Jiang Wen G, Watkins Gareth, Douglas-Jones Anthony, Mokbel Kefah, Mansel Robert E, Fodstad Oystein
Metastasis & Angiogenesis Research Group, Wales College of Medicine, Cardiff University, Cardiff, United Kingdom.
Int J Cancer. 2005 Dec 10;117(5):730-7. doi: 10.1002/ijc.21221.
Com-1 is a recently discovered molecule that has putative action on the metastatic nature of cancer cells. The molecular action and clinical implication in cancer and prognosis are yet to be established. The current study examined the role of Com-1 in a cohort of patients with breast cancer, with particular emphasis on its relationship with clinical outcomes and ER status. A panel of human breast cancer cell lines were tested. A cohort of breast cancer tumours (n-120) with matched normal non-neoplastic mammary tissues (n = 32) were used. Expression of Com-1 in cancer cells and mammary tissues were studied using conventional and real-time quantitative PCR. Expression profile was analysed against clinical information including tumour grade, staging, nodal status, ER status and survival of the patients. Statistical analysis was Mann-Whitney U-test and Cox Proportion analysis. Com-1 was expressed in breast cancer cell lines. Com-1 protein staining was primarily found in nucleus of epithelial cells of mammary tissues. Tumour cells in breast tissues exhibited a significant reduction in nuclear staining of Com-1, compared to normal epithelial cells (p = 0.0061). Breast tumour tissues expressed similar levels of Com-1, compared to normal non-neoplastic mammary tissues (p = 0.62). There was, however, a stepwise decrease in tumours from patients with predicted good, moderate, to poor prognosis (using Nottingham Prognostic Index) (166 +/- 135 copies of Com1 transcript, 44.3 +/- 36 and 0.64 +/- 0.24, respectively, p = 0.06 by Kruskal-Wallis test). Likewise, node positive tumours had low levels of Com-1, compared to node negative tumours. Tumours from patients who developed metastasis (11.4 +/- 7 copies of Com1 transcript), had local recurrence (41.5 +/- 3.7 copies of Com1 transcript), or who died of breast cancer (0.058 +/- 0.03 copies of Com1 transcript) had lower levels of Com-1, when compared to tumours from patients who remained disease free (156 +/- 129 copies of Com1 transcript). There was no significant correlation between Com-1 and overall survival or disease free survival. When ER status were taken into consideration, it was demonstrated that low levels of Com-1 in ER-beta positive tumours were highly correlated with shorter overall survival of the patients (p = 0.018) (median follow-up 120 months). Com-1 is a nuclear protein, whose expression is reduced in human breast cancer tissues and cancer cell lines. The loss of Com-1 protein is primarily from the nuclear compartment in cancer cells. The expression levels of Com-1 in breast tumours are correlated with the prognosis of the patients and with the long term overall survival in association with ER status.
Com-1是一种最近发现的分子，对癌细胞的转移特性具有假定作用。其在癌症中的分子作用、临床意义及预后尚待确定。本研究调查了Com-1在一组乳腺癌患者中的作用，特别关注其与临床结局及雌激素受体（ER）状态的关系。对一组人乳腺癌细胞系进行了检测。使用了一组乳腺癌肿瘤（n = 120）及匹配的正常非肿瘤性乳腺组织（n = 32）。采用传统和实时定量PCR研究Com-1在癌细胞和乳腺组织中的表达。根据包括肿瘤分级、分期、淋巴结状态、ER状态及患者生存情况等临床信息分析表达谱。统计分析采用曼-惠特尼U检验和Cox比例分析。Com-1在乳腺癌细胞系中表达。Com-1蛋白染色主要见于乳腺组织上皮细胞的细胞核。与正常上皮细胞相比，乳腺组织中的肿瘤细胞Com-1核染色显著减少（p = 0.0061）。与正常非肿瘤性乳腺组织相比，乳腺肿瘤组织中Com-1表达水平相似（p = 0.62）。然而，根据诺丁汉预后指数预测，预后良好、中等及较差的患者肿瘤中Com-1呈逐步下降趋势（Com1转录本分别为166±135拷贝、44.3±36拷贝和0.64±0.24拷贝，Kruskal-Wallis检验p = 0.06）。同样，淋巴结阳性肿瘤的Com-1水平低于淋巴结阴性肿瘤。与无疾病复发患者的肿瘤相比，发生转移（Com1转录本11.4±7拷贝）、局部复发（Com1转录本41.5±3.7拷贝）或死于乳腺癌（Com1转录本0.058±0.03拷贝）患者的肿瘤中Com-1水平较低。Com-1与总生存期或无病生存期之间无显著相关性。当考虑ER状态时，发现ER-β阳性肿瘤中Com-1水平低与患者较短的总生存期高度相关（p = 0.018）（中位随访120个月）。Com-1是一种核蛋白，其在人乳腺癌组织和癌细胞系中的表达降低。Com-1蛋白的缺失主要发生在癌细胞的核区室。乳腺肿瘤中Com-1的表达水平与患者预后及与ER状态相关的长期总生存期相关。
