Overexpression of SULT2B1b is an independent prognostic indicator and promotes cell growth and invasion in colorectal carcinoma.
Overexpression of SULT2B1b is an independent prognostic indicator and promotes cell growth and invasion in colorectal carcinoma.
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SULT2B1b的过度表达是结直肠癌的独立预后指标并促进细胞生长和侵袭
DOI：
10.1038/labinvest.2015.84
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Gao CF
中科院分区：
文献类型：
--
作者：
Hu L;Yang GZ;Zhang Y;Feng D;Zhai YX;Gong H;Qi CY;Fu H;Ye MM;Cai QP;Gao CF
细胞溶质磺基转移酶2B 1b（SULT 2B 1b）的异常表达已在几种人类恶性肿瘤中报道。然而，SULT 2B 1b在结直肠癌（CRC）中的表达模式和临床意义尚不清楚。实时定量PCR、蛋白质印迹和免疫组织化学分析用于确定CRC临床样本和CRC衍生细胞系中SULT 2B 1b的表达。Kaplan-Meier和考克斯比例回归分析用于评估SULT 2B 1 b表达与两个独立队列485例CRC患者生存期之间的相关性。采用获得和丧失功能的方法来研究SULT 2B 1b在调节CRC细胞生长和侵袭中的作用。我们发现SULT 2B 1b表达在CRC临床样本和CRC衍生细胞系中频繁上调，并且在训练和验证队列中与淋巴结转移和TNM分期显著相关。肿瘤内SULT 2B 1b表达较高的患者的疾病特异性生存期（DSS）和无病生存期（DFS）明显短于表达较低的患者。重要的是，SULT 2B 1b表达增加显著预测DSS和DFS较差，并且是两个队列中II期患者的独立不利预后指标。功能研究表明，SULT 2B 1b的过表达促进CRC细胞的生长和体外侵袭。相反，SULT 2B 1b的敲低抑制了这些过程。总之，我们的研究结果表明SULT 2B 1b表达与疾病进展和转移相关，并可能作为CRC患者的新型预后生物标志物和潜在治疗靶点。
Aberrant expression of cytosolic sulfotransferase 2B1b (SULT2B1b) has been reported in several human malignancies. However, the expression pattern and clinical significance of SULT2B1b in colorectal carcinoma (CRC) remains unknown. Real-time quantitative PCR, western blot, and immunohistochemistry analyses were used to determine SULT2B1b expression in CRC clinical samples and CRC-derived cell lines. Kaplan–Meier and Cox proportional regression analyses were used to evaluate the association between SULT2B1b expression and patient survival in two independent cohorts of 485 patients with CRC. Gain- and loss-of-function approaches were employed to investigate the role of SULT2B1b in regulation of CRC cell growth and invasion. We found that SULT2B1b expression was frequently upregulated in CRC clinical samples and CRC-derived cell lines and was significantly correlated with lymph node metastasis and TNM stage in both the training and validation cohorts. Patients with higher intratumoral SULT2B1b expression had a significantly shorter disease-specific survival (DSS) and disease-free survival (DFS) than those with lower expression. Importantly, increased expression of SULT2B1b significantly predicted poor DSS and DFS and was an independent unfavorable prognostic indicator for stage II patients in both cohorts. Functional studies revealed that overexpression of SULT2B1b promoted CRC cell growth and invasion in vitro. Conversely, knockdown of SULT2B1b inhibited these processes. In conclusion, our findings suggest that SULT2B1b expression correlates with disease progression and metastasis and may serve as a novel prognostic biomarker and potential therapeutic target for patients with CRC.