Silencing of XB130 is associated with both the prognosis and chemosensitivity of gastric cancer.

Silencing of XB130 is associated with both the prognosis and chemosensitivity of gastric cancer.
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DOI:
10.1371/journal.pone.0041660
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Liao W
Liao W
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shi M;Huang W;Lin L;Zheng D;Zuo Q;Wang L;Wang N;Wu Y;Liao Y;Liao W

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XB 130是一种新发现的衔接蛋白,据报道其可促进甲状腺肿瘤的生长,但其在其他类型癌症如胃癌(GC)的进展中的作用尚不清楚。因此,我们研究了XB 130表达与胃癌患者预后之间的关系。研究对象为411例I期至IV期胃癌患者。检测胃癌手术标本中XB 130的表达。Kaplan-Meier分析和考克斯比例风险模型用于评估XB 130对生存和复发的预后意义。建立稳定转染XB 130短发夹状RNA的胃癌细胞系,分析XB 130对胃癌化疗敏感性的影响。结果显示,正常胃组织中有XB 130 mRNA和蛋白表达。当XB 130免疫组化染色低时,IV期患者的总生存时间和I-III期患者根治性切除术后的无病期显著短于当XB 130免疫组化染色高时(均p<0.05)。XB 130表达还预测了肿瘤对几种化疗药物的敏感性。5-氟尿嘧啶(5-FU)、顺铂和伊立替康以剂量依赖性方式抑制XB 130沉默的SGC 7901细胞和野生型细胞的活力,但顺铂和伊立替康对sXB 130沉默的GC细胞更敏感,5-FU对野生型细胞显示出更高的敏感性。当用5-FU治疗时,XB 130高表达肿瘤患者的生存率高于低表达肿瘤患者。这些发现表明,降低XB 130蛋白表达是胃癌患者生存期缩短和复发率升高以及对化疗反应的预后生物标志物。
XB130 is a newly characterized adaptor protein that was reported to promote thyroid tumor growth, but its role in the progression of other kinds of cancer such as gastric cancer (GC) remains unknown. Accordingly, we investigated the association between XB130 expression and the prognosis of GC patients. The subjects were 411 patients with GC in stages I to IV. XB130 expression was examined in surgical specimens of GC. Kaplan-Meier analysis and the Cox proportional hazards model were used to assess the prognostic significance of XB130 for survival and recurrence. Moreover, GC cells stably transfected with XB130 short hairpin RNA were established to analyze the effect of XB130 on sensitivity of chemotherapy. The results show that both XB130 mRNA and protein expression were detectable in normal gastric tissues. The overall survival time of stage IV patients and the disease-free period after radical resection of GC in stage I–III patients were significantly shorter when immunohistochemical staining for XB130 was low than when staining was high (both p<0.05). XB130 expression also predicted tumor sensitivity to several chemotherapy agents. Viability of both XB130-silenced SGC7901 cells and wild-type cells was suppressed by 5-fluorouracil (5-FU), cisplatin, and irinotecan in a dose-dependent way, but cisplatin and irinotecan were more sensitive against sXB130-silenced GC cells and 5-FU showed higher sensitivity to wild-type cells. When treated by 5-FU, patients with high expression of XB130 tumors had a higher survival rate than those with low expression tumors. These findings indicate that reduced XB130 protein expression is a prognostic biomarker for shorter survival and a higher recurrence rate in patients with GC, as well as for the response to chemotherapy.
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