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Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma.
Scientific Reports ( IF 3.8 ) Pub Date : 2019-12-24 , DOI: 10.1038/s41598-019-56059-w Lenka Cervenkova 1, 2 , Ondrej Vycital 1, 3 , Jan Bruha 1, 3 , Jachym Rosendorf 1, 3 , Richard Palek 1, 3 , Vaclav Liska 1, 3 , Ondrej Daum 1, 4 , Beatrice Mohelnikova-Duchonova 5 , Pavel Soucek 1
Scientific Reports ( IF 3.8 ) Pub Date : 2019-12-24 , DOI: 10.1038/s41598-019-56059-w Lenka Cervenkova 1, 2 , Ondrej Vycital 1, 3 , Jan Bruha 1, 3 , Jachym Rosendorf 1, 3 , Richard Palek 1, 3 , Vaclav Liska 1, 3 , Ondrej Daum 1, 4 , Beatrice Mohelnikova-Duchonova 5 , Pavel Soucek 1
Affiliation
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ATP-binding cassette (ABC) and solute carrier (SLC) transporters translocate diverse substances across cellular membranes and their deregulation may cause drug resistance of cancers. This study investigated significance of protein expression and cellular localization of the previously suggested putative prognostic markers ABCC2 and SLC22A3 in pancreatic cancer patients. Protein localization and brush border staining intensity of ABCC2 and SLC22A3 was assessed in tumor tissue blocks of 65 pancreatic cancer patients and associated with clinical data and survival of patients with regard to therapy. Negative SLC22A3 brush border staining in pancreatic tumors significantly increased the risk of both disease progression and patient´s death in univariate analyses. Multivariate analyses confirmed the association of SLC22A3 expression with progression-free survival of patients. A subgroup analysis of patients treated with regimens based on nucleoside analogs suggested that patients with negative brush border staining or apical localization of SLC22A3 in tumor cells have worse overall survival. The combination of positive ABCC2 and negative SLC22A3 brush border staining predicted worst overall survival and patients with positive brush border staining of both proteins had best overall and progression-free survival. The present study shows for the first time that the protein presence and to some extent also localization of SLC22A3 significantly associate with prognosis of pancreatic cancer in both unstratified and chemotherapy-treated patients. The combination of ABCC2 and SLC22A3 brush border staining also needs further attention in this regard.
中文翻译：
ABCC2和SLC22A3的蛋白表达与胰腺腺癌的预后相关。
ATP结合盒（ABC）和溶质载体（SLC）转运蛋白使各种物质跨细胞膜转运，它们的失调可能导致癌症的耐药性。这项研究调查了胰腺癌患者中先前提出的假定的预后标志物ABCC2和SLC22A3的蛋白表达和细胞定位的意义。在65例胰腺癌患者的肿瘤组织块中评估了ABCC2和SLC22A3的蛋白质定位和刷状边界染色强度，并与临床数据和患者生存率相关联。在单因素分析中，胰腺肿瘤中SLC22A3刷状边界阴性显示显着增加了疾病进展和患者死亡的风险。多变量分析证实了SLC22A3表达与患者无进展生存相关。对基于核苷类似物的治疗方案的患者进行的亚组分析表明，在肿瘤细胞中刷状边界染色阴性或SLC22A3根尖定位的患者的总生存期较差。阳性ABCC2和阴性SLC22A3刷状边界染色的组合预示了最差的总体存活率，并且两种蛋白的刷状边界染色呈阳性的患者的总体和无进展生存期均最佳。本研究首次表明，在未分层和化疗后的患者中，SLC22A3的蛋白存在以及在某种程度上还与胰腺癌的预后显着相关。
更新日期：2019-12-25
中文翻译：
ABCC2和SLC22A3的蛋白表达与胰腺腺癌的预后相关。
ATP结合盒（ABC）和溶质载体（SLC）转运蛋白使各种物质跨细胞膜转运，它们的失调可能导致癌症的耐药性。这项研究调查了胰腺癌患者中先前提出的假定的预后标志物ABCC2和SLC22A3的蛋白表达和细胞定位的意义。在65例胰腺癌患者的肿瘤组织块中评估了ABCC2和SLC22A3的蛋白质定位和刷状边界染色强度，并与临床数据和患者生存率相关联。在单因素分析中，胰腺肿瘤中SLC22A3刷状边界阴性显示显着增加了疾病进展和患者死亡的风险。多变量分析证实了SLC22A3表达与患者无进展生存相关。对基于核苷类似物的治疗方案的患者进行的亚组分析表明，在肿瘤细胞中刷状边界染色阴性或SLC22A3根尖定位的患者的总生存期较差。阳性ABCC2和阴性SLC22A3刷状边界染色的组合预示了最差的总体存活率，并且两种蛋白的刷状边界染色呈阳性的患者的总体和无进展生存期均最佳。本研究首次表明，在未分层和化疗后的患者中，SLC22A3的蛋白存在以及在某种程度上还与胰腺癌的预后显着相关。
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