Prognostic Impact of a Novel Tumor Marker and Inflammation Index for Patients With Non-small-cell Lung Cancer.
- 作者列表："Tomita M","Maeda R","Ayabe T","Nakamura K
BACKGROUND/AIM:Different tumor markers and systemic inflammation have been linked with cancer development and poor outcome. We aimed to establish a novel non-invasive prognostic index for patients with resectable non-small cell lung cancer (NSCLC) based on serum carcinoembryonic antigen (CEA) and C-reactive protein (CRP). PATIENTS AND METHODS:Four hundred and sixty-two patients curatively resected for NSCLC between 2008 and 2014 were included. All patients with a follow-up period of less than 5 years were omitted. The geometric mean of the normalized serum CEA and CRP levels was used as a novel tumor marker and inflammation index (TMII). The cut-off value of TMII was determined by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate analyses were used to identify the relative risk factors for survival. RESULTS:ROC curve analysis revealed a TMII cut-off value of 0.46. The group with high TMII displayed more adverse clinical characteristics. Furthermore, compared to patients with low TMII, the group with high TMII had significantly poorer survival. On multivariate analysis, TMII was independently associated with survival. CONCLUSION:We established a novel prognostic index (TMII) based on serum CEA and CRP. Preoperative TMII may predict poor outcomes in patients with NSCLC.
背景/目的: 不同的肿瘤标志物和全身性炎症与癌症的发展和不良预后有关。我们旨在建立一种基于血清癌胚抗原 (CEA) 的非小细胞肺癌 (NSCLC) 患者无创性预后指标。和C反应蛋白 (CRP)。 患者和方法: 纳入了 2008 年至 2014 年间的例经手术切除的非小细胞肺癌患者。所有随访时间小于 5 年的患者均被省略。标准化血清CEA和CRP水平的几何平均值被用作新的肿瘤标志物和炎症指数 (TMII)。通过受试者工作特征 (ROC) 曲线分析确定TMII的截止值。采用单因素和多因素分析确定生存的相关危险因素。 结果: ROC曲线分析显示TMII临界值为 0.46。高TMII组表现出更多的不良临床特征。此外，与具有低TMII的患者相比，具有高TMII的组具有显著更差的存活率。在多变量分析中，TMII与生存率独立相关。 结论: 我们建立了一个基于血清CEA和CRP的新的预后指标 (TMII)。术前TMII可预测NSCLC患者的不良结局。
METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.
METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.
METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.