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首页> 外文期刊>American Journal of Cancer Research >Inverse association of rab31 and mucin-1 (CA15-3) antigen levels in estrogen receptor-positive (ER+) breast cancer tissues with clinicopathological parameters and patients’ prognosis
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Inverse association of rab31 and mucin-1 (CA15-3) antigen levels in estrogen receptor-positive (ER+) breast cancer tissues with clinicopathological parameters and patients’ prognosis

机译：雌激素受体阳性（ER +）乳腺癌组织中rab31和mucin-1（CA15-3）抗原水平与临床病理参数和患者预后呈负相关

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摘要

Dysregulated expression of rab31, a member of the large Rab protein family of the Ras superfamily of small GTPases, has been observed in several types of cancer, including breast cancer. Rab31, depending on its expression level, may regulate the switch between an invasive versus proliferative phenotype of breast cancer cells in vitro. Moreover, gene expression of rab31 is induced by the C-terminal subunit of mucin-1 (MUC1-C) and estrogen receptors (ER). To gain further insights into the clinical relevance of rab31 and mucin-1 expression in breast cancer, we analyzed the relation between rab31 and mucin-1 (CA15-3) antigen levels in detergent tissue extracts of ER-positive (ER+) tumors and clinicopathological parameters as well as patients’ prognosis. No significant correlation was observed between rab31 and CA15-3 antigen levels. Elevated rab31 antigen levels in tumor tissue extracts were significantly associated with higher tumor grade (P = 0.021). Strikingly, an inverse significant association was observed for CA15-3 with tumor grade (P = 0.032). Furthermore, high rab31 antigen levels were significantly associated with a high S-phase fraction (SPF, P = 0.047), whereas a trend for lower CA15-3 antigen levels in tumor tissue displaying higher SPF was observed. High rab31 antigen levels were significantly associated with poor 5-year disease-free survival (DFS) of ER+ breast cancer patients in univariate Cox regression analysis (HR = 1.91, 95% CI = 1.14-3.17, P = 0.013). In contrast, high levels of CA15-3 antigen levels were associated with better patients’ prognosis (HR = 0.56, 95% CI = 0.33-0.95, P = 0.031). In multivariable analysis, rab31 antigen levels contributed independent prognostic information for DFS when adjusted for prognostically relevant clinicopathological parameters with a HR for high versus low values of 1.97 (95% CI = 1.09-3.54, P = 0.024), whereas CA15-3 antigen levels were not significant. Our results strongly suggest that rab31 antigen levels in tumor tissue are associated with the proliferative status, and rab31 represents an independent biomarker for prognosis in ER+ breast cancer patients. Total mucin-1 (CA 15-3) levels are rather inversely associated with tumor grade and SPF, and elevated levels even indicate prolonged DFS in ER+ breast cancer patients.
机译：在一些类型的癌症（包括乳腺癌）中已观察到rab31的表达失调，而rab31是小型GTPases的Ras超家族的大Rab蛋白家族的成员。 Rab31取决于其表达水平，可以调节体外乳腺癌细胞的侵袭性和增殖表型之间的转换。此外，rab31的基因表达是由粘蛋白1（MUC1-C）和雌激素受体（ER）的C末端亚基诱导的。为了进一步了解rab31和mucin-1在乳腺癌中的临床相关性，我们分析了ER阳性（ER +）肿瘤清洁组织提取物中rab31和mucin-1（CA15-3）抗原水平之间的关系以及临床病理参数以及患者的预后。在rab31和CA15-3抗原水平之间未观察到显着相关性。肿瘤组织提取物中的rab31抗原水平升高与更高的肿瘤等级显着相关（P = 0.021）。令人惊讶的是，观察到CA15-3与肿瘤等级呈负显着负相关（P = 0.032）。此外，高的rab31抗原水平与高的S期分数显着相关（SPF，P = 0.047），而在显示更高SPF的肿瘤组织中观察到CA15-3抗原水平降低的趋势。在单变量Cox回归分析中，高rab31抗原水平与ER +乳腺癌患者的5年无病生存期差（DFS）显着相关（HR = 1.91，95％CI = 1.14-3.17，P = 0.013）。相反，高水平的CA15-3抗原与更好的患者预后相关（HR = 0.56，95％CI = 0.33-0.95，P = 0.031）。在多变量分析中，当针对预后相关的临床病理参数进行调整时，rab31抗原水平为DFS贡献了独立的预后信息，HR的高/低值为1.97（95％CI = 1.09-3.54，P = 0.024），而CA15-3抗原水平不重要。我们的结果强烈表明，肿瘤组织中的rab31抗原水平与增殖状态相关，而rab31代表ER +乳腺癌患者预后的独立生物标志物。总粘蛋白1（CA 15-3）水平与肿瘤等级和SPF呈负相关，并且水平升高甚至表明ER +乳腺癌患者的DFS延长。

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