Cai Feng-Feng, Xu Cheng, Pan Xin, Cai Lu, Lin Xiao-Yan, Chen Su, Biskup Ewelina
Department of Breast Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, PR China.
Department of Central Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai, PR China.
Oncotarget. 2016 Nov 22;7(47):77793-77806. doi: 10.18632/oncotarget.12796.
Cellular adaptive mechanisms are crucial for tumorigenesis and a common feature in solid tumor progression. Hypoxia-inducible factor-1α (HIF-1α) facilitates the biological response to hypoxia, advancing angiogenesis and metastatic potential of the tumor. The peroxisome proliferator-activated receptor γ coactivators 1α (PGC-1α) enhances mitochondrial biogenesis, favored by migratory/invasive cancer cells. We conducted a prospective, long-term follow up study to determine whether HIF-1α and PGC-1α can be implemented as predictive biomarker in breast cancer. HIF-1α and PGC-1α plasma concentrations were measured in patients and in healthy controls by enzyme linked immune sorbent assay. Breast cancer patients had significantly higher HIF-1α and PGC-1α levels, which correlated with clinicopathological features, overall with more aggressive cancer characteristics. Disease free and overall survival of breast cancer patients with high HIF-1α and PGC-1α were significantly poorer than in patients with low plasma levels. In multivariate analysis, high amount of PGC-1α showed independent prognostic value. Our data suggests that HIF-1α and PGC-1α may be promising, noninvasive, biomarkers with a high potential for future clinical implication to identify subgroups of patients with poorer prognosis and to indicate early, subclinical metastasis.
细胞适应性机制对肿瘤发生至关重要，是实体瘤进展的一个共同特征。缺氧诱导因子-1α（HIF-1α）促进对缺氧的生物学反应，促进肿瘤的血管生成和转移潜能。过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）增强线粒体生物合成，这受到迁移/侵袭性癌细胞的青睐。我们进行了一项前瞻性长期随访研究，以确定HIF-1α和PGC-1α是否可作为乳腺癌的预测生物标志物。通过酶联免疫吸附测定法测量患者和健康对照者血浆中HIF-1α和PGC-1α的浓度。乳腺癌患者的HIF-1α和PGC-1α水平显著更高，这与临床病理特征相关，总体上具有更具侵袭性的癌症特征。HIF-1α和PGC-1α水平高的乳腺癌患者的无病生存期和总生存期明显比血浆水平低的患者差。在多变量分析中，高量的PGC-1α显示出独立的预后价值。我们的数据表明，HIF-1α和PGC-1α可能是有前景的、非侵入性的生物标志物，具有很高的未来临床应用潜力，可用于识别预后较差的患者亚组，并指示早期亚临床转移。
