CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：The stromal tumor-infiltrating lymphocytes, cancer stemness, epithelial-mesenchymal transition, and B7-H4 expression in ovarian serous carcinoma.
The stromal tumor-infiltrating lymphocytes, cancer stemness, epithelial-mesenchymal transition, and B7-H4 expression in ovarian serous carcinoma.
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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的治疗靶点，尤其是在基质 TILs 较低的情况下。
B7-H4在多种癌症中表达，其表达与TIL（肿瘤浸润淋巴细胞）（TILs）的程度呈负相关。研究表明，B7-H4、癌症干细胞（CSC）特性及上皮-间质转化（EMT）在多种癌症中存在关联。然而，很少有研究探讨B7-H4、TILs、癌症干性及EMT在上皮性卵巢癌（EOC）中的关系。本研究旨在阐明B7-H4是否参与免疫逃逸，并检验B7-H4是否与卵巢浆液性癌（EOC中最常见的类型）中的癌症干性或EMT相关。同时研究了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。采用苏木精-伊红（H&E）染色切片评估间质TILs的程度。使用组织芯片对B7-H4、CSC相关生物标志物（CD24、CD44s、CD133和ALDH1）以及EMT相关生物标志物（E-cadherin、N-cadherin和vimentin）进行免疫组化分析。对38份冷冻组织样本进行VTCN1、CD24、CD44、PROM1、ALDH1、CDH1、CDH2和VIM基因的qRT-PCR检测。使用基因表达谱交互分析（GEPIA）在线分析工具分析mRNA表达水平。
B7-H4蛋白表达与间质TILs程度呈正相关。CD24、CD44s和CD133表达在蛋白和mRNA水平均与B7-H4表达呈正相关，但ALDH1仅在蛋白水平相关。E-cadherin表达在蛋白和mRNA水平均与B7-H4表达呈正相关。N-cadherin和vimentin表达仅在mRNA水平与B7-H4表达呈负相关。B7-H4阳性患者与B7-H4阴性患者相比，与更高的肿瘤分级和更低的总生存率相关，尤其是在间质TILs低的卵巢浆液性癌中。
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.
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