The expression patterns and the diagnostic/prognostic roles of PTPN family members in digestive tract cancers
The expression patterns and the diagnostic/prognostic roles of PTPN family members in digestive tract cancers
复制标题
PTPN家族成员在消化道癌症中的表达模式及其诊断/预后作用
DOI：
10.1186/s12935-020-01315-7
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发表时间：
2020-06-12
影响因子：
5.8
通讯作者：
Jing, Jing-Jing
中科院分区：
文献类型：
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作者：
Chen, Jing;Zhao, Xu;Jing, Jing-Jing
背景非受体蛋白酪氨酸磷酸酶(PTPN)是一组参与酪氨酸磷酸化的酶。本研究旨在阐明PTPN家族成员的表达模式与消化道癌的诊断及预后的关系。方法用Oncomine和Ualcan分析PTPN的表达。通过UCSC Xena下载来自癌症基因组图谱(TCGA)的数据进行验证，以探讨PTPN表达与消化道癌的诊断、临床病理参数和生存期的关系。利用David数据库进行基因本体论丰富分析。利用GeneMANIA构建基因-基因相互作用网络，利用串口与Cytoscape耦合构建蛋白质-蛋白质相互作用网络。应用CCLE技术检测肿瘤细胞系中差异表达的PTPN的表达。此外，通过组织学验证，进一步分析了4种PTPN在消化道癌中的表达。结果根据Oncomine、Ualcan和TCGA资料，PTPN家族成员大多与消化道肿瘤有关。几个PTPN成员在消化道癌中有差异表达。对于食道癌，PTPN1和PTPN12水平与发病率相关，PTPN20与预后不良相关。在胃腺癌(STAD)中，PTPN2和PTPN12的表达与肿瘤的发生有关，PTPN3、PTPN5、PTPN7、PTPN11、PTPN13、PTPN14、PTPN18和PTPN23的表达与病理分级有关，PTPN20的表达与TNM分期和N分期有关，PTPN22的表达与T分期和病理分级有关，PTPN5和PTPN13的低表达提示STAD的总体生存较差，PTPN6的高表达提示预后较好。PTPN5、PTPN12、PTPN14的表达与结直肠癌的TNM分期、N分期相关，PTPN5、PTPN7的高表达与死亡危险性增加相关。CCLE分析表明，在食道癌细胞系中，PTPN1、PTPN4和PTPN12高表达；在胃癌细胞系中，PTPN2和PTPN12高表达；在结直肠癌细胞系中，PTPN12高表达，而PTPN22表达下调。组织学验证实验结果显示PTPN22在结直肠癌中的表达存在差异，而PTPN12在胃癌和结直肠癌中的表达存在差异。结论PTPN家族成员在消化道肿瘤中有不同程度的表达。PTPN基因与患者的临床病理参数相关。PTPN12在STAD和CRC中的表达均上调，可作为诊断的生物标志物。在我们的组织学验证实验中，PTPN12在胃癌和结直肠癌中的差异表达以及PTPN22在结直肠癌中的表达。
Background Non-receptor protein tyrosine phosphatases (PTPNs) are a set of enzymes involved in the tyrosyl phosphorylation. The present study intended to clarify the associations between the expression patterns of PTPN family members, and diagnosis as well as the prognosis of digestive tract cancers. Methods Oncomine and Ualcan were used to analyze PTPN expressions. Data from The Cancer Genome Atlas (TCGA) were downloaded through UCSC Xena for validation and to explore the relationship of the PTPN expression with diagnosis, clinicopathological parameters and survival of digestive tract cancers. Gene ontology enrichment analysis was conducted using the DAVID database. The gene-gene interaction network was performed by GeneMANIA and the protein-protein interaction (PPI) network was built using STRING portal coupled with Cytoscape. The expression of differentially expressed PTPNs in cancer cell lines were explored using CCLE. Moreover, by histological verification, the expression of four PTPNs in digestive tract cancers were further analyzed. Results Most PTPN family members were associated with digestive tract cancers according to Oncomine, Ualcan and TCGA data. Several PTPN members were differentially expressed in digestive tract cancers. For esophageal carcinoma (ESCA), PTPN1 and PTPN12 levels were correlated with incidence; PTPN20 was associated with poor prognosis. For stomach adenocarcinoma (STAD), PTPN2 and PTPN12 levels were correlated with incidence; PTPN3, PTPN5, PTPN7, PTPN11, PTPN13, PTPN14, PTPN18 and PTPN23 were correlated with pathological grade; PTPN20 expression was related with both TNM stage and N stage; PTPN22 was associated with T stage and pathological grade; decreased expression of PTPN5 and PTPN13 implied worse overall survival of STAD, while elevated PTPN6 expression indicated better prognosis. For colorectal cancer (CRC), PTPN2, PTPN21 and PTPN22 levels were correlated with incidence; expression of PTPN5, PTPN12, and PTPN14 was correlated with TNM stage and N stage; high PTPN5 or PTPN7 expression was associated with increased hazards of death. CCLE analyses showed that in esophagus cancer cell lines, PTPN1, PTPN4 and PTPN12 were highly expressed; in gastric cancer cell lines, PTPN2 and PTPN12 were highly expressed; in colorectal cancer cell lines, PTPN12 was highly expressed while PTPN22 was downregulated. Results of histological verification experiment showed differential expressions of PTPN22 in CRC, and PTPN12 in GC and CRC. Conclusions Members of PTPN family were differentially expressed in digestive tract cancers. Correlations were found between PTPN genes and clinicopathological parameters of patients. Expression of PTPN12 was upregulated in both STAD and CRC, and thus could be used as a diagnostic biomarker. Differential expression of PTPN12 in GC and CRC, and PTPN22 in CRC were presented in our histological verification experiment.