Multiple Pulmonary and Pleural Metastases in Recurrent Intracranial Meningioma with Genetic Changes: Case Report and Review of the Literature.
- 作者列表："He N","Zhong L","Lei K
BACKGROUND:According to the 2016 World Health Organization classification of central nervous system tumors, meningiomas are classified into 3 grades: I, II, and III. It has been reported that 2%-10% of meningiomas exhibit aggressive behavior, and 0.1%-1% of all patients with primary meningiomas develop distant metastases. Past studies have shown that genomic instability is strongly correlated with the risk of meningioma recurrence. Because of the rarity of this tumor, few papers have reported the prognosis and treatment of anaplastic meningioma. Under these circumstances, we present a case of multiple pulmonary and pleural metastases from a recurrent intracranial meningioma with some genetic changes. CASE DESCRIPTION:In the case, a previously healthy man aged 39 years was diagnosed with anaplastic meningioma. Postoperatively, due to multiple pulmonary and pleural metastases, adjuvant radiation, chemotherapy, and Gamma knife radiosurgery was subsequently performed. Molecular genetic examination with chromosomal microarray analysis showed that there were chromosomal abnormalities, including amplification in 1q and chr12; loss in 1p, 9p, and 22q; and catastrophe in chr8 and chr17 in both the previous brain meningioma and lung tissues, confirming the diagnosis of pulmonary metastasis of the initial grade III meningioma. CONCLUSIONS:The molecular characterization of meningiomas has identified genetic biomarkers that influence tumor characteristics, such as tumor behavior, malignancy, and location. The combined analyses of genetic and epigenetic changes in meningiomas may allow researchers to unveil a more comprehensive understanding of tumor progression mechanisms.
背景: 根据世界卫生组织 2016 中枢神经系统肿瘤分类，脑膜瘤分为 ⅰ 、 ⅱ 、 ⅲ 级。据报道，2%-10% 的脑膜瘤表现出侵袭性行为，并且 0.1%-1% 的原发性脑膜瘤患者发生远处转移。过去的研究表明，基因组不稳定性与脑膜瘤复发风险密切相关。由于这种肿瘤的罕见性，很少有文献报道间变性脑膜瘤的预后和治疗。在这些情况下，我们提出了一个病例的多发性肺和胸膜转移的复发性颅内脑膜瘤与一些基因的变化。 病例描述: 在该病例中，一名既往健康的 39 岁男性被诊断患有间变性脑膜瘤。术后，由于多发肺和胸膜转移，随后进行了辅助放疗，化疗和伽玛刀放射外科手术。染色体微阵列分析分子遗传学检查显示染色体异常，包括 1q和chr12 扩增; 1p、 9p和 22q缺失; 和chr8 和chr17 在以前的脑脑膜瘤和肺组织中的突变，证实了最初的III级脑膜瘤的肺转移的诊断。 结论: 脑膜瘤的分子特征已经确定了影响肿瘤特征的遗传生物标志物，如肿瘤行为，恶性和位置。脑膜瘤的遗传和表观遗传变化的组合分析可能使研究人员揭示更全面的肿瘤进展机制。
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.