Research Institute for Convergence of Biomedical Science and Technology, Pusan National Yangsan Hospital, 20, Geumo-Ro, Mulguem-Eup, Yangsan-Si, Gyeongsangnam-Do, South Korea.
Department of Pathology, Pusan National University Yangsan Hospital, 20, Geumo-Ro, Mulguem-Eup, Yangsan-Si, Gyeongsangnam-Do, South Korea.
J Ovarian Res. 2023 Jan 6;16(1):3. doi: 10.1186/s13048-022-01076-z.
B7-H4 is expressed in various types of cancers and its expression inversely correlates with the degree of tumor-infiltrating lymphocytes (TILs). Studies have shown the relationship between B7-H4, cancer stem cell (CSC) properties, and epithelial-mesenchymal transition (EMT) in various cancers. However, very few studies have investigated the relationship between B7-H4, TILs, cancer stemness, and EMT in epithelial ovarian cancer (EOC). The present study aimed to elucidate whether B7-H4 is involved in immune evasion and examine whether B7-H4 is associated with cancer stemness or EMT in ovarian serous carcinoma, the most common type of EOC. The clinical significance of B7-H4 was also investigated to evaluate its potential as a therapeutic target.
A total of 145 patients included in this study. The degree of stromal TILs was evaluated using hematoxylin and eosin (H&E)-stained slides. Immunohistochemical analysis of B7-H4, CSC-related biomarkers (CD24, CD44s, CD133, and ALDH1), and EMT-related biomarkers (E-cadherin, N-cadherin, and vimentin) was performed using tissue microarray. qRT-PCR for VTCN1, CD24, CD44, PROM1, ALDH1, CDH1, CDH2, and VIM genes was performed on 38 frozen tissue samples. The mRNA expression levels were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) online analysis tool.
B7-H4 protein expression positively correlated with the degree of stromal TILs. CD24, CD44s, and CD133 expression showed a positive correlation with B7-H4 expression at both the protein and mRNA levels, but ALDH1 correlated only at the protein level. E-cadherin expression was positively correlated with B7-H4 expression at both the protein and mRNA levels. N-cadherin and vimentin expression was inversely related to B7-H4 expression only at the mRNA level. B7-H4 positive patients were associated with higher tumor grade and lower overall survival rate than B7-H4 negative patients, especially in ovarian serous carcinoma with low stromal TILs.
The present study demonstrates that B7-H4 may not be involved in the immune evasion mechanism, but is involved in cancer stemness and mesenchymal-epithelial transition. In addition, B7-H4 may be a therapeutic target for the treatment of ovarian serous carcinoma, especially with low stromal TILs.
B7-H4 在多种癌症中表达，其表达与肿瘤浸润淋巴细胞（TILs）的程度呈负相关。研究表明，B7-H4 与癌症干细胞（CSC）特性和上皮-间充质转化（EMT）在各种癌症之间存在关系。然而，很少有研究调查 B7-H4、TILs、癌症干性和 EMT 之间在卵巢浆液性癌（EOC）中的关系。本研究旨在阐明 B7-H4 是否参与免疫逃逸，并检查 B7-H4 是否与卵巢浆液性癌中的癌症干性或 EMT 相关。还研究了 B7-H4 的临床意义，以评估其作为治疗靶点的潜力。
本研究共纳入 145 例患者。使用苏木精和伊红（H&E）染色载玻片评估基质 TILs 的程度。使用组织微阵列进行 B7-H4、CSC 相关生物标志物（CD24、CD44s、CD133 和 ALDH1）和 EMT 相关生物标志物（E-cadherin、N-cadherin 和 vimentin）的免疫组织化学分析。对 38 个冷冻组织样本进行 VTCN1、CD24、CD44、PROM1、ALDH1、CDH1、CDH2 和 VIM 基因的 qRT-PCR。使用在线分析工具 Gene Expression Profiling Interactive Analysis（GEPIA）分析基因表达水平。
B7-H4 蛋白表达与基质 TILs 的程度呈正相关。CD24、CD44s 和 CD133 的表达在蛋白和 mRNA 水平上均与 B7-H4 表达呈正相关，但 ALDH1 仅在蛋白水平上相关。E-cadherin 表达在蛋白和 mRNA 水平上均与 B7-H4 表达呈正相关。N-cadherin 和 vimentin 表达仅在 mRNA 水平上与 B7-H4 表达呈负相关。与 B7-H4 阴性患者相比，B7-H4 阳性患者的肿瘤分级更高，总生存率更低，尤其是在低基质 TILs 的卵巢浆液性癌中。
本研究表明，B7-H4 可能不参与免疫逃逸机制，但参与癌症干性和间充质-上皮转化。此外，B7-H4 可能是治疗卵巢浆液性癌，尤其是低基质 TILs 的治疗靶点。
