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p38可预测食管癌患者的抑郁及不良预后。

p38 predicts depression and poor outcome in esophageal cancer.

作者信息

Cheng Yao, Qiao Zhe, Dang Chengxue, Zhou Bin, Li Shaomin, Zhang Wei, Jiang Jiantao, Song Yongchun, Zhang Jin, Diao Dongmei

机构信息

Department of Thoracic Surgery, The Second Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710004, P.R. China.

Department of Surgical Oncology, The First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.

出版信息

Oncol Lett. 2017 Dec;14(6):7241-7249. doi: 10.3892/ol.2017.7129. Epub 2017 Oct 3.

Abstract

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. 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.

摘要

p38丝裂原活化蛋白激酶(MAPK)信号传导与癌症的发生发展有关。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与癌症进展之间的关联,包括对食管癌患者细胞增殖、对沙利度胺的耐药性、吲哚胺2,3-双加氧酶(IDO)表达及预后影响的研究。本回顾性研究纳入了I-III期食管癌患者。共招募了228例食管癌患者,通过免疫组织化学分析肿瘤组织和正常组织中磷酸化(p)-p38和IDO的表达。使用zung自评抑郁量表测量抑郁状态。将p38 cDNA转染到食管癌细胞中,以评估肿瘤细胞活力、对沙利度胺治疗的敏感性和IDO基因表达。采用蛋白质印迹法和流式细胞术分析食管癌细胞中蛋白质表达变化和细胞凋亡情况。p-p38蛋白在68.9%的癌组织中表达,且与患者的抑郁症状、肿瘤复发和不良生存显著相关。实验表明,p-p38的表达可诱导食管癌Eca-109和TE-1细胞活力、对沙利度胺治疗的耐药性以及IDO的表达,且无需应用脂多糖。对患者的进一步随访显示,抑郁也是早期复发和总生存率的独立因素。p38 MAPK表达改变与食管癌患者的不良预后相关。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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fafc/5754885/eeef85787eb3/ol-14-06-7241-g00.jpg

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