The human epididymis protein 4 acts as a prognostic factor and promotes progression of gastric cancer.

Human epididymis protein 4 (HE4), represented as an epididymis-specific gene and designated a WAP four-disulfide core domain protein 2 (WFDC2), is amplified in many tumors. However, little is known about its clinical significance and biological function in gastric carcinomas. We found that HE4 was more commonly observed in gastric carcinoma tissues than in normal tissues and was significantly correlated with Lauren classification, TNM stage, and tumor size by immunohistochemistry. The overall survival rate of patients with HE4 low expression was significantly higher than that of the patients with HE4 high expression. In addition, silencing of HE4 expression inhibits cell proliferation and migration and enhances cell apoptosis. Subsequent studies reveal that the Src, Akt, and Erk1/2 signaling may be involved with pro-survival and anti-apoptotic effects of the HE4 on gastric cancer cells. Taken together, this study provides new evidence on promotive effects of the HE4 on gastric cancer progression and indicates that HE4 might be a promising prognostic factor for gastric cancer diagnosis.

Clinicopathological analysis of PD-L2 expression in colorectal cancer.

BACKGROUND: (PD-L2), a ligand of programmed cell death protein 1 (PD-1), is an inhibitory receptor of T cells and activated B cells. Many studies have focused on PD-L1, another ligand of PD-1, and the prognostic significance of PD-L1 has been reported in many tumors. However, the expression of PD-L2 in relation to clinical outcomes has not been fully investigated in cancer patients. PATIENTS AND METHODS: In this study, we investigated the expression of PD-L2 via immunohistochemistry (IHC) in the pathological specimens of 348 patients treated for colorectal cancer (CRC). RESULTS: Strong PD-L2 expression was found in the cancer tissues from 41% of the CRC patients who also had a high TNM stage and carcinoembryonic antigen (CEA) concentration. We also carried out functional studies in vitro, which showed that PD-L2 did not influence the growth of the CRC cell line HCT116, but increased cell invasion. CONCLUSION: Collectively, these findings suggest that PD-L2 may be a potential therapeutic target for CRC.

B7-H3 expression in breast cancer and upregulation of VEGF through gene silence.

B7-H3, a novel member of the B7 family, was previously known as a regulatory ligand regulating T-cell-mediated immune response, and in recent years it was found to take a significant role in various cancers. In some tumor types, high expression of B7-H3 had been linked to a poor prognosis, whereas in other cancers the opposite effect had been observed. The precise role of B7-H3 in tumor immunity is unclear, and further investigations are needed. In the present study, we studied the expression of B7-H3 in the pathologic specimens of 221 patients treated for breast cancer by immunohistochemistry. Strong B7-H3 expression was found in cancer tissues from 80.55% patients, and B7-H3 expression had a negative relation with vascular endothelial growth factor (VEGF) expression, microvascular density for CD34, and tumor size. Furthermore, through lipopolysaccharide-mediated delivery of stable short hairpin ribonucleic acid we observed that silencing of B7-H3 could increase the transcription and secreting of VEGF in breast cancer cell line MCF-7. In summary, the present study demonstrated that B7-H3 suppressed tumor growth through inhibiting VEGF expression. These results increased knowledge of the nonimmunological role of B7-H3 protein and provided novel insights into great biological functions and a putative therapeutic target in breast cancer.

Clinical significance of the induction of macrophage differentiation by the costimulatory molecule B7-H3 in human non-small cell lung cancer.

B7-H3, a member of the B7 family of molecules, is expressed in certain types of human cancer and is important in tumor development and progression. Although several studies have reported that the expression of B7-H3 is correlated with poor outcomes in patients with cancer, its exact role in cancer remains unknown. In the present study, the expression levels of B7-H3 in the pathological specimens of 105 patients treated for non-small cell lung cancer (NSCLC) were examined by immunohistochemistry. A high expression level of B7-H3 was observed in 46.9% of the 105 NSCLC tissue specimens. These patients demonstrated a more advanced tumor grade and a shorter survival time. In addition, we also examined the levels of tumor-associated macrophages (TAMs) in NSCLC tissues and observed that the levels were positively correlated with the expression of B7-H3, and that higher levels of macrophages were associated with lower levels of infiltrating T cells and a shorter survival time. These results demonstrated that TAMs are important in the evasion of tumor immune surveillance in NSCLC. Furthermore, through knockdown of B7-H3 by RNA interference, we observed that soluble B7-H3 was capable of inducing macrophages to express higher levels of macrophage mannose receptor (MMR) and lower levels of human leukocyte antigen (HLA)-DR, as well as higher levels of interleukin-10 (IL-10) and lower levels of IL-1ß in vitro. These observations are characteristic of an anti-inflammatory/reparatory (alternative/M2) phenotype. Therefore, our data suggests that B7-H3 proteins are involved in the progression of NSCLC by inducing the development of monocytes into anti-inflammatory cells.