UbcH10 expression can predict prognosis and sensitivity to the antineoplastic treatment for colorectal cancer patients
UbcH10 expression can predict prognosis and sensitivity to the antineoplastic treatment for colorectal cancer patients
复制标题
DOI：
10.1002/mc.22322
复制
发表时间：
2016-05-01
影响因子：
4.6
通讯作者：
Pallante, Pierlorenzo
中科院分区：
文献类型：
--
作者：
Cacciola, Nunzio Antonio;Calabrese, Chiara;Pallante, Pierlorenzo
结直肠癌（Colorectal cancer，CRC）是世界范围内最常见、最致命的恶性肿瘤之一。尽管在诊断和治疗方面取得了进展，但肿瘤标志物的鉴定仍然是一个强烈的临床需求，因为目前的治疗仅在一个亚组的患者中有效。UbcH 10是一种潜在的候选生物标志物，其表达水平可用于预测对化疗或靶向药物的反应或耐药性。UbcH 10 mRNA和蛋白表达水平已在一个大的CRC患者组中进行了评估，并与临床病理特征，包括KRAS突变。此外，UbcH 10的内源性水平及其对细胞生长的作用已经在CRC细胞中进行了评估。最后，为了研究UbcH 10蛋白表达对伊立替康、其活性代谢产物SN-38和西妥昔单抗治疗的反应的影响，在两种结肠癌细胞系Caco-2和DLD 1上进行了UbcH 10沉默实验。在分析的绝大多数患者中观察到UbcH 10 mRNA和蛋白的过表达。UbcH 10抑制降低了CRC细胞生长速率（至少部分通过细胞周期蛋白B和ERK 1的失调），并使其对伊立替康、SN-38和西妥昔单抗的药物治疗敏感（至少部分通过AKT的下调）。总之，这些发现表明UbcH 10表达调节CRC生长，并可能在CRC患者的个性化治疗中发挥重要作用。(c)2015 Wiley Periodicals，Inc.
Colorectal cancer (CRC) is one of the most frequent and deadly malignancies worldwide. Despite the progresses made in diagnosis and treatment, the identification of tumor markers is still a strong clinical need, because current treatments are efficacious only in a subgroup of patients. UbcH10 represents a potential candidate biomarker, whose expression levels could be employed to predict response or resistance to chemotherapy or targeted agents. UbcH10 mRNA and protein expression levels have been evaluated in a large group of CRC patients and correlated with clinico-pathological characteristics, including KRAS mutations. Moreover, the endogenous levels of UbcH10 and its role on cell growth have been evaluated in CRC cells. Finally, to investigate the impact of UbcH10 protein expression on the response to irinotecan, its active metabolite SN-38 and cetuximab treatment, UbcH10 silencing experiments were carried-out on two colon carcinoma cell lines, Caco-2, and DLD1. Overexpression of UbcH10 mRNA and protein was observed in the vast majority of patients analyzed. UbcH10 suppression decreased CRC cell growth rate (at least in part through deregulation of Cyclin B and ERK1) and sensitized them to pharmacological treatments with irinotecan, SN-38 and cetuximab (at least in part through a down-regulation of AKT). Taken together, these findings indicate that UbcH10 expression regulates CRC growth and could play an important role in the personalization of the therapy of CRC patients. (c) 2015 Wiley Periodicals, Inc.