Diagnostic value of serum B7-H4 for hepatocellular carcinoma

Zhang, Cheng; Li, Yiming; Wang, Yang

doi:10.1016/j.jss.2015.04.034

Cited by 28 publications

(23 citation statements)

References 25 publications

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“…Zhang et al. reported in 93 human hepatocellular carcinoma (HCC) patients that soluble B7‐H4 levels in patients were significantly higher than that in healthy controls; high sB7‐H4 levels were correlated with tumor differentiation, tumor invasion, tumor‐node metastasis stage, and poor overall survival; high sB7‐H4 levels were independent prognostic factors for overall survival 32. These findings are consistent with our observation in RCCs in this study.…”

Section: Discussionsupporting

confidence: 92%

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

et al. 2016

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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.

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Section: Discussionsupporting

confidence: 92%

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

et al. 2016

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“…Consequently, B7-H4 knockout mice had less lung metastases than wild-type B7-H4 mice [34]. High B7-H4 expression level was positively associated with local invasion, poorer differentiation, distant metastasis, and lymph node metastasis [35], and was independent prognostic factors of OS [36]. Our study discovered discordance in expression of B7-H4 between the liver metastases and the matched primary pancreatic cancer.…”

Section: Discussionmentioning

confidence: 88%

Prognostic significance of B7-H4 expression in matched primary pancreatic cancer and liver metastases

et al. 2016

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Liver metastasis development in pancreatic cancer patients is common and confers a poor prognosis. Clinical relevance of biomarker analysis in metastatic tissue is necessary. B7-H4 has an inhibitory effect on T cell mediated response and may be involved in tumor development. Although B7-H4 expression has been detected in pancreatic cancer, its expression in liver metastases from pancreatic cancer is still unknown. In this study, overall 43 pancreatic cancer liver metastases (with matched primaries in 15/43 cases) and 57 pancreatic cancer cases without liver metastases or other distant metastases were analyzed for their expression of B7-H4 by immunohistochemistry. Survival curves and log-rank tests were used to test the association of B7-H4 expression with survival. B7-H4 was highly expressed in 28 (65.1%) of the 43 liver metastases and 9 (60.0%) of the 15 matched primary tumors. The expression of B7-H4 in liver metastases was significantly higher than in the matched primary tumors (p < 0.05). Patients with high B7-H4 expression in their primary pancreatic cancer had higher risk of developing liver metastases (p < 0.05). In univariate analysis, B7-H4 expression was significantly associated with the risk of death (p < 0.05). And the multivariate analysis identified that B7-H4 was an independent prognostic indicator (p < 0.05). Our results revealed B7-H4 to be associated with poor prognosis in patients with pancreatic cancer liver metastasis. B7-H4 may promote pancreatic cancer metastasis and was promising to be a potential prognostic indicator of pancreatic cancer.

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“…The other member, B7-H4 was also suggested to be an important risk factor in predicting cancer patient's prognosis [4, 5, 23–27]. Both the membrane and soluble forms of B7-H4 in cancer cells and in peripheral circulation, respectively, are valuable biomarkers in human cancers [28–30]. B7-H4 was also involved in the regulation of cancer cell behaviors such as proliferation, cell cycle arrest, migration and invasion.…”

Section: Discussionmentioning

confidence: 99%

Assessment of combined expression of B7-H3 and B7-H4 as prognostic marker in esophageal cancer patients

et al. 2016

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The co-stimulatory ligands of B7-family have been confirmed to play an important role in negatively regulating the T-cell mediated anti-tumor immunity. In addition, these inhibitory molecules are also aberrantly expressed on various human cancers tissues, and significantly associated with cancer progression and patients' poor prognoses. We have previously reported that B7-H3 and B7-H4 ligands are highly expressed in human esophageal cancer tissues. Herein, we tried to further analyze the value of their combined expression on prognostic prediction for esophageal cancer patients. We found that the combined expression of both B7-H3 and B7-H4 could be used as a valuable risk factor for predicting the prognosis of esophageal cancer patients (P=0.003). Moreover the status of these patients with high expression of both B7-H3 and B7-H4, was positively and significantly associated with the tumor invasion depth (P=0.0414) and TNM stage (P=0.0414). The Cox multivariate proportional hazards regression analysis revealed that the tumor size (P=0.007), the TNM stage (P=0.024) and the status of both B7-H3 and B7-H4 high expression (P=0.011), could be used as an independent risk factor for predicting patients' postoperative prognosis, respectively. In conclusion, our data indicated that the combined application of B7-H3 and B7-H4 expression can be effectively used as a prognostic marker in esophageal cancer patients.

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Diagnostic value of serum B7-H4 for hepatocellular carcinoma

Cited by 28 publications

References 25 publications

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

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

Prognostic significance of B7-H4 expression in matched primary pancreatic cancer and liver metastases

Assessment of combined expression of B7-H3 and B7-H4 as prognostic marker in esophageal cancer patients

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