RINF (CXXC5) is overexpressed in solid tumors and is an unfavorable prognostic factor in breast cancer†
RINF (CXXC5) is overexpressed in solid tumors and is an unfavorable prognostic factor in breast cancer†
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DOI：
10.1093/annonc/mdq737
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发表时间：
2011-10-01
影响因子：
50.5
通讯作者：
Pendino, F.
中科院分区：
文献类型：
--
作者：
Knappskog, S.;Myklebust, L. M.;Pendino, F.
背景资料：我们以前曾描述过类维生素A诱导核因子（RINF）在造血细胞分化过程中的重要作用，并认为它可能参与髓性白血病和白血病前期。在这里，我们研究了该基因是否可以在恶性组织中与其正常组织来源相比具有失调表达，以及这种潜在的失调是否与重要的临床病理参数相关。在局部晚期乳腺肿瘤，转移性恶性黑色素瘤，和乳头状甲状腺癌，并与其配对或非配对的正常参考样品进行比较。结果：与正常对照组织相比，RINF在所有肿瘤组织（原发性乳腺癌、甲状腺癌和转移性黑色素瘤）中的表达均显著增高（P < 0.001）。重要的是，高水平的RINF表达与乳腺癌的总生存率相关（P = 0.013）。这一发现在三个独立的公共微阵列数据集中得到证实（P = 0.043，n = 234; P = 0.016，n = 69; P = 0.001，n = 196），并且与他莫昔芬治疗无关。值得注意的是，高水平的RINF与TP 53野生型状态密切相关。（P = 0.002）可能表明在某些乳腺癌的恶性发展过程中，高水平的RINF可以替代TP 53突变作为致癌机制。我们的数据表明：（i）RINF过表达与实体瘤的恶性表型有关，（ii）RINF过表达是乳腺肿瘤预后不良的一个独立分子标志。
Background: We have previously described the essential role of the retinoid-inducible nuclear factor (RINF) during differentiation of hematopoietic cells and suggested its putative involvement in myeloid leukemia and preleukemia. Here, we have investigated whether this gene could have a deregulated expression in malignant tissues compared with their normal tissues of origin and if this potential deregulation could be associated with important clinicopathological parameters.Patients and methods: RINF messenger RNA expression was examined in biopsies from locally advanced breast tumors, metastatic malignant melanomas, and papillary thyroid carcinomas and compared with their paired or nonpaired normal reference samples. Further, the prognostic role of RINF expression was evaluated in locally advanced breast cancer.Results: RINF expression was significantly higher in all tumor forms (primary breast, and thyroid cancers and metastatic melanomas) as compared with normal control tissues (P < 0.001 for each comparison). Importantly, high levels of RINF expression correlated to a poor overall survival in breast cancer (P = 0.013). This finding was confirmed in three independent public microarray datasets (P = 0.043, n = 234; P = 0.016, n = 69; P = 0.001, n = 196) and was independent of tamoxifen therapy. Notably, high levels of RINF was strongly associated with TP53 wild-type status (P = 0.002) possibly indicating that high levels of RINF could substitute for TP53 mutations as an oncogenic mechanism during the malignant development of some cases of breast cancer.Conclusions: Our data indicate that (i) RINF overexpression is associated with the malignant phenotype in solid tumors and (ii) RINF overexpression represents an independent molecular marker for poor prognosis in breast tumors.