p38 predicts depression and poor outcome in esophageal cancer.

p38 predicts depression and poor outcome in esophageal cancer.
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p38 预测食管癌的抑郁症和不良预后

DOI:
10.3892/ol.2017.7129
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发表时间:
2017-12
期刊:
影响因子:
2.9
通讯作者:
Diao D
Diao D
中科院分区:
医学4区
文献类型:
--
作者:
Cheng Y;Qiao Z;Dang C;Zhou B;Li S;Zhang W;Jiang J;Song Y;Zhang J;Diao D

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p38丝裂原活化蛋白激酶(MAPK)信号通路与癌症的发生和发展有关。然而,这种关联的确切机制尚不清楚。本研究的目的是评估p38与食管癌进展之间的关系,包括研究p38对食管癌患者细胞增殖、对沙利度胺、吲哚胺2,3-双加氧酶(IDO)表达和预后的影响。本回顾性研究纳入了I-III期食管癌患者。选取228例食管癌患者,采用免疫组化方法分析肿瘤组织和正常组织中磷酸化(p)-p38和IDO的表达情况。采用Zung抑郁自评量表测量抑郁状态。将P38 cDNA转染食管癌细胞,观察肿瘤细胞活力、对沙利度胺的敏感性及IDO基因表达。Western blotting和流式细胞术检测食管癌细胞蛋白表达变化及凋亡情况。P-p38蛋白在68.9%的癌组织中表达,与患者的抑郁症状、肿瘤复发及不良生存率显著相关。体外实验表明,p-p38的表达可诱导食管癌Eca-109和TE-1细胞的活力、对沙利度胺的耐药性,以及在不应用脂多糖的情况下IDO的表达。进一步随访发现,抑郁症也是早期复发和总生存率的独立因素。食管癌患者p38 MAPK表达改变与预后不良相关。P38可能是预测食管癌患者抑郁症状和预后的潜在生物标志物。
p38 mitogen-activated protein kinase (MAPK) signaling has been implicated in the cancer development and progression. However, the precise mechanism of this association remains unknown. The aim of the present study was to evaluate the association between p38 and cancer progression, including investigations into the effects on cell proliferation, resistance to thalidomide, indoleamine 2,3-dioxygenase (IDO) expression and prognosis in patients with esophageal cancer. The present retrospective study included patients with stage I–III esophageal cancer. A total of 228 patients with esophageal cancer were recruited to analyze the expression of phosphorylated (p)-p38 and IDO in tumor, and normal tissues through immunohistochemistry. Depression status was measured using the Zung Self-Rating Depression Scale. P38 cDNA was transfected into esophageal cancer cells to assess tumor cell viability, sensitivity to thalidomide treatment and IDO gene expression. Western blotting and flow cytometry was used to analyze protein expression alterations, and apoptosis in esophageal cancer cells. P-p38 protein was expressed in 68.9% of cancer tissues, and was significantly associated with depressive symptoms, tumor recurrence and poor survival of patients. In vitro experiments revealed that the expression of p-p38 induced esophageal cancer Eca-109 and TE-1 cell viability, and resistance to thalidomide treatment, as well as in the expression of IDO without the application of lipopolysaccharides. Further follow-up of patients revealed that depression was also an independent factor for early recurrence and overall survival rate. Altered p38 MAPK expression was associated with poor outcome in patients with esophageal cancer. p38 may be a potential biomarker for the prediction of depressive symptoms and prognosis in patients with esophageal cancer.
DOI: 10.1186/1471-2407-9-190
发表时间: 2009-06-17
期刊: BMC cancer
影响因子: 3.8
作者:
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