Lin Xin, Li Yan, Wang Jin, Han Fei, Lu Shuang, Wang Yu, Luo Wenjian, Zhang Mingqian
Department of Emergency, Yan'an Hospital, Kunming Medical University, Kunming, Yunnan, P.R. China.
Department of Emergency, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.
Oncol Rep. 2017 Sep;38(3):1482-1490. doi: 10.3892/or.2017.5833. Epub 2017 Jul 18.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. We previously identified LHX3 as a new preferentially expressed gene in NSCLC. In the present study, we sought to determine its expression, the clinical relevance and the functional roles in NSCLC. LHX3 expression is sharply increased in carcinoma tissues compared to non-carcinoma tissues. Relational analysis reveals a significant association between LHX3 expression and clinical stage (n=172, p=0.032) or radiotherapy (n=167, p=0.022) of patients. LHX3 expression is much higher in the patients at advanced stages (stage III-IV) than in the patients at early stages (stage I-II, p=0.0304), and LHX3 expression is remarkably increased in the patients with radiotherapy treatment (p=0.0002). Survival analyses indicate that LHX3 is associated with unfavorable survival (n=180, p=0.002) and represents an independent prognostic factor [hazard ratio (HR)=1.834, p=0.004] of the NSCLC patients. Furthermore, LHX3 is associated with unfavorable overall survival (n=866, p=0.004) and represents an independent prognostic factor (HR=2.36, p=0.000) in lung adenocarcinoma (ADC) patients, but is not associated with overall survival of squamous cell carcinoma (SCC) patients (n=524, p=0.27). Further analyses found that LHX3 is an early-stage (n=94, p=0.003) and radiosensitivity (n=45, p=0.002) prognostic factor in ADC patients. The patients without radiotherapy have a significantly prolonged survival compared to those with radiotherapy (p=0.0069). Further functional studies show that forced expression of LHX3 in lung cancer cells obviously promotes cell proliferation and invasion, whereas inhibits cell apoptosis. In summary, LHX3 is an early-stage and radiosensitivity prognostic biomarker, and a novel potential oncogene in ADC.
非小细胞肺癌（NSCLC）是最常见的肺癌类型。我们之前将LHX3鉴定为NSCLC中一种新的优先表达基因。在本研究中，我们试图确定其在NSCLC中的表达、临床相关性及功能作用。与非癌组织相比，癌组织中LHX3表达显著增加。相关性分析显示LHX3表达与患者的临床分期（n = 172，p = 0.032）或放疗情况（n = 167，p = 0.022）之间存在显著关联。LHX3在晚期（III - IV期）患者中的表达远高于早期（I - II期）患者（p = 0.0304），且接受放疗的患者中LHX3表达显著增加（p = 0.0002）。生存分析表明，LHX3与不良生存相关（n = 180，p = 0.002），是NSCLC患者的独立预后因素[风险比（HR）= 1.834，p = 0.004]。此外，LHX3与肺腺癌（ADC）患者的不良总生存相关（n = 866，p = 0.004），是其独立预后因素（HR = 2.36，p = 0.000），但与鳞状细胞癌（SCC）患者的总生存无关（n = 524，p = 0.27）。进一步分析发现，LHX3是ADC患者的早期（n = 94，p = 0.003）和放射敏感性（n = 45，p = 0.002）预后因素。未接受放疗的患者与接受放疗的患者相比，生存期显著延长（p = 0.0069）。进一步的功能研究表明，肺癌细胞中LHX3的强制表达明显促进细胞增殖和侵袭，而抑制细胞凋亡。总之，LHX3是ADC的早期和放射敏感性预后生物标志物，也是一种新的潜在癌基因。
