P62/Ubiquitin IHC Expression Correlated with Clinicopathologic Parameters and Outcome in Gastrointestinal Carcinomas.

P62/Ubiquitin IHC Expression Correlated with Clinicopathologic Parameters and Outcome in Gastrointestinal Carcinomas.
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DOI:
10.3389/fonc.2015.00070
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发表时间:
2015
影响因子:
4.7
通讯作者:
Cohen C
Cohen C
中科院分区:
医学3区
文献类型:
--
作者:
Mohamed A;Ayman A;Deniece J;Wang T;Kovach C;Siddiqui MT;Cohen C

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P62和泛素是一种小的调节蛋白,被证明与多种恶性肿瘤的预后和生存有关,包括:肝细胞癌、乳腺癌、卵巢癌和一些胃肠道癌。一些试验研究了它们的活性与外在的凋亡途径的联系,并表明它们的自噬修饰在肿瘤发生中具有关键的地位。这些发现解释了它们在控制细胞死亡和存活过程中的重要作用。最近的研究表明,p62和泛素在不同类型的癌症中的过度表达,如三阴性乳腺癌和卵巢癌,与远处转移的发生率直接相关。我们旨在评估p62/泛素在胃肠癌、结肠癌和胰腺癌中的表达,并与注释的临床病理数据相关联。在61例胃癌中,p62核表达阳性率为57%,胞浆表达阳性率为61%;泛素表达阳性率为68.8%,胞浆表达阳性率为29.5%。在45例结肠癌中,p62核表达阳性率为29%,胞浆表达阳性率为71%;泛素表达阳性率为58%,胞浆表达阳性率为44%。在胰腺癌(18例)中,p62核表达阳性率为78%,胞浆表达阳性率为56%;泛素表达阳性率为83%,胞浆表达阳性率为72%。正常胃(6例)、结肠(4例)和胰腺(4例)组织p62和泛素(胞核和胞浆染色20%)均为阴性。泛素高表达与结肠癌(4.14vs1.70,P = 0.04)和胰腺癌(3.07vs0.33,P = 0.03)的淋巴结转移有关。泛素高表达与胰腺癌总生存期相关(1.37vs2.26mos,P = 0.04)。此外,p62高表达患者的低分化程度明显高于低表达患者(21vs17,P = 0.04),但淋巴结转移较少(2.77vs5.73,P = 0.01)。P62和泛素的表达与胃腺癌、结肠癌和胰腺癌的其他临床病理参数无关。结果表明,p62和泛素在胃癌、结肠癌和胰腺癌中均有高表达。研究发现,泛素的高表达对结肠癌和胰腺癌患者的淋巴转移数目有影响,但仅对胰腺癌患者的总体生存率有影响。此外,p62的高表达与胃癌分化程度低、淋巴结转移少有关。
P62 and ubiquitin are small regulatory proteins demonstrated to have implications in the prognosis and survival of various malignancies including: hepatocellular, breast, ovarian, and some gastrointestinal carcinomas. Several trials studied the link of their activity to the extrinsic apoptosis pathway and showed that their autophagy modification has a critical stand point in tumorigenesis. These findings explain their vital role in controlling the process of cell death and survival. It has been shown recently that p62 and ubiquitin overexpression in different types of cancers, such as triple negative breast and ovarian cancers, have directly correlated with incidence of distant metastases. We aim to evaluate p62/ubiquitin expression in gastrointestinal carcinomas of gastric, colonic, and pancreatic origin, and correlate with annotated clinicopathologic data. In gastric carcinoma (61), positive p62 nuclear expression was noted in 57% and cytoplasmic in 61%, while positive ubiquitin was nuclear expressed in 68.8%, and cytoplasmic in 29.5%. In colon carcinoma (45), positive p62 nuclear expression was noted in 29% and cytoplasmic in 71%, while positive ubiquitin was nuclear in 58% and cytoplasmic in 44%. In pancreatic cancer (18), positive p62 nuclear expression was noted in 78% and cytoplasmic in 56%, while positive ubiquitin was nuclear in 83% and cytoplasmic in 72%. Normal gastric (6), colon (4), and pancreatic (4) tissues were negative for both P62 and ubiquitin (nuclear and cytoplasmic staining <20%). Ubiquitin high expression was associated with more lymph node metastases in colon (4.14 vs 1.70, P = 0.04), and pancreatic adenocarcinomas (3.07 vs 0.33, P = 0.03). Also, ubiquitin high expression was associated with worse pancreatic adenocarcinoma overall survival (1.37 vs 2.26 mos, P = 0.04). In addition, gastric cancer patients with high p62 expression tend to have more poorly differentiated grade when compared to those with low expression (21 vs 17, P = 0.04) but less lymph node metastases (2.77 vs 5.73, P = 0.01). P62 and ubiquitin expression did not correlate with other clinicopathologic parameters in gastric, colon or pancreatic denocarcinomas. The results suggest that p62 and ubiquitin are highly expressed in gastric, colonic, and pancreatic carcinomas. High ubiquitin expression was noted to have an impact on number of lymph node metastases in patients with colon and pancreatic adenocarcinomas, but on overall survival only in patients with pancreatic adenocarcinoma. Also, P62 high expression is correlated with poor differentiation, but less lymph node metastases, in gastric carcinoma.
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