PO.TB10.16 · 肿瘤生物学
癌细胞中的 TGF-beta 异质性可能与胃癌的肿瘤进展相关
TGF-beta heterogeneity in cancer cells might be associated with tumor progression in gastric cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：据报道，肿瘤异质性常见于多种类型的人类癌症。肿瘤异质性不仅可能存在于人类肿瘤中，也可能存在于癌细胞系中。分析肿瘤异质性可能有助于理解肿瘤发生发展的机制。在本研究中，我们使用一种胃癌细胞系和人胃肿瘤样本检测了胃癌的异质性。
材料与方法：本研究使用了胃癌细胞系 OCUM-12 和共 530 例胃癌。通过有限稀释法对 OCUM-12 细胞进行亚克隆后，检测了细胞系的异质性。通过 RT-PCR 检测每个亚克隆细胞中 TGF-β1 和 TGF-β2 的 mRNA 表达水平。接下来，我们使用 530 例胃癌标本进行了 TGF-β 的免疫组化研究。在癌细胞和癌相关成纤维细胞（CAF）中均评估了 TGF-β 表达。免疫组化染色水平不仅通过人工评估，还使用数字化 QuPath 评估。分析了 TGF-β1 表达与临床病理特征之间的相关性。
结果：TGF-β1 和 TGF-β2 的 mRNA 表达水平在 12 个 OCUM-12 亚克隆之间存在差异。TGF-beta 的免疫组化染色水平在不同肿瘤标本之间也存在差异。在 2 期中，高 TGF-beta 表达组的 5 年无复发生存率倾向于预后不良（p = 0.0913），而在 3 期中，该生存率则显示出较好的预后。
结论：癌细胞中的 TGF-beta 异质性可能与胃癌的肿瘤进展相关。
查看英文原文 English abstract
Background: It has been reported that tumor heterogeneity is frequently found in various types of human carcinomas. Tumor heterogeneity may exist in not only human tumors but also cancer cell lines. Analysis of tumor heterogeneity might be useful to understand the mechanisms of tumor development. In this study, we examined the heterogeneity of gastric cancer using a gastric cancer cell line and human gastric tumor samples.
Materials and Methods: A gastric cancer cell line OCUM-12 and a total of 530 gastric cancers were used in this study. The heterogeneity of cancer cell line was examined after subcloning of OCUM-12 cells using limiting dilution. mRNA expression levels of TGF-ꞵ1 and TGF-ꞵ2 in each subclone cell were examined by RT-PCR. Next, we performed immunohistochemical study of TGF-ꞵ using 530 gastric cancers specimens. TGF-ꞵ expression was evaluated both at cancer cells and at cancer-associated fibroblasts (CAFs). Immunohistochemical staining level was evaluated by not only manual but also using digital QuPath. Correlation between TGF-ꞵ1 expression and clinicopathological features were analyzed.
Results: mRNA expression levels of TGF-ꞵ1 and TGF-ꞵ2 was different among 12 OCUM-12 subclones. Immunohistochemical staining level of TGF-beta was also different among tumor specimens. Five-year recurrence-free survival rate of high TGF-beta expression group tended to be a poor prognosis (p = 0.0913) in Stage 2, while the survival rate showed a better prognosis in Stage 3.
Conclusion: TGF-beta heterogeneity in cancer cells might be associated with tumor progression in gastric cancer.
利益披露 Disclosure
D. Imanishi,
Grants-in-Aid for Scientific Research ).
M. Yashiro,
Grants-in-Aid for Scientific Research ).
H. Nishikubo, None..
T. Sano, None..
D. Ma, None..
C. Fan, None..
T. Sakuma, None.
Y. Yamamoto,
Grants-in-Aid for Scientific Research ).
K. Maeda, None.