Chu Pei-Yi, Wang Shin-Mae, Chen Po-Ming, Tang Feng-Yao, Chiang En-Pei Isabel
School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei 242, Taiwan.
Department of Pathology, Show Chwan Memorial Hospital, Changhua 500, Taiwan.
J Clin Med. 2020 Sep 29;9(10):3153. doi: 10.3390/jcm9103153.
(1) Background: Tumor hypoxia leads to metastasis and certain immune responses, and interferes with normal biological functions. It also affects glucose intake, down-regulates oxidative phosphorylation, and inhibits fatty-acid desaturation regulated by hypoxia-inducible factor 1α (HIF-1α). Although tumor hypoxia has been found to promote tumor metastasis, the roles of HIF-1α-regulated genes and their application are not completely integrated in clinical practice. (2) Methods: We examined the correlation between HIF-1α, metadherin (MTDH), and interleukin (IL)-10 mRNA expression, as well as their expression patterns in the prognosis of breast cancer using the Gene Expression Profiling Interactive Analysis (GEPIA) databases via a web interface; tissue microarrays (TMAs) were stained for MTDH and IL-10 protein expression using immunohistochemistry. (3) Results: HIF-1α, MTDH, and IL-10 mRNA expression are highly correlated and strongly associated with poor prognosis. MTDH and IL-10 protein expression of breast cancer patients usually harbored negative estrogen receptor (ER) or progesterone receptor (PR) status, and late-stage tumors have higher IL-10 expression. With regard to MTDH and IL-10 protein expression status for using univariate and multivariate analysis, the results showed that the protein expression of MTDH and IL-10 in ER-negative or PR-negative breast cancer patients have the worse prognosis. (4) Conclusions: we propose a new insight into hypoxia tumors in the metabolism and immune evidence for breast cancer therapy.
(1) 背景:肿瘤缺氧会导致转移和特定免疫反应,并干扰正常生物学功能。它还会影响葡萄糖摄取,下调氧化磷酸化,并抑制由缺氧诱导因子1α(HIF-1α)调节的脂肪酸去饱和作用。尽管已发现肿瘤缺氧会促进肿瘤转移,但HIF-1α调节基因的作用及其应用在临床实践中尚未完全整合。(2) 方法:我们通过网络界面使用基因表达谱交互分析(GEPIA)数据库检查了HIF-1α、黏附素(MTDH)和白细胞介素(IL)-10 mRNA表达之间的相关性,以及它们在乳腺癌预后中的表达模式;使用免疫组织化学对组织微阵列(TMA)进行MTDH和IL-10蛋白表达染色。(3) 结果:HIF-1α、MTDH和IL-10 mRNA表达高度相关,且与不良预后密切相关。乳腺癌患者的MTDH和IL-10蛋白表达通常与雌激素受体(ER)或孕激素受体(PR)状态阴性有关,晚期肿瘤的IL-10表达更高。关于使用单变量和多变量分析的MTDH和IL-10蛋白表达状态,结果表明,ER阴性或PR阴性乳腺癌患者中MTDH和IL-10的蛋白表达预后较差。(4) 结论:我们为乳腺癌治疗中的缺氧肿瘤代谢和免疫证据提出了新的见解。