Danish Centre for Translational Breast Cancer Research (DCTB), Strandboulevarden 49, Copenhagen, Denmark.
J Proteome Res. 2010 Aug 6;9(8):3941-53. doi: 10.1021/pr100160u.
Breast cancer is the leading cause of cancer deaths in women today and is the most common cancer (excluding skin cancers) among women in the Western world. Although cancers detected by screening mammography are significantly smaller than nonscreening ones, noninvasive biomarkers for detection of breast cancer as early as possible are an urgent need as the risk of recurrence and subsequent death is closely related to the stage of the disease at the time of primary surgery. A set of 123 primary breast tumors and matched normal tissue was analyzed by two-dimensional (2D) gel electrophoresis, and a novel protein, C7orf24, was identified as being upregulated in cancer cells. Protein expression levels of C7orf24 were evaluated by immunohistochemical assays to qualify deregulation of this protein. Analysis of C7orf24 expression showed up-regulation in 36.4 and 23.4% of cases present in the discovery sample set (123 samples) and in an independent large TMA validation data set (2197 samples) of clinically annotated breast cancer specimens, respectively. Survival analysis showed that C7orf24 overexpression defines a subgroup of breast tumors with poor clinical outcome. Up-regulation of C7orf24 was also found in other cancer types. Four of these were investigated in greater detail, and we found that a proportion of tumors (58% in cervical, 38% in lung, 72% in colon, and 46% in breast cancer) expressed C7orf24 at levels exceeding those seen in normal samples. The observed overexpression of this protein in different types of cancer suggests deregulation of C7orf24 to be a general event in epithelial carcinogenesis, indicating that this protein may play an important role in cancer cell biology and thus constitute a novel therapeutic target. Furthermore, as C7orf24 is externalized to the tissue extracellular fluid and can be detected in serum, this protein also represents a potential serological marker.
乳腺癌是当今女性癌症死亡的主要原因，也是西方女性中最常见的癌症（不包括皮肤癌）。虽然通过筛查性乳房 X 光检查发现的癌症明显小于非筛查性癌症，但迫切需要非侵入性生物标志物来尽早检测乳腺癌，因为复发和随后死亡的风险与原发性手术时疾病的阶段密切相关。通过二维（2D）凝胶电泳分析了 123 个原发性乳腺癌肿瘤和匹配的正常组织，发现一种新型蛋白质 C7orf24 在癌细胞中上调。通过免疫组织化学检测评估 C7orf24 的蛋白表达水平，以确定该蛋白的失调情况。分析 C7orf24 的表达显示，在发现样本集中的 123 个样本（36.4%）和独立的大型 TMA 验证数据集中（2197 个样本）的临床注释乳腺癌标本中，分别有 23.4%的病例存在上调。生存分析表明，C7orf24 过表达定义了一组具有不良临床结局的乳腺癌肿瘤。C7orf24 的上调也在其他癌症类型中发现。其中 4 种进行了更详细的研究，我们发现一部分肿瘤（宫颈癌中的 58%，肺癌中的 38%，结肠癌中的 72%和乳腺癌中的 46%）的表达水平超过了正常样本。该蛋白在不同类型癌症中的过表达表明 C7orf24 的失调是上皮癌发生的普遍事件，表明该蛋白可能在癌细胞生物学中发挥重要作用，因此构成了一个新的治疗靶标。此外，由于 C7orf24 被外化到组织细胞外液中并且可以在血清中检测到，因此该蛋白也代表了一种潜在的血清标志物。
