Prognostic value of distant metastatic sites in stage IV endometrial cancer: A SEER database study of 2948 women.
IV期子宫内膜癌远处转移部位的预后价值: 2948 名女性的SEER数据库研究。
- 作者列表："Liu Y","Chi S","Zhou X","Zhao R","Xiao C","Wang H
OBJECTIVE:To evaluate the prognosis of women with distant metastasis at the time of endometrial cancer (EC) diagnosis and identify prognostic factors according to metastatic site. METHODS:A retrospective cohort study of women diagnosed with EC according to the SEER database between 2010 and 2014. Univariate and multivariate Cox regression was used to identify variables associated with overall survival. Kaplan-Meier curves were used to compare survival among different groups. RESULTS:Overall, 2948 women with stage IV EC were identified. The most common distant metastatic site was the lung. Having a distant metastatic site independently predicted overall survival. Using brain metastasis as a reference, overall survival was longer for liver (P=0.049), lung (P=0.005), and bone (P=0.019) metastasis. Relative to no distant metastasis, overall survival was shorter for women with one (P<0.001) or two or more (P<0.001) sites of distant metastasis. Overall survival was independently influenced by tumor grade, insurance status, and surgery among women with only lung metastasis. CONCLUSION:The findings showed that the prognosis of women with stage IV EC differs by distant metastatic site, and identified several predictors of poor survival. They may help clinicians to better predict prognosis for newly diagnosed cases of EC with distant metastasis.
目的: 评估子宫内膜癌诊断时远处转移患者的预后，并根据转移部位确定预后因素。 方法: 根据SEER数据库，对 2010 年至 2014 年间诊断为EC的女性进行回顾性队列研究。使用单变量和多变量Cox回归来确定与总生存期相关的变量。Kaplan-Meier曲线用于比较不同组之间的存活率。 结果: 总共确定了 2948 名患有IV期EC的女性。最常见的远处转移部位是肺。具有远处转移部位独立预测总生存期。以脑转移为参照，肝 (P = 0.049) 、肺 (P = 0.005) 和骨 (P = 0.019) 转移的总生存期更长。相对于无远处转移，具有 1 个 (P<0.001) 或 2 个或更多 (P<0.001) 远处转移部位的女性的总生存期较短。在仅有肺转移的女性中，肿瘤分级、保险状态和手术独立影响总生存期. 结论: 研究结果表明，IV期女性EC的预后因远处转移部位而异，并确定了几个生存不良的预测因子。它们可能有助于临床医生更好地预测新诊断的EC伴远处转移病例的预后。
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.