medicine, The Affiliated Hospital of Chengde Medical University, No. 36 Nanyingzi Street, Shuangqiao District, Chengde 067000, Hebei Province, China. 18503145756@163.com
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Du YL, Shi CJ, Gao FY, Xie SJ, Zhang MN, Zhang ZQ, Qiu W, Ming Y. Prognostic value of serum aldo-keto reductase family 1 member B10 in hepatocellular carcinoma. World J Gastrointest Surg 2026; 18(5): 116672 [DOI: 10.4240/wjgs.v18.i5.116672]
Yun-Ling Du, Shou-Jun Xie, Meng-Na Zhang, Zhu-Qing Zhang, Wei Qiu, Ying Ming, Department of Laboratory Medicine, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
Chang-Jiang Shi, Department of Joint Surgery, The Affiliated Hospital of Chengde Medical University, Chengde 067000, Hebei Province, China
Fang-Yuan Gao, Department of Integrated Traditional Chinese and Western Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing 100000, China
Author contributions: Du YL designed the research and wrote the first manuscript; Du YL, Shi CJ, Gao FY, Xie SJ, Zhang MN, Zhang ZQ and Qiu W contributed to conceiving the research and analyzing data; Du YL and Ming Y conducted the analysis and provided guidance for the research. All authors reviewed and approved the final manuscript.
Supported by the Science and Technology Program of Chengde, No. 202109A064.
Institutional review board statement: The study was approved by the Institutional Review Board of the Affiliated Hospital of Chengde Medical University (Approval No. CYFYLL2021104).
Informed consent statement: Because this study used anonymized data, informed consent was not required.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Corresponding author: Ying Ming, MM, Department of Laboratory Medicine, The Affiliated Hospital of Chengde Medical University, No. 36 Nanyingzi Street, Shuangqiao District, Chengde 067000, Hebei Province, China. 18503145756@163.com
Received: January 13, 2026 Revised: February 4, 2026 Accepted: March 10, 2026 Published online: May 27, 2026 Processing time: 134 Days and 4.1 Hours
Abstract
BACKGROUND
Hepatocellular carcinoma (HCC) incidence continues to rise, yet treatment options remain limited. Despite recent advances in early screening methods, most patients are still diagnosed at an advanced stage with poor prognosis. Therefore, accurate assessment of prognostic risk using molecular biomarkers is essential for the development of personalized treatment strategies.
AIM
To investigate the correlation between serum aldo-keto reductase family 1 member B10 (AKR1B10) levels and clinicopathological characteristics and prognosis in patients with HCC, and to evaluate the potential clinical value of AKR1B10 as a prognostic biomarker.
METHODS
A total of 102 patients with HCC admitted to the Affiliated Hospital of Chengde Medical University between May 2020 and May 2024 were enrolled as study subjects. Complete clinical data and survival follow-up information were collected. Based on the optimal cutoff value for serum AKR1B10 levels in diagnosing HCC (1584.97 pg/mL), determined using receiver operating characteristic curve analysis, patients were divided into a high-level group (≥ 1584.97 pg/mL, n = 75) and a low-level group (< 1584.97 pg/mL, n = 27). AKR1B10 levels were measured using enzyme-linked immunosorbent assay. In 41 patients who underwent surgical resection, serum AKR1B10 levels were measured preoperatively and at 1-2 days and 3-4 days postoperatively. The χ2 test or Fisher’s exact test was used to compare categorical data between the two groups. Survival analysis was performed using the Kaplan-Meier method, with intergroup comparisons performed using the log-rank test. Cox univariate and multivariate regression analyses were used to identify independent prognostic factors, and the Friedman test was used to compare serum AKR1B10 levels at different postoperative time points.
RESULTS
Significant differences were observed between the AKR1B10 high-level and low-level groups in tumor size (χ2 = 3.999, P < 0.05), ascites (χ2 = 3.902, P < 0.05), and Barcelona Clinic Liver Cancer stage (χ2 = 3.987, P < 0.05). The median survival was 17.0 months in the high-level group, significantly shorter than that in the low-level group (32.0 months; χ2 = 6.172, P < 0.05). Multivariate Cox regression analysis indicated that serum AKR1B10 level (hazard ratio = 1.819, 95% confidence interval: 1.009-3.280, P < 0.05) and ascites (hazard ratio =1.810, 95% confidence interval: 1.017-3.223, P < 0.05) were independent factors influencing survival in patients with HCC. Additionally, serum AKR1B10 levels were significantly decreased at 1-2 days postoperatively in the 41 patients who underwent surgery, with a continued downward trend at 3-4 days postoperatively (χ2 = 82.000, P < 0.01).
CONCLUSION
Serum AKR1B10 is an independent risk factor for prognosis in HCC, and high AKR1B10 levels are associated with unfavorable survival outcomes, indicating its potential value as a biomarker for prognostic risk assessment in patients with HCC.
Core Tip: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Despite recent improvements in diagnostic approaches and surgical techniques, the five-year survival rate for patients with advanced HCC remains low, largely due to the absence of early clinical symptoms and the lack of reliable diagnostic and prognostic biomarkers. Over the past decade, aldo-keto reductase family 1 member 10 has emerged as a potential biomarker for both the diagnosis and prognosis of HCC. This study aimed to investigate the correlation between serum aldo-keto reductase family 1 member 10 levels and prognosis in patients with HCC, evaluate its clinical value as a prognostic indicator, and provide a theoretical basis and research direction for individualized treatment strategies.
Citation: Du YL, Shi CJ, Gao FY, Xie SJ, Zhang MN, Zhang ZQ, Qiu W, Ming Y. Prognostic value of serum aldo-keto reductase family 1 member B10 in hepatocellular carcinoma. World J Gastrointest Surg 2026; 18(5): 116672
Hepatocellular carcinoma (HCC) ranks as the sixth most common malignancy worldwide and the third leading cause of cancer-related mortality, with an increasing incidence and limited treatment options[1,2]. The development of HCC is closely associated with multiple factors, primarily viral hepatitis, cirrhosis, alcoholic liver disease, and non-alcoholic fatty liver disease[3,4]. Despite recent advances in research and improvements in early screening methods, most patients are still diagnosed at an advanced stage, resulting in poor prognosis[5,6]. In addition, it remains difficult to establish a staging system that accurately predicts survival in all patients with HCC. Among the available staging systems, the tumor-node-metastasis (TNM) system is one of the most widely used[7]. However, The TNM staging system is based on postoperative pathological findings, which limits its clinical applicability because most patients with HCC are diagnosed at an advanced stage and are therefore ineligible for surgical resection[8]. Chun et al[9] further reported that the prognostic performance of the TNM system was worse than that of the Barcelona Clinic Liver Cancer (BCLC) system. The BCLC system has demonstrated better survival stratification and prognostic prediction compared with other staging systems[10]. However, the etiology of liver cancer in Asia (e.g., hepatitis B virus infection) differs from that in western countries (e.g., hepatitis C virus infection), resulting in differences in tumor biology and prognosis. Consequently, the BCLC staging system may underestimate prognosis for some Asian patients[11]. Therefore, accurate evaluation of prognostic risk using molecular biomarkers is essential for the development of individualized treatment strategies.
The identification of novel biomarkers to improve early diagnosis and prognostic assessment of HCC remains a major research focus. Among various potential biomarkers, aldo-keto reductase family 1 member B10 (AKR1B10) has attracted increasing attention. Previous studies have demonstrated elevated AKR1B10 levels in HCC tissues, suggesting its potential as a tumor marker for HCC[12,13]. However, the prognostic value of AKR1B10 tissue expression and its impact on patient survival remain controversial. Some studies suggest that AKR1B10 exerts carcinogenic effects[14,15], whereas others have identified it as a protective prognostic factor[16]. A meta-analysis indicated that AKR1B10 has a high diagnostic value for HCC and may serve as a novel screening marker[17]. Notably, AKR1B10 demonstrates excellent diagnostic performance for early-stage HCC and shows improved diagnostic accuracy when combined with alpha-fetoprotein (AFP). Furthermore, AKR1B10 level has been reported to predict overall survival (OS) and recurrence-free survival in patients with HCC following liver resection.
However, the prognostic value of serum AKR1B10 as a non-invasive marker in HCC has rarely been reported. This study was conducted to investigate the correlation between serum AKR1B10 levels and prognosis in patients with HCC and to evaluate its clinical value as a prognostic marker, thereby providing theoretical evidence and research direction for individualized treatment of HCC.
MATERIALS AND METHODS
Study subjects
This follow-up study was conducted using 102 patients with HCC admitted to the Affiliated Hospital of Chengde Medical University between May 2020 and May 2024. The study cohort was derived from a previously established patient population by the research group. The inclusion criteria and methods for serum AKR1B10 measurement have been described in detail in a prior study[18]. Based on the optimal cutoff value of serum AKR1B10 (1584.97 pg/mL), determined using receiver operating characteristic curve analysis, patients were divided into a high-level group (AKR1B10 ≥ 1584.97 pg/mL, n = 75) and a low-level group (AKR1B10 < 1584.97 pg/mL, n = 27). Additionally, serum AKR1B10 levels were dynamically measured preoperatively and at 1-2 days and 3-4 days postoperatively in 41 patients who underwent surgical resection.
Study methods
Baseline clinical and follow-up data were collected for all patients. Baseline clinical data included demographic characteristics (sex, age, and body mass index), personal history (smoking history and alcohol consumption), past medical history (viral hepatitis, cirrhosis, or diabetes mellitus), tumor-related clinical characteristics (number of tumors, tumor size, portal vein tumor thrombus, vascular tumor thrombus, lymph node or distant metastasis, ascites, microvascular invasion, satellite lesions, and BCLC stage), and laboratory parameters [liver function indices: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and albumin; coagulation index: Prothrombin time; and tumor marker: AFP]. Patients were followed-up through outpatient visits or telephone interviews, with the final follow-up completed in May 2025.
Statistical analysis
Statistical analysis was performed using SPSS version 25.0. Non-normally distributed quantitative data were expressed as median (interquartile rage). The Kruskal-Wallis H test was used for multi-group comparisons, followed by pairwise comparisons where appropriate. The χ2 test or Fisher’s exact test was applied for comparisons of categorical data. Survival analysis was conducted using the Kaplan-Meier method, with intergroup comparisons performed using the two-sided log-rank test. Cox univariate and multivariable regression analysis were used to identify prognostic risk factors. The Friedman test was used to compare serum AKR1B10 levels at different preoperative and postoperative time points. A P-value < 0.05 was considered statistically significant.
RESULTS
Patient characteristics and serum AKR1B10 levels
A total of 102 newly diagnosed, treatment-naïve patients with HCC were enrolled, all of whom completed serum AKR1B10 level measurement and follow-up. The cohort included 82 males and 20 females, with a median age of 60 years (range: 55-66 years). Based on the diagnostic cutoff value of serum AKR1B10 (1584.97 pg/mL) determined using receiver operating characteristic curve analysis in a previous study[18], patients were divided into a high-level group (≥ 1584.97 pg/mL, n = 75) and a low-level group (< 1584.97 pg/mL, n = 27).
Correlation between serum AKR1B10 levels and clinicopathological characteristics
Correlation analysis revealed statistically significant differences in tumor size, ascites, and BCLC stage between the high- and low-level groups (P < 0.05). In contrast, no statistically significant differences were observed between both groups in sex, age, smoking history, alcohol consumption, viral hepatitis, cirrhosis, antiviral therapy, number of tumors, portal vein tumor thrombus, vascular tumor thrombus, lymph node or distant metastasis, concomitant type 2 diabetes mellitus, microvascular invasion, satellite lesions, body mass index, AFP, clusterin, prothrombin time, ALT, AST, total bilirubin, or albumin (P > 0.05; Table 1).
Table 1 The relationship between serum aldo-keto reductase family 1 member B10 levels and clinical pathological characteristics of hepatocellular carcinoma patients, n (%).
Relationship between serum AKR1B10 levels and patient survival
The overall follow-up period was 12-60 months. By the final follow-up, 70 patients (68.6%) had died, and 32 patients (31.4%) survived. The median OS for all patients was 22.0 months [95% confidence interval (CI): 16.2-27.8]. The median OS was 32.0 months (95%CI: 21.2-42.7) in the low-level group and 17.0 months (95%CI: 11.0-23.0) in the high-level group. The difference in survival rates between the two groups was statistically significant (χ2 = 6.172, P < 0.05; Figure 1).
Figure 1 The survival curves of the low-level group and high-level group of serum aldo-keto reductase family 1 member B10.
AKR1B10: Aldo-keto reductase family 1 member B10.
Univariate and multivariate analyses of factors influencing patient survival
Univariate Cox regression analysis identified tumor size (≥ 5 cm), ascites, microvascular invasion, serum AFP (≥ 400 ng/mL), and high serum AKR1B10 levels as risk factors influencing the survival of patients with HCC (all P < 0.05). Variables showing statistical significance in the univariate analysis were subsequently incorporated into a multivariate Cox regression model. Multivariate analysis indicated that high serum AKR1B10 levels [hazard ratio (HR) = 1.819, 95%CI: 1.009-3.280, P < 0.05] and the presence of ascites (HR = 1.810, 95%CI: 1.017-3.223, P < 0.05) were independent risk factors influencing the survival of patients with HCC (Table 2).
Table 2 Cox regression analysis of the influencing factors on the survival time of hepatocellular carcinoma patients.
Peripheral blood samples were collected from the 41 patients with HCC who underwent surgical resection to measure serum AKR1B10 levels preoperatively and at 1-2 days and 3-4 days postoperatively. The results showed that the serum AKR1B10 level was 3518.15 (1538.52-4775.76) pg/mL preoperatively, then decreased significantly to 1112.48 (849.37-1525.81) pg/mL at 1-2 days postoperatively, and further decreased to 696.33 (648.45-847.88) pg/mL at 3-4 days postoperatively. Differences across time points were statistically significant (χ2 = 82.00, P < 0.01; Figure 2).
Figure 2 Changes in serum aldo-keto reductase family 1 member B10 concentrations before and after surgical resection in patients with hepatocellular carcinoma.
AKR1B10: Aldo-keto reductase family 1 member B10.
DISCUSSION
HCC, a malignant tumor with high incidence and mortality worldwide, necessitates refined prognostic assessment to support individualized treatment strategies and improve patient survival outcomes. Although multiple prognostic prediction models and staging systems for HCC have been developed, no universally accepted standard has been established to date[19,20]. In clinical practice, serum biomarkers are widely used for prognostic assessment due to their accessibility, reproducibility, and minimal invasiveness. AFP remains the most commonly used serum marker, and elevated AFP levels, particularly ≥ 400 ng/mL, have been consistently associated with aggressive tumor behavior, increased vascular invasion risk, and poor prognosis[21,22]. Protein induced by vitamin K absence or antagonist II serves as a supplementary marker, with elevated levels closely related to adverse pathological features, including portal vein invasion, tumor growth, and microvascular invasion. Currently, protein induced by vitamin K absence or antagonist II has been recognized by several international guidelines (e.g., American Association for the Study of Liver Diseases and European Association for the Study of the Liver) and is recommended for HCC diagnosis and prognostic assessment[23-25]. However, available serum biomarkers remain limited in terms of sensitivity, specificity, and independent prognostic performance. Therefore, identification of novel serum biomarkers with improved prognostic value is essential for refining HCC risk stratification and optimizing treatment strategies clinically.
With advances in molecular biology, an increasing number of potential serum prognostic markers have been explored, including AKR1B10, a secretory protein. Previous studies conducted by our research group preliminarily confirmed that serum AKR1B10 exhibits high sensitivity and specificity for the diagnosis of early-stage to mid-stage HCC, including AFP-negative HCC, suggesting its potential as a novel serological biomarker[18]. On this basis, the clinical value of serum AKR1B10 was comprehensively evaluated as a prognostic biomarker for HCC.
Several studies indicated that AKR1B10, as a member of the aldo-keto reductase family, may be involved in HCC development and progression through the regulation of apoptosis, oxidative stress, cellular metabolism, and signaling pathways[26-28]. However, the correlation between serum AKR1B10 levels and clinicopathological characteristics remains controversial. Xie et al[29] reported correlations between AKR1B10 levels and tumor progression indicators as well as liver function parameters, including tumor size, tumor number, portal vein invasion, ascites, TNM stage, Child-Pugh classification, AST, and ALT[12], whereas Wang et al[30] found no significant associations with these variables. In the present study, serum AKR1B10 levels were significantly correlated with tumor size, ascites, and BCLC stage. These findings are phenotypically consistent with previous findings indicating that AKR1B10 promotes tumor proliferation and mediates the tumor-associated inflammatory microenvironment[28,29,31]. Different from the results reported by Xie et al[29], no significant associations were observed between AKR1B10 levels and portal vein invasion, Child-Pugh classification, or other liver function parameters in this study. Such differences may result from the heterogeneity in study populations (e.g., etiological composition and baseline liver function). Notably, the highly selective association pattern observed in this study suggests that serum AKR1B10 levels may more directly reflect tumor activity and progression status. Furthermore, levels independent of AFP suggest that AKR1B10 may be associated with tumor biological information different from AFP, providing a new insight into HCC prognosis assessment.
Importantly, a significant correlation was observed between serum AKR1B10 levels and survival in patients with HCC. The significantly shorter median survival in the high-level group compared with the low-level group (17.0 months vs 32.0 months, χ2 = 6.172, P < 0.05) indicates that elevated serum AKR1B10 level is associated with poor clinical outcomes. Multivariate Cox regression analysis further demonstrated that serum AKR1B10 level (HR = 1.819, 95%CI: 1.009-3.280, P < 0.05) and the presence of ascites (HR = 1.810, 95%CI: 1.017-3.223, P < 0.05) were independent prognostic factors influencing survival in patients with HCC. These results are consistent with previous reports identifying serum AKR1B10 as a prognostic risk factor for HCC[29]. Moreover, the prognostic value of serum AKR1B10 was shown to be independent of several conventional indicators (e.g., tumor size and AFP level). The HR = 1.819 for AKR1B10 was comparable to that of ascites and exceeded that of some conventional prognostic factors, underscoring its strong independent prognostic capability and its potential role as an effective supplement to the existing HCC prognostic assessment systems.
Additionally, serum AKR1B10 levels decreased significantly in patients with HCC who underwent surgical resection. This rapid and significant decrease indicates that serum AKR1B10 sensitively reflects dynamic changes in tumor burden. Accordingly, AKR1B10 is considered a promising dynamic biomarker for evaluating therapeutic response following radical surgery. Measurement of serum AKR1B10 levels during the early postoperative period (1-4 days) effectively reflected tumor burden reduction, providing a theoretical basis for further exploration of its clinical application in evaluating surgical radicality, predicting early recurrence, and monitoring minimal residual lesions.
Several limitations of this study should be acknowledged. First, as a single-center study with a relatively small sample size, the statistical power may be limited, potentially affecting the detection of subtle but clinically meaningful associations. Second, the median follow-up duration ranged was 12-60 months, and longer-term survival outcomes were not fully captured. Given the need for long-term monitoring in HCC, the lack of long-term follow-up data may limit the long-term prognostic value of the findings. Further multi-center studies with larger cohorts and prolonged follow-up periods are warranted to enhance the robustness and generalizability of these results and to further clarify the long-term prognostic value of serum AKR1B10 in HCC.
CONCLUSION
In summary, serum AKR1B10 is an independent prognostic risk factor for HCC and demonstrates significant clinical value in prognosis assessment. It may serve as a novel and complementary serological biomarker to existing prognostic indicators in patients with HCC.
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