Correlation of exosomal microRNA clusters with bone metastasis in non-small cell lung cancer.

20-40% of lung cancer patients develop bone metastasis (BM) with significantly decreased overall survival. Currently, BM is mainly diagnosed by computerized tomography (CT) scan or magnetic resonance imaging (MRI) when symptom develops. Novel biomarkers with higher prediction value of BM are needed. Plasma-derived exosomal microRNAs had been isolated and sequenced of total 30 non-small cell lung cancer (NSCLC) patients including 16 with bone metastasis and 14 without bone metastasis. Hierarchical clustering based on the total miRNA profile can clearly separate cancer patients and healthy individuals (H), but not patients with (BM +) or without (BM-) BM. Weight Co-expression network of miRNAs (WGCNA) analyses identified three consensus clusters (A, B, C) of highly correlated miRNAs, among which cluster B (144 miRNAs) showed significantly differential expression in lung cancer patients, especially in BM + group. Pathway analysis of cluster B miRNAs revealed enrichment in metabolic pathways that may involve in preconditioning of the metastatic niche. Three differentially expressed miRNAs between BM + and BM- patients within cluster B were identified as miR-574-5p, a suppressor of Wnt/ß-catenin pathway, was down-regulated, while miR-328-3p and miR-423-3p, two activators of the same pathway, were up-regulated in BM + patients. Cluster A miRNAs (n = 49) also showed trend of upregulation in BM + patients. Interestingly, pathway analysis indicated that 43 of them are associated with chromosome14, which has been suggested to promote epithelial-mesenchymal transition (EMT) and bone metastasis.

Immunoglobulin G4-related hypertrophic pachymeningitis with spinal cord compression: A case report.

IgG4-related disease (IgG4-RD) is a recently recognized inflammatory condition that can be found in many organs. However, spinal involvement is rare and has been described only in case reports and series. Here, we report a rare case of spinal IgG4-RD that resulted in hypertrophic pachymeningitis with spinal cord compression. This case expands the phenotypic presentation for the neurological sequelae of IgG4-RD. Our case hints that spinal IgG4-RD may be misdiagnosed, and IgG4-RD in patients should be considered when the patient has a dural mass. Although early surgery, steroids, and/or immunosuppressive therapy may prevent neurological complications, the side effects should receive more attention during treatment.

Correlation of plasma exosomal microRNAs with the efficacy of immunotherapy in EGFR/ALK wild-type advanced non-small cell lung cancer.

BACKGROUND: Immunotherapy has become an important treatment option for patients with advanced non-small cell lung cancer (NSCLC). At present, none of these existing biomarkers can effectively stratify true responders and there is an urgent need for identifying novel biomarkers. Exosomes derived from the serum of patients with cancer have been proven to be reliable markers for cancer diagnosis. Here, we explored the possibility of using plasma-derived exosomal microRNAs as potential biomarkers for optimal selection of patients with advanced EGFR/ALK negative NSCLC to immunotherapy. METHODS: From June 2017 to February 2019, 30 patients with advanced EGFR/ALK wild-type (WT) NSCLC who received PD-1/PD-L1 inhibitors were enrolled. The efficacy evaluation was conducted after every three cycles of treatment according to RECIST 1.1. Plasma samples of these patients were collected before the administration of PD-1/PD-L1 inhibitors as baseline, and after every three cycles if the patients achieved partial response (PR) or complete response. Plasma from seven healthy individuals was also collected as normal control. Exosomes were prepared by ultracentrifugation followed by total RNA extraction, and exosome-derived miRNAs were profiled using small RNA next-generation sequencing followed by differential expression analysis. RESULTS: In order to identify biomarker for better response, all five patients who achieved PR and four patients with progressive disease (PD) at efficacy evaluation were included for differential expression analysis. Based on unsupervised hierarchical clustering, exosomal miRNA expression profile was significantly altered in patients with NSCLC compared with normal controls with a total of 155 differentially expressed exosomal miRNAs. Interestingly, hsa-miR-320d, hsa-miR-320c, and hsa-miR-320b were identified significantly upregulated in the PD groups compared with the PR group at baseline before the treatment. In addition, we identified that hsa-miR-125b-5p, a T-cell suppressor, showed a trend of increased expression in the PD group at baseline and was significantly downregulated in the post-treatment plasma exosomes compared with pre-treatment samples of the PR patients. CONCLUSION: Patients with NSCLC represent unique plasma exosomal miRNA profiles. Hsa-miR-320d, hsa-miR-320c, and hsa-miR-320b were identified as potential biomarkers for predicting the efficacy of immunotherapy in advanced NSCLCs. When T-cell suppressor hsa-miR-125b-5p was downregulated during the treatment, the patients may obtain increased T-cell function and respond well to immunotherapy.

Benign disease prone to be misdiagnosed as malignant pulmonary nodules: Minute meningothelioid nodules.

BACKGROUND: The lung is one of the most common target organs for malignant tumor metastasis. The existence of lung metastasis may have a decisive effect on the choice of treatment regimen. Minute pulmonary meningothelial-like nodules (MPMNs) usually present as ground-glass opacity or solid nodules, mimicking the imaging findings of malignant pulmonary nodules. This study summarizes the clinical, radiological, and pathological features of MPMNs to distinguish them from malignant pulmonary nodules. METHODS: The Guangdong Lung Cancer Institute Pathology Information System was searched using the key words "minute meningothelioid nodules" and "lung." Patients who underwent pulmonary resection from 23 February 2009 to 31 May 2017 were included in the study. The 11th edition of Rosai and Ackerman's Surgical Pathology was used to confirm the diagnosis. The clinical, imaging, and pathological characteristics of MPMNs were recorded. RESULTS: Twelve patients had MPMNs. MPMNs were associated with cancerous or precancerous lesions (10/12), female gender (11/12), and non-smokers (11/12). Four patients were misdiagnosed with malignant pulmonary nodules before surgery. Positron emission tomography-computed tomography revealed an increased maximum standardized uptake value in one patient. Immunohistochemistry identified eight specimens positive for vimentin, EMA, and PR and negative for TTF-1 and CK. CONCLUSIONS: MPMNs tend to coexist with malignant tumors, mimicking the imaging findings of malignant pulmonary nodules, thus resulting in misdiagnosis. Dynamic monitoring or an invasive examination may help to distinguish MPMNs from malignant lesions.

EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China.

BACKGROUND: EGFR-tyrosine kinase inhibitors play an important role in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early-stage lung adenocarcinoma remain unclear. METHODS: We retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA-IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition. RESULTS: A total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early-stage and 949 to the advanced-stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced-stage group (P < 0.001). The total EGFR mutation rate in the early-stage group was similar to that in the advanced-stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early-stage and advanced-stage groups. CONCLUSION: Early-stage and advanced-stage groups exhibited the same EGFR mutation frequencies and types.

Liquid biopsy in non-small cell lung cancer: a key role in the future of personalized medicine?

INTRODUCTION: Liquid biopsies, especially the analysis of circulating tumor DNA (ctDNA), as a novel and non-invasive method for the diagnosis and monitoring of non-small cell lung cancer (NSCLC) have already been implemented in clinical settings. The majority of ctDNA is released from apoptotic or necrotic tumor cells, thus reflecting the genetic profile of a tumor. Numerous studies have reported a high concordance in mutation profiles derived from liquid biopsy and tissue biopsy, especially in driver genes. Liquid biopsy could overcome the clonal heterogeneity of tumour biopsy, as it provides a single snapshot of a tumour tissue. Moreover, non-invasiveness is the biggest advantage for liquid biopsy, and the procedure can be repeatedly performed during the treatment for the purpose of monitoring. Therefore, ctDNA could act as a potential complementary method for tissue biopsies in diagnosis, prognostic, treatment response and resistance. Areas covered: This review summarizes the recent advancements in liquid biopsy with a focus on NSCLC, including its applications and technologies associated with assessing ctDNA. The authors conclude the review by discussing the challenges associated with liquid biopsy. Expert commentary: The analysis of ctDNA represents a promising method for liquid biopsy, which will be a novel and potentially complementary method in diagnosis, treatment and prognostic in NSCLC at all stages.

Giant Serpentine Middle Cerebral Artery Aneurysm.

Giant serpentine aneurysms are rare entity, which have unique presentations and distinct angiographic features, with poor prognosis if not treated. In this paper, a patient with a giant serpentine aneurysm originated from right middle cerebral artery was reported. A 38-year-old woman suffered from progressively headache and vision declined. The computed tomography and magnetic resonance image revealed a partially calcified, large mass (approximately 80 × 70 × 60 mm sized) in the right frontal-temple lobe. On computed tomography angiography, an unruptured, giant, partially thrombosed, serpentine aneurysm was confirmed. After treatment by craniotomy, the patient was rehabilitation. Operation is an effective method for the treatment of giant serpentine aneurysms. In addition, cerebral angiography and balloon test occlusion are the crucial way of preoperative assessment.

Cigarette smoking and risk of adult glioma: a meta-analysis of 24 observational studies involving more than 2.3 million individuals.

BACKGROUND: Cigarette smoking has been shown to be a risk factor for adult glioma by some but not all studies. We conducted a meta-analysis to systematically assess the potential association. METHODS: PubMed and EMBASE were searched from the date of their inception to October 1, 2015, to identify relevant articles. Reference lists from these articles were reviewed to identify additional studies. Both cohort and case-control studies were included. Fixed-effects models were used to calculate the overall relative risk (RR) with corresponding 95% confidence intervals (CIs). RESULTS: The final analysis included 24 studies (seven cohort and 17 case-control studies), involving more than 2.3 million individuals. The combined RR was 1.04 (95% CI: 1.00, 1.09; P=0.073) for ever-smokers, 0.97 (95% CI: 0.88, 1.07; P=0.574) for current-smokers, and 1.07 (95% CI: 0.98, 1.16; P=0.130) for past smokers, with little evidence of heterogeneity. Omission of any single study from the analysis had little effect on the result. No evidence of publication bias was found. A small but statistically significant increase was found in past smokers in females (RR: 1.13, 95% CI: 1.00, 1.28; P=0.046) but not in males. CONCLUSION: In general, there was no association between cigarette smoking and adult glioma. The small but statistically significant association in females requires further investigation.