| Summary: | 碩士 === 國立臺灣大學 === 醫學檢驗暨生物技術學研究所 === 97 === Background: JAG-1 is a ligand of Notch signaling pathway and can regulate cell differentiation and proliferation in several cancers. Recent study indicated that JAG1 is a gene associated with tumor invasion. Therefore, we investigated the clinical significance of JAG1 expression in non–small-cell lung cancer (NSCLC) patients and its role in lung cancer progression.
Methods: We induced JAG1 overexpression or knockdown in human lung cancer cell lines (CL1-0, CL1-5, A549 and NCI-H226) and analyzed cell anchorage-independent growth, proliferation, cell migration, invasion, and in vivo metastasis, as well as matrix metalloproteinase-2 (MMP-2) and MMP-9 activities. The potential downstream genes of JAG1 were identified by oligonucleotide microarray and were validated by quantitative reverse transcription–polymerase chain reaction (RT-PCR). We measured JAG1 expression in tumors and adjacent normal tissues of 90 NSCLC patients by RT-PCR. Correlation of JAG1 expression and overall survival was determined using the log-rank test and multivariable Cox proportional hazards regression analysis. All statistical tests were two-sided.
Results: JAG1 enhances anchorage-independent growth, cell migration, invasion, and in vivo metastasis through upregulating the expression of heat shock 70kDa protein 2 (HSPA2) that is independent of Notch pathway. JAG1 expression was higher in tumors than in adjacent normal tissue in 14 of 20 patients of subtype squamous carcinoma of NSCLC patients studied (P=0.017). Subtype squamous carcinoma of NSCLC patients with high JAG1 expressing tumors had shorter overall survival (HR = 2.87; 95% CI = 0.99 to 8.33; P = 0.04) than those with low-expressing JAG1. However, in clinical analysis, JAG1 expression was not associated with overall survival in either NSCLC or subtype adenocarcinoma of NSCLC patients.
Conclusion: JAG1 showed an oncogenic characteristic in Subtype squamous carcinoma of NSCLC, and high JAG1 expression is associated with reduced survival of subtype squamous cell carcinoma patients.
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