Association of nuclear localization of SHP2 and YAP1 with unfavorable prognosis in non-small cell lung cancer

doi:doi.org/10.1016/j.prp.2019.01.027

中山醫學大學機構典藏 CSMUIR > 醫學院 > 醫學系 > 期刊論文 > Item 310902500/21675

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/21675

Title:	Association of nuclear localization of SHP2 and YAP1 with unfavorable prognosis in non-small cell lung cancer
Authors:	Ming-Jenn Chen;Yao-Chen Wang;De-Wei Wu;Chi-Yi Chen;Huei Lee
Keywords:	SHP2;Prognosis;NSCLC
Date:	2019-04
Issue Date:	2021-08-23T01:52:34Z (UTC)
Publisher:	Elsevier Inc.
Abstract:	Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2) is ubiquitously expressed in cytoplasmic localization, which in turn confers tumor malignancy and poor prognosis in various human cancers. YAP1 interacts with SHP2 to promote translocation of SHP2 to nucleus, which consequently promotes Wnt target activation. However, the oncogenic role of the nuclear localization of SHP2 in human cancers remains unclear. We hypothesized that nuclear SHP2 localization, in combination with nuclear YAP1 expression, could be associated with poor overall survival (OS) and relapse free survival (RFS) due to an increase in cyclin D1 and c-Myc mRNA expression following activation of Wnt/ß-catenin signaling. Immunohistochemical analysis of SHP2 and YAP1 protein expression in 102 tumors resected from patients with NSCLC revealed that nuclear SHP2 expression was well correlated with nuclear YAP1 expression (P < 0.001). Evaluation of cyclin D1 and c-Myc mRNA levels by the real-time reverse-phase polymerase chain reaction (RT-PCR) revealed that patients with high cyclin D1 and high c-Myc mRNA expressing tumors more commonly showed high nuclear YAP1 and high nuclear SHP2 (high/high) rather than the high/low, low/high, or low/low combinations (P < 0.001 for cyclin D1 and c-Myc). Kaplan-Meier and Cox-regression models showed OS and RFS to be poorer in patients in the high/high subgroup than in the low/low subgroup (OS: HR = 2.85, 95% CI, 1.52–5.35, P = 0.001; RFS: HR = 2.55, 95% CI, 1.37–4.72, P = 0.003). No prognostic significance was observed for the other two subgroups (low/high and high/low) when compared to the low/low subgroup in this study population. Therefore, we suggest that the prognostic value of SHP2 could reflect the nuclear localization of SHP2 and its interaction with nuclear YAP1, which led to subsequent upregulation of cyclin D1 and c-Myc mRNA expression via activation of the Wnt/ß-catenin signaling pathway.
URI:	https://ir.csmu.edu.tw:8080/handle/310902500/21675
Relation:	Pathology - Research and Practice Volume 215, Issue 4, April 2019, Pages 801-806
Appears in Collections:	[醫學系] 期刊論文

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