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Phosphoserine Aminotransgerase I Is A predictor of Early Recurrence and Poor Prognosis of Resected Stage I Non‐small Cell Lung Cancer That Induces Metastasis via MMP1 Activation
Author(s) -
Chan YungChieh,
Liu YuPeng,
Su ChiaYi,
Jan YihHua,
Yang YiFang,
Chang YuChan,
Lai ChuChing,
Hsaio Michael
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.58.5
Subject(s) - tissue microarray , mmp1 , lung cancer , stage (stratigraphy) , gene knockdown , immunohistochemistry , medicine , cancer research , adenocarcinoma , metastasis , oncology , cancer , pathology , biology , cell culture , gene expression , gene , paleontology , biochemistry , genetics
Stage I non‐small cell lung cancer (NSCLC) is potentially curable after completely resection. However, recurrence may occur in 30 % of the stage I cases and influence prognosis. It is important to identify biomarkers that can predict the early recurrence in Stage I lung cancer patients. By using publicly available microarray database, we have identified Phosphoserine Aminotransferase I (PSAT1) which overexpression is associated with poor prognosis ( P <0.001) with hazard ratio of 2.09 ( P =0.00048) in stage I and II of lung cancer patients. The immunohistochemical staining was carried out with 104 specimens of NSCLC, which showed higher PSAT1 expression level in tumor tissue than adjacent non‐tumor tissue ( P <0.011). High PSAT1 immunoreactivity was relevant to shorter disease free survival ( P =0.034) in early stage adenocarcinoma. Two way complementary overexpression and knockdown of PSAT1 in low invasive and high invasive lung cancer cell promotes invasion and migration, respectively. Furthermore, high‐throughput promoter screening showed significant activation of MMP1 promoter (10‐fold, P<0.01) by PSAT1 expression. MMP1 knockdown in PSAT1 overexpressed cells inhibited invasion, suggested that MMP1 is a downstream target of PSAT1 in lung cancer cells. In summary, our results indicate that PSAT1 is a novel predictor in stage I NSCLC, which promote cell invasion through the activation of MMP1 pathway.