The clinicopathological and prognostic implications of tyrosine phosphatase SHP2 and ankyrin Hook1 gene expression in non- small cell lung cancer patients treated with gemcitabine plus platinum as first-line chemotherapy

酪氨酸磷酸酶 SHP2 和锚蛋白 Hook1 基因表达对接受吉西他滨联合铂类一线化疗的非小细胞肺癌患者的临床病理学和预后意义

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作者:Hongyu Yang, Lingjuan He, Yi Zhang, Yinyan Li, Xin Huang, Ying Li, Yan Lou, Linrun Wang

Background

SHP2, a widely expressed phosphatase, which has been linked to the initiation, progression and prognosis of various malignancies. We previously identified a new SHP2 anchorage protein Hook1 in the alveolar II epithelial cells, and it is suggested that Hook1 is a novel endogenous suppressor molecule of SHP2 phosphatase activity. Nevertheless, few studies have been mentioned the clinicopathological and prognostic relevance of SHP2 and Hook1 expression in patients with non-small cell lung cancer (NSCLC).

Conclusions

The present study suggested that NSCLC patients with negative SHP2 expression could benefit from gemcitabine plus carboplatin chemotherapy, and further study is needed to confirm the prognostic value of SHP2 and Hook1.

Methods

A total of 61 patients with NSCLC receiving gemcitabine plus carboplatin chemotherapy were studied. Immunohistochemical staining was conducted to determine the protein expression of SHP2 and Hook1. The relationships between gene expression and clinical and pathological factors, as well as prognosis, were evaluated.

Results

A significant correlation was observed between the SHP2 and Hook1 expression, with a total expression rate of 71.4%. The positive expression of Hook1 in adenocarcinoma and in stage IIIb-IV was higher than that in patients with squamous (73.5% vs. 31.2%, P=0.013) and I-IIIa (75% vs. 48.8%, P=0.05), suggesting that Hook1 might act as an indicator of NSCLC status. However, no significant correlation was observed between Hook1 expression and survival time (P>0.05). In contrast, patients with negative SHP2 expression had a higher survival rate (median overall survival 68 vs. 24 months, P=0.003). Cox multivariate regression analysis showed that SHP2 was an independent indicator for overall survival (P=0.009). Conclusions: The present study suggested that NSCLC patients with negative SHP2 expression could benefit from gemcitabine plus carboplatin chemotherapy, and further study is needed to confirm the prognostic value of SHP2 and Hook1.

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