Upregulation of B7-H4 Is Involved in and Related to the Severity of Acute Pancreatitis.

The expression and clinical significance of co-stimulator B7-H4 in acute pancreatitis (AP) is still unclear. In vitro study showed that the expression of soluble B7-H4 (sB7-H4) and proportions of membrane B7-H4-positive CD14+ cells in the peripheral blood mononuclear cells were upregulated in response to stimulation with plasma from AP patients, lipopolysaccharides, or tumor necrosis factor α (TNF-α). sB7-H4 in the plasma of AP patients were positively correlated with interleukin (IL)-6, IL-10, IL-17A, TNF-α, and interferon-γ The areas under the curves (AUCs) of receiver operating characteristic (ROC) curves of plasma sB7-H4 to distinguish the AP patients from healthy donors, the mild AP (MAP) from the moderately severe acute pancreatitis (MSAP)+severe acute pancreatitis (SAP) or the SAP from the MAP+MSAP were 0.78 (P < 0.001) or 0.773 (P < 0.001) or 0.764 (P < 0.001). sB7-H4 in the plasma of patients were positively correlated with the RANSON scores, Bedside Index of Severity of Acute Pancreatitis scores, Marshall scores, and Acute Physiology And Chronic Health Evaluation II scores; and the AUCs of ROC curves of plasma sB7-H4 in the prediction of local complications was 0.726 (P = 0.001). In conclusion, the co-stimulator B7-H4 is involved in the immune response in AP.

Clinical significance of changes in AFP, HTATIP2/TIP30, B7-H4 and inflammatory cytokines after transcatheter arterial chemoembolization.

PURPOSE: To explore the clinical significance of changes in alpha-fetoprotein (AFP), HIV-1 TAT interactive protein 2/TAT interactive protein 30 (HTATIP2/TIP30), B7-H4 and inflammatory cytokines after transcatheter arterial chemoembolization (TACE). METHODS: A total of 84 hepatocellular carcinoma (HCC) patients admitted to the Department of Hepatobiliary Surgery and the Department of Interventional Radiology of our hospital from January 1, 2017 to December 31, 2018 were randomly enrolled and divided into an experimental group and a control group according to treatment methods. The expression levels of AFP mRNA, HTATIP2/TIP30, B7-H4 and inflammatory cytokines were detected before and after treatment, the short-term efficacy was followed up and analyzed, and the correlation between the two was statistically analyzed. RESULTS: The AFP expression level in the two groups of patients was lower after treatment than before treatment, this reduction being more obvious in the experimental group (receiving TACE) than in the control group. Although the levels of serum HTATIP2/TIP30 and B7-H4 were decreased after treatment in both groups, and they were lower after treatment than those before treatment in the control group, lower levels were registered in the control group. Both groups of patients had lower expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) after treatment compared with those before treatment, this decrease being more significant in the experimental group than in the control group. Moreover, the total short-term efficacy rate and the improvement rate of the quality of life were higher in the experimental group than in the control group, although no statistical difference in the survival rate was found between the two groups after 1-year follow-up. The serum level of B7-H4 in the group with good efficacy was lower than in the group with poor efficacy before treatment, and it declined in both groups after treatment, with a lower level in the former than in the latter. Furthermore, the group with good efficacy had a lower level of serum HTATIP2/TIP30 than the group with poor efficacy, while both groups had a decreased level after treatment, with a lower level in the former than in the latter. CONCLUSION: Interventional therapy for primary HCC has good short-term efficacy. It can reduce the levels of serum HTATIP2/TIP30, B7-H4, AFP and inflammation-related indexes, improve the liver function and the patients' quality of life.

Combined detection of CA19-9 and B7-H4 in the diagnosis and prognosis of pancreatic cancer.

BACKGROUND: There were no specific indicators for the early detection of pancreatic cancer. OBJECTIVE: To analyze the diagnostic and prognostic value of CA19-9 plus B7-H4 detection in preoperative serum or surgical tissues of patients with pancreatic cancer. METHODS: One hundred and eighty-eight patients with pancreatic cancer and 25 controls were recruited. Their preoperative serum CA19-9 level was detected chemiluminescently, and B7-H4 expression in pancreatic cancer tissues was assessed immunohistochemically. The diagnostic and prognostic utility of detecting CA19-9, B7-H4 and their combination was evaluated. RESULTS: CA19-9 and B7-H4 levels were significantly upregulated in patients with pancreatic cancer compared with those in controls. The diagnostic value of combined CA19-9 plus B7-H4 detection was markedly better than that achieved from their separate detection analyzed with receiver operating characteristic curve. Sensitivity and specificity of the combined detection in the pancreatic cancer group was significantly increased compared with single detection. B7-H4 detection showed better prognostic value than detection of CA19-9. However, CA19-9 had high sensitivity and low specificity, while B7-H4 showed the opposite. The sensitivity of the combined prognosis was not significantly different to B7-H4 alone. CONCLUSION: The combined detection of CA19-9 and B7-H4 could become a new method for the clinical diagnosis and prognosis of pancreatic cancer.

The effects of interventional therapy on serum HTATIP2/TIP30, B7-H4 and short-term curative effect in primary hepatocellular carcinoma.

OBJECTIVE: To explore the effects of interventional therapy on human immunodeficiency virus (HIV)-1 Tat interactive protein 2/Tat interactive protein 30 (HTATIP2/TIP30), B7-H4 and short-term curative effect in primary hepatocellular carcinoma. PATIENTS AND METHODS: 62 patients with primary hepatocellular carcinoma admitted in our hospital from June 2015 to June 2016 were enrolled in this study and divided into observation group (n = 31) and control group (n = 31) according to the random number table. The patients in the control group were treated with radiofrequency ablation, and the patients in the observation group were treated with transcatheter arterial chemoembolization (TACE). The patients in both groups received liver protection therapy, hydration, antiemetic and stomach protection. The curative effects, the serum HTATIP2/TIP30, B7-H4, alanine aminotransferase (ALT) and total bilirubin in serum (TBIL), life quality before and after treatment, and survival during the 1-year follow-up, were compared. RESULTS: The total short-term effective rate (70.97%) was higher than the control group (38.71%) (p < 0.05). The serum levels of HTATIP2/TIP30 and B7-H4 were decreased after treatment in both groups (observation group: t = 17.1838, 18.9795, control group: t = 8.3787, 10.6393, p < 0.05). The serum levels of HTATIP2/TIP30 and B7-H4 after treatment in the observation group were lower than the control group (t = 12.2975, 10.5361, p < 0.05). The levels of ALT and TBIL were decreased after treatment (observation group: t = 15.1716, 34.5771, control group: t = 8.3374, 17.3015, p < 0.05). The levels of ALT and TBIL were lower in the observation groups than the control group (t = 15.2697, 16.8592, p < 0.05). The improvement rate of life quality in the observation group (80.65%) was higher than the control group (54.84%) (p < 0.05). The survival rates of the two groups after 1-year follow-up were not statistically different (p > 0.05). CONCLUSIONS: The short-term curative effect of interventional therapy of primary hepatocellular carcinoma is good. It can decrease serum HTATIP2/TIP30 and B7-H4, improves the liver function and the life quality of patients, prolonging the survival time. It has a high research value and it is worthy of further application.

Clinical Value of Combined Determination of Serum B7-H4 with Carcinoembryonic Antigen, Osteopontin, or Tissue Polypeptide-Specific Antigen for the Diagnosis of Colorectal Cancer.

AIM: B7-H4 is member of the B7 family that negatively regulates the immune response, which are associated with tumor development and prognosis. The present study is aimed at examining serum B7-H4 expression and exploring its contribution to diagnosis in patients with colorectal cancer. METHODS: We determined serum expressions of B7-H4, carcinoembryonic antigen (CEA), osteopontin (OPN), and tissue polypeptide-specific antigen (TPS) in 59 patients with colorectal cancer and 29 healthy volunteers and analyzed the diagnostic value of B7-H4 combined with CEA, OPN, or TPS detection for colorectal cancer. B7-H4, OPN, and TPS serum expressions were measured by enzyme-linked immunosorbent assay, and CEA was measured by electrochemical luminescence detection. RESULTS: Serum B7-H4 levels were significantly higher in colorectal cancer patients compared with paired normal controls (P = 0.001). B7-H4 serum level was positively correlated with infiltration depth, tumor masses, and lymph node metastasis (P = 0.004, P = 0.016, and P = 0.0052, respectively). We also detected serum expression of B7-H4 before and after radical resection and showed that B7-H4 levels decreased significantly during the first week postoperation (P = 0.0064). We used receiver operating characteristic (ROC) curve analysis to indicate the potential diagnostic values of these markers. The areas under the ROC curves (AUC) for B7-H4, OPN, TPS, and CEA were 0.867, 0.805, 0.812, and 0.833, respectively. The optimal sensitivity and specificity of B7-H4 for discriminating between colon cancer patients and healthy controls were 88.2% and 86.7%, respectively, using a cut-off of value of 78.89 ng/mL. However, combined ROC analysis using B7-H4 and CEA revealed an AUC of 0.929, with a sensitivity of 98.9% and a specificity of 80.4% for discriminating colon cancer patients from healthy controls. CONCLUSIONS: B7-H4 was highly expressed in the serum in colorectal cancer patients. Detection of B7-H4 plus CEA showed significantly increased sensitivity and specificity for discriminating between colorectal cancer patients and healthy controls compared to individual detection of these markers. Combined detection of serum B7-H4 and CEA may thus have the potential to become a new laboratory method for the early clinical diagnosis and prognostic evaluation of colorectal cancer.

Serum B7 homologous body 4 for the diagnosis of ovarian cancer in Chinese Han women: A meta-analysis.

OBJECTIVE: The aim of this study is to investigate the clinical value of serum B7 homologous body 4 (B7-H4) protein detection for the diagnosis of ovarian cancer (OC) in Chinese Han women by pooling published data. METHODS: A systematic literature search was conducted in Cochrane Library, PubMed, EMBASE, Wanfang, and China National Knowledge Infrastructure databases. The bivariate model was utilized to calculate the pooled estimates. Publication bias was assessed by using funnel plots and Deek's test. RESULTS: After the review, ten publications were found to meet our inclusion criteria. The overall diagnostic sensitivity and specificity of B7-H4 in OC were 0.782 (95% confidence interval [CI]: 0.732-0.825) and 0.870 (95% CI: 0.804-0.916), respectively. The area under summary receiver operating characteristic curves was 0.86 (95% CI: 0.83-0.89). No significant publication bias was observed in the included studies. CONCLUSION: Serum B7-H4 detection, either alone or in combination with carbohydrate antigen 125, has an acceptable value in the diagnosis of OC.

Serum soluble B7-H4 is a prognostic marker for patients with non-metastatic clear cell renal cell carcinoma.

BACKGROUND: B7-H4 is a member of the B7 family of immune-regulatory ligands and is considered to be a negative regulator of the immune response. We investigated the clinical significance of serum soluble B7-H4 in patients with non-metastatic clear cell renal cell carcinoma. METHODS: We analyzed 108 patients in whom non-metastatic clear cell renal cancer was diagnosed at Tokyo Metropolitan Tama Medical Center between 2008 and 2013. We measured the serum soluble B7-H4 level using the Enzyme-Linked ImmunoSorbent Assay (ELISA) and evaluated the association between the peripheral blood neutrophil count and sB7-H4 as well as the utility of soluble B7-H4 as a prognostic biomarker for clear cell renal cancer. The Cox proportional hazards regression model was used to assess the PFS and OS with the soluble B7-H4 level. RESULTS: We detected high levels of soluble B7-H4 in the sera of 56% of patients with non-metastatic clear cell renal cell carcinoma versus only 10% of healthy donors. Elevated soluble B7-H4 levels were associated with changes in an elevated peripheral blood neutrophil count. The increase of soluble B7-H4 also was significantly associated with poor PFS and OS. Multivariate analysis showed that the elevation of the soluble B7-H4 level was an independent prognostic factor for PFS and OS. CONCLUSIONS: Our data suggest that the association between serum soluble B7-H4 and peripheral blood neutrophil count, as well as the evaluation of serum soluble B7-H4 expression is a useful tool for predicting the prognosis of patients with non-metastatic clear cell renal cell carcinoma.

Diagnosis value of serum soluble B7-H4 expression in non-small cell lung cancer.

INTRODUCTION: B7-H4, a member of the inhibitory B7 family, can restrain T cell proliferation, activation, cytokine secretion, and may be involved in immune evasion in cancer patients. OBJECTIVES: This aim of the study was to determine the expression level of soluble B7-H4 (sB7-H4) in circulation and to subsequently evaluate the clinical significance of circulating sB7-H4 in patients with non-small cell lung cancer (NSCLC). METHODS: Serum specimens from 128 patients with NSCLC, 100 healthy volunteers (HV), and 80 patients with benign lung diseases (BLD) were collected. The concentrations of sB7-H4 were measured by sandwich enzyme-linked immunosorbent assay. RESULTS: Serum sB7-H4 levels in patients with NSCLC were significantly higher than those in patients with BLD (P < 0.05), or those in HV (P < 0.05). Using a cutoff of 27.8 ng/mL, the sensitivity and specificity of sB7-H4 in differentiating between patients with NSCLC and patients with BLD, and between patients with NSCLC and HV was, 46.9% and 92.5%, and 54.7% and 95.0%, respectively. An area under the curve (AUC) for NSCLC resulting from sB7-H4 (0.863), which was significantly better than any other tumour markers tested including CA125 (0.763), and CEA (0.775). CONCLUSION: In conclusion, assessment of serum sB7-H4 levels could be considered as a diagnostic biomarker for NSCLC.

B7-H4 is Predictive of Poor Prognosis in Patients with Gastric Cancer.

BACKGROUND Recently, some studies were performed to evaluate the relevance of B7-H4 and gastric cancer (GC) prognosis. However, the results remained controversial. Therefore, we performed the present meta-analysis. MATERIAL AND METHODS We performed a systematic search in PubMed and Web of Science databases. All data were extracted and reviewed from each eligible study independently by 2 investigators. The strength of association between B7-H4 and GC prognosis was assessed by computing odds ratio (OR) with its corresponding 95% confidence interval (CI). RESULTS Six studies that evaluated the association between B7-H4 and GC prognosis were included. The results showed a statistically significant association of B7-H4 and GC prognosis (OR=1.63, 95%CI=1.30-2.03). Furthermore, we conducted subgroup analysis based on source of B7-H4; the results from blood (OR=1.71; 95%CI, 1.09-2.68) and tissue (OR=1.60; 95%CI, 1.03-2.07) indicated B7-H4 was significantly associated with poor prognosis. CONCLUSIONS This meta-analysis suggests that GC patients with high B7-H4 have poor prognosis.

Higher preoperative serum levels of PD-L1 and B7-H4 are associated with invasive and metastatic potential and predictable for poor response to VEGF-targeted therapy and unfavorable prognosis of renal cell carcinoma.

Renal cell carcinoma (RCC) is an immunogenic and proangiogenic cancer. Although antivascular endothelial growth factor (VEGF) therapies achieve impressive responses in some patients, many tumors eventually develop resistance to such therapy. The B7 family molecules such as CTLA-4, PD-1, and PD-L1 are pivotal players in immune checkpoints that positively or negatively regulate various immune responses. Recently, immunotherapy based on blocking immune checkpoints with anti-CTLA4, anti-PD-1, or anti-PD-L1 antibodies has been proposed as a potential new approach to the treatment of metastatic RCC. Higher expression of PD-L1 and B7-H4 in the tumors is associated with a poor prognosis in RCCs, however, the clinical impact of serum levels of B7 family molecules has not been elucidated in patients with metastatic RCCs receiving VEGF-targeted agents. We assessed the preoperative serum levels of B7 family molecules, including CD80, CD86, PD-1, PD-L1, B7-H3, B7-H4, and CTLA-4, and CD28 in RCC patients, and determined their relations with various clinicopathological characteristics. Elevated preoperative serum levels of PD-L1 and B7-H4 were correlated with less differentiated tumors, higher invasive and metastatic potential, a worse response to anti-VEGF therapy, and shorter overall survival. These findings suggested that investigating preoperative serum levels of PD-L1 and B7-H4 might not only be useful to assess the biological aggressiveness of RCCs, but also to predict the efficacy of anti-VEGF therapy and the eventual prognosis, indicating the future design of clinical trials of therapies targeting immune checkpoint in advanced RCCs.

A Biomarker Panel Increases the Diagnostic Performance for Epithelial Ovarian Cancer Type I and II in Young Women.

BACKGROUND/AIM: To assess preoperative blood levels of a biomarker panel in relation to the new classification system of epithelial ovarian cancer (EOC) type I and II. PATIENTS AND METHODS: Preoperative plasma levels of B7-family protein homolog 4 (B7-H4), intact and cleaved soluble urokinase plasminogen activator receptor (suPAR), human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) were analyzed in 350 patients with adnexal lesions. RESULTS: The levels of suPAR(II-III), HE4, CA125 were all higher in EOC II than in EOC I, borderline and benign ovarian tumors. B7-H4 was increased in EOC II compared with benign ovarian tumors. The combination of suPAR(II-III), HE4, CA125 and age in premenopausal women discriminates EOC and borderline tumors from benign tumors to higher accuracy compared to the Risk of Ovarian Malignancy Algorithm (p=0.007). CONCLUSION: The biomarker panel suPAR(II-III), HE4, CA125 and age in premenopausal women improved discrimination of malignant and benign ovarian tumors. The plasma levels of B7-H4 were increased in patients with EOC II compared to those with benign ovarian tumors.

Circulating B7-H4 in serum predicts prognosis in patients with hepatocellular carcinoma.

B7-H4 is member of the B7 family that negatively regulates the immune response, which are important for fine-tuning of the tumor microenvironment. Dysregulation of B7-H4 expression has been associated with tumor progression. However, expression level of B7-H4 in hepatocellular carcinoma (HCC) tissues is still a controversial topic. In addition, whether serum B7-H4 expression of HCC patients has any clinical value is unknown. We compared serum levels of B7-H4 in patients with HCC and healthy controls by using the ELISA method. Association between serum B7-H4 expression level and clinical parameters of HCC was further investigated. Log-rank test and Kaplan-Meier method were employed to evaluate the overall survival rate of HCC patients. Univariate and multivariate analysis of prognostic factors were performed with the Cox regression model. Our results showed that HCC patients had significantly higher serum B7-H4 level as compared with healthy controls (P < 0.001). In addition, serum B7-H4 expression was correlated with HCC clinical parameters including serum AFP expression and TNM stage. HCC patients in the higher serum B7-H4 expression group had a poorer 5-year overall survival rate (P = 0.028). Moreover, serum B7-H4 expression was shown to be an independent prognostic factor for HCC (P = 0.034). The findings from this study suggest that serum B7-H4 is an independent prognostic indicator for HCC and may be a promising biomarker for early diagnosis as well as disease prognosis of HCC.

Evaluation of serum and pleural levels of soluble B7-H4 in lung cancer patients with pleural effusion.

OBJECTIVE: To evaluate the diagnostic value of sB7-H4 and CEA in both serum and pleural effusion of lung cancer patients. METHODS: Levels of sB7-H4 and CEA in 90 patients with malignant pleural effusion due to lung cancer and 58 patients with benign pleural effusion were measured by ELISA. RESULTS: The sB7-H4 and CEA levels in pleural effusion, serum and their ratio (F/S) were higher in lung cancer group than that in benign group (p < 0.01). The diagnostic efficiency of sB7-H4 combined CEA was superior to either sB7-H4 or CEA. CONCLUSIONS: Measurement of sB7-H4 and CEA might be useful diagnostic value for malignant effusion.

B7-H4 expression is associated with tumor progression and prognosis in patients with osteosarcoma.

Increasing evidences have demonstrated that B7-H4 is associated with tumor development and prognosis. However, the clinical significance of B7-H4 expression in human osteosarcoma (OS) remains unclear. The aim of present study was to examine the B7-H4 expression and to explore its contribution in OS. B7-H4 expression in OS tissues was examined by immunohistochemistry. Soluble B7-H4 (sB7-H4) levels in blood were examined by ELISA. The association of B7-H4 expression with clinicopathological factors or prognosis was statistically analyzed. Our findings demonstrated that B7-H4 expression in OS tissues was significantly higher than those in paired normal bone tissues (P < 0.001). sB7-H4 level in OS serum samples was significantly higher than that in healthy controls (P = 0.005). High B7-H4 expression in tissues and sB7-H4 level were both correlated with advanced tumor stage (P < 0.001, P = 0.017, resp.) and distant metastasis (P = 0.034, P = 0.021, resp.). Additionally, high B7-H4 expression or serum sB7-H4 levels were significantly related to poor overall survival (P = 0.028, P = 0.005, resp.). B7-H4 in tissues and serum samples were an independent factor for affecting the survival time of OS patients (P = 0.004, P = 0.041, resp.). Collectively, our data suggest that the evaluation of B7-H4 expression in tissues and blood is a useful tool for predicting the progression of osteosarcoma and prognosis.

Diagnostic value of serum B7-H4 for hepatocellular carcinoma.

BACKGROUND: Previous studies have suggested the abnormal expression of soluble B7-H4 (sB7-H4) in circulation in cancer patients. The aim of present study was to examine the sB7-H4 expression in serum and to investigate the correlations between sB7-H4 levels and clinicopathologic parameters as well as the survival rate of patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Circulating sB7-H4 levels in blood specimens from 93 patients with HCC and 55 healthy volunteers were examined by enzyme-linked immunosorbent assay. The association of sB7-H4 levels with clinicopathologic factors, overall survival (OS), and time to recurrence were statistically analyzed. RESULTS: sB7-H4 levels in HCC patients were significantly higher than that in healthy controls (49.12 ± 3.10 versus 31.66 ± 2.59 ng/mL, P < 0.001). High sB7-H4 levels were correlated with tumor size (P = 0.007), tumor invasion (P = 0.037), tumor differentiation (P = 0.044) and tumor-node metastasis stage (P < 0.001). In addition, high sB7-H4 levels were significantly related to poor OS and higher recurrence probability (P = 0.002, P = 0.014, respectively). High sB7-H4 levels were independent prognostic factors for both OS (hazard ratio = 2.497; 95% confidence interval, 1.133-3.789; P = 0.009) and time to recurrence (hazard ratio = 2.33; 95% confidence interval, 1.247-4.179; P = 0.008). CONCLUSIONS: Detection of sB7-H4 in serum might serve as a clinical predictor in the diagnosis or prediction of clinical outcomes for the patients with HCC.

Ovarian cancer biomarkers: current state and future implications from high-throughput technologies.

Ovarian cancer remains the most lethal gynecological malignancy worldwide and survival rates have remained unchanged in spite of medical advancements. Much research has been dedicated to the identification of novel biomarkers for this deadly disease, yet it has not been until recently that a few serum-based tests have been added to carbohydrate antigen 125 as Food and Drug Administration-approved tests for ovarian cancer. This lack of success in identifying clinically relevant biomarkers has been largely attributed to poor study design and bias leading to false discoveries or identification of second-tier biomarkers. Fortunately, a better understanding of the guidelines used to assess the clinical utility of a biomarker and the various phases of biomarker development will aid in avoiding such biases. As well, advances in high-throughput technologies have caused a renewed interest in biomarker discovery for ovarian cancer using alternative strategies such as targeted sequencing and proteomics. In this chapter, we will review the current state of ovarian cancer biomarker research with a focus on diagnostic serum markers. Furthermore, we will examine the standard practice guidelines' criteria for acceptance of a biomarker into the clinic as well as emerging high-throughput approaches to the discovery of novel ovarian cancer biomarkers.

Serum B7-H4 expression is a significant prognostic indicator for patients with gastric cancer.

BACKGROUND: B7-H4 is a novel B7 ligand that plays an important role in the T cell-mediated immune response as a negative regulator. Previous studies have suggested the aberrant expression of membrane B7-H4 in tumor cells. The aim of this study is to determine the expression levels of preoperative soluble B7-H4 (sB7-H4) in circulation and to investigate the correlations between sB7-H4 levels and clinicopathological parameters as well as the survival rate of patients with gastric cancer. METHODS: Blood specimens from 132 patients with gastric cancer and 63 healthy volunteers were analyzed by sandwich enzyme-linked immunosorbent assay. RESULTS: Median concentrations of sB7-H4 in patients with gastric cancer were significantly higher than those in healthy volunteers (16.85 versus 10.46 ng/mL; P = 0.008). Median levels of sB7-H4 were significantly correlated with tumor size, lymph node metastasis, the depth of tumor invasion and tumor-node-metastasis classification (P = 0.002, P = 0.001, P = 0.041 and P <0.001, respectively), but not with sex, age, tumor location or histological subtype (all P >0.05). Additionally, the overall survival rate was significantly lower in patients with high sB7-H4 levels when compared with low sB7-H4 levels (50.0% versus 77.3%, χ2 = 10.78, P = 0.001). Moreover, multivariate analysis demonstrated that the risk of death was significantly higher in patients with high sB7-H4 levels than in those with low sB7-H4 levels (P = 0.039). CONCLUSIONS: sB7-H4 is a valuable blood marker for predicting the progression and prognosis of patients with gastric cancer.