Modified subxiphoid thoracoscopic thymectomy for early-stage thymic tumor: case report.

Background: Minimally invasive thymectomy via subxiphoid is increasingly being used for thymic tumors. Limited by the small space behind the sternum, the subxiphoid approach is sometimes difficult to perform. In this study, we introduce a modified subxiphoid thoracoscopic thymectomy which is performed via subxiphoid approach using an auxiliary sternal retractor to elevate the sternal to create a larger space behind the sternum. Therefore, the phrenic nerves on both sides were revealed more clearly and the left innominate vein was mobilized safer and easier. Case Description: This study describes the treatment process of a 27-year-old female patient with an incidental finding of a thymic mass. Chest contrast computed tomography revealed a 35 mm × 25 mm lesion in the anterior mediastinum which might be adherent to the left innominate vein. A careful preoperative evaluation was well done and no contraindications to the operation were found. This patient underwent modified subxiphoid thoracoscopic thymectomy, successfully completed without complications occurred during the perioperative period. The patient was discharged home well on post-operative day 2. The pathological diagnosis was mature teratoma. Conclusions: In conclusion, modified subxiphoid thoracoscopic thymectomy using an auxiliary sternal retractor makes minimally invasive thymectomy safer and simpler and is an alternative option for patients with early-stage thymic tumors.

ASCC3 promotes the immunosuppression and progression of non-small cell lung cancer by impairing the type I interferon response via CAND1-mediated ubiquitination inhibition of STAT3.

BACKGROUND: Activating signal cointegrator 3 (ASCC3) has been identified as an oncogenic factor that impairs host immune defense. However, the underlying mechanisms of carcinogenesis and its impact on the antitumor immune response remain unclear. In this study, we aimed to investigate the molecular mechanisms of ASCC3 in the progression of non-small cell lung cancer (NSCLC). METHODS: Single-cell sequencing data from the Gene Expression Omnibus and gene expression profiles from The Cancer Genome Atlas database were analyzed. The expression, clinical relevance and biological functions of ASCC3 in NSCLC were explored. Then, RNA sequencing, immunoprecipitation, mass spectrometry, immunofluorescence, and flow cytometry analyses were conducted to explore the underlying molecular mechanisms. In addition, in vivo experiments in mouse models were conducted to explore the probability of ASCC3 knockdown to improve the efficacy of anti-Programmed Death-1 (PD-1) therapy in NSCLC. RESULTS: ASCC3 was significantly upregulated in NSCLC and correlated with poor pathological characteristics and prognosis in patients with NSCLC. Overexpression of ASCC3 promoted malignant phenotypes of NSCLC cells and induced an immunosuppressive tumor microenvironment, which was characterized by a decrease in CD8+ T cells, natural killer cells and dendritic cells but an increase in regulatory T(Treg) cells. Mechanistically, ASCC3 stabilized signal transducer and activator of transcription (STAT)3 signaling by recruiting Cullin-associated and neddylation dissociated 1 (CAND1), which inhibited ubiquitin-mediated degradation of STAT3, thereby impairing the type I interferon response of tumor cells and promoting the immunosuppression and progression of NSCLC. Furthermore, high expression of ASCC3 impaired the efficacy of anti-PD-1 therapy, and an anti-PD-1 antibody combined with ASCC3 knockdown exerted promising synergistic efficacy in a preclinical mouse model. CONCLUSION: ASCC3 could stabilize the STAT3 pathway via CAND1, reshaping the tumor microenvironment and inducing resistance to anti-PD-1 therapy, which promotes the progression of NSCLC. It is a reliable prognostic indicator and can be a target in combination therapy for NSCLC.

Comprehensive landscape and future perspective of long noncoding RNAs in non-small cell lung cancer: it takes a village.

Long noncoding RNAs (lncRNAs) are a distinct subtype of RNA that lack protein-coding capacity but exert significant influence on various cellular processes. In non-small cell lung cancer (NSCLC), dysregulated lncRNAs act as either oncogenes or tumor suppressors, contributing to tumorigenesis and tumor progression. LncRNAs directly modulate gene expression, act as competitive endogenous RNAs by interacting with microRNAs or proteins, and associate with RNA binding proteins. Moreover, lncRNAs can reshape the tumor immune microenvironment and influence cellular metabolism, cancer cell stemness, and angiogenesis by engaging various signaling pathways. Notably, lncRNAs have shown great potential as diagnostic or prognostic biomarkers in liquid biopsies and therapeutic strategies for NSCLC. This comprehensive review elucidates the significant roles and diverse mechanisms of lncRNAs in NSCLC. Furthermore, we provide insights into the clinical relevance, current research progress, limitations, innovative research approaches, and future perspectives for targeting lncRNAs in NSCLC. By summarizing the existing knowledge and advancements, we aim to enhance the understanding of the pivotal roles played by lncRNAs in NSCLC and stimulate further research in this field. Ultimately, unraveling the complex network of lncRNA-mediated regulatory mechanisms in NSCLC could potentially lead to the development of novel diagnostic tools and therapeutic strategies.

Detection of Epstein-Barr virus infection in thymic epithelial tumors by nested PCR and Epstein-Barr-encoded RNA ISH.

BACKGROUND: Epstein-Barr virus (EBV) is well known to be associated with a lot of tumors, including lymphoma, nasopharyngeal carcinoma, EBV-associated gastric carcinoma, and some other carcinomas with similar lymphoepithelioma-like features. However, the association between EBV and thymic epithelial tumors (TETs) is inconclusive as reports in this regard are not entirely consistent and the methods employed are of different sensitivity and specificity. The geographical difference of the patients is also one of the reasons for the different points of view. METHODS: In our study, we examined 72 thymomas, including 3 cases of type A thymomas, 27 cases of type AB, 6 cases of type B1, 26 cases of type B2 and 10 cases of type B3 thymomas, and 15 thymic carcinomas to detect the viral genome at both DNA and RNA levels. The genome DNA of fresh tissues was first screened by nested polymerase chain reaction (PCR), which could be regarded as the most sensitive method to detect small amounts of DNA. Then all the tissue blocks were further submitted for viral localization by Epstein-Barr-encoded RNA (EBER) ISH. Group parameters were assessed using the chi-square test at a significance level of p < 0.05. RESULTS: Nested PCR results showed that none of type A, eight (29.6%) type AB, one (16.7%) type B1, fifteen (57.7%) type B2, and four (40.0%) type B3 were positive for EBV genome. However, none of them detected EBER expression except for one case of type B2 thymoma. Fourteen (93.3%) thymic carcinomas were positive for EBV by nested PCR, of which three displayed weak nuclear signals within the tumor cells by EBER ISH. CONCLUSIONS: These results showed that nested PCR was a sensitive method for screening the EBV genome in thymic epithelial tumors. As the malignancy of thymoma increases, the rate of EBV infection became higher. Thymic carcinomas were well associated with the Epstein-Barr virus.There was significant association between the EBV infection rate and thymoma type (p < 0.05). We further analyzed the association between EBV infection and myasthenia gravis. However, it showed no significant difference(p = 0.2754), although the EBV infection rate was higher in the thymomas with myasthenia gravis.

Prognostic Correlation between Tumor Volume and Complete Resection of Thymoma at Different Masaoka-Koga Stages.

OBJECTIVE: Thymoma is a slow-growing epithelial tumor of thymus gland. Its size is associated with its prognosis. The aim of this study was to analyze the prognostic correlation of tumor volume and complete resection of thymoma at different Masaoka-Koga stages. METHODS: A retrospective study was carried out, using the data of 502 patients who underwent complete resection of thymectomy at Zhongshan Hospital, Fudan University, in Shanghai, China, from February 2009 to February 2016. The characteristics of the patients were collected. Using Masaoka-Koga staging system, patients were divided into four different subcohorts: Stage I, stage II, stage III and stage IVa/IVb. The relationship between tumor volume and postoperative recurrence was analyzed for each subcohort, using receiver operating curves, cutoff values were obtained. and patients were grouped according to the cutoff values. Survival analysis was performed with the help of Kaplan-Meier method, and the difference between the two survival curves was compared using log-rank test. Whether tumor volume could be used as an independent risk factor for thymoma prognosis was analyzed, using a univariate Cox proportional hazards model. RESULTS: The area under the curve was 0.718, 0.740, 0.798, and 0.804 for the stage I, II, III, and IVa/IVb subcohorts, respectively, and the cutoff values of tumor volume for predicting recurrence were 47.90 cm3, 53.70 cm3, 76.35 cm3, and 89.05 cm3, respectively. Patients with tumor volumes greater than the cutoff values had significantly shorter recurrence-free survival than those with tumor volumes less than the cutoff values (p < 0.001). The results of the univariate Cox proportional hazards model indicated that tumor volume was an independent risk factor for thymoma prognosis and for postoperative prognosis of thymoma in Masaoka-Koga stage I (p < 0.001). CONCLUSIONS: Tumor volume is significantly correlated with the postoperative prognosis of thymoma in Masaoka-Koga stage I and can serve as an independent risk factor for predicting postoperative tumor recurrence.

Tumor-infiltrating CD36+CD8+T cells determine exhausted tumor microenvironment and correlate with inferior response to chemotherapy in non-small cell lung cancer.

BACKGROUND: The scavenger receptor CD36 was reported to be highly expressed on tumor-infiltrating CD8+ T cells, but the clinical role remains obscure. This study aims to explore the infiltration and clinical value of CD36+CD8+ T cells in NSCLC. METHODS: Immunohistochemistry and immunofluorescence were conducted for survival analyses and immunological evaluation in 232 NSCLC patients in Zhongshan Hospital. Flow cytometry analyses were carried out to assess the immune cells from fresh tumor samples, non-tumor tissues and peripheral blood. In vitro tumor infiltrating lymphocytes cultures were conducted to test the effect of CD36 blockage. RESULTS: Accumulation of CD36+CD8+ T cells in tumor tissues was correlated with more advanced stage (p < 0.001), larger tumor size (p < 0.01), and lymph node metastasis (p < 0.0001) in NSCLC. Moreover, high infiltration of CD36+CD8+ T cells indicated poor prognosis in terms of both overall survival (OS) and recurrence-free survival (RFS) and inferior chemotherapy response. CD36+CD8+ T cells showed decreased GZMB (p < 0.0001) and IFN-γ (p < 0.001) with elevated PD-1 (p < 0.0001) and TIGIT (p < 0.0001). Analysis of tumor-infiltrating immune cell landscape revealed a positive correlation between CD36+CD8+ T cells and Tregs (p < 0.01) and M2-polarized macrophages (p < 0.01) but a negative correlation with Th1 (p < 0.05). Notably, inhibition of CD36 partially restored the cytotoxic function of CD8+ T cells by producing more GZMB and IFN-γ. CONCLUSION: CD36+CD8+ T cells exhibit impaired immune function and high infiltration of CD36+CD8+ T cells indicated poor prognosis and inferior chemotherapy response in NSCLC patients. CD36 could be a therapeutic target in combination with chemotherapy in NSCLC patients.

Immunotherapy of thymic epithelial tumors: molecular understandings and clinical perspectives.

Immunotherapy has emerged to play a rapidly expanding role in the treatment of cancers. Currently, many clinical trials of therapeutic agents are on ongoing with majority of immune checkpoint inhibitors (ICIs) especially programmed death receptor 1 (PD-1) and its ligand 1 (PD-L1) inhibitors. PD-1 and PD-L1, two main immune checkpoints, are expressed at high levels in thymic epithelial tumors (TETs) and could be predictors of the progression and immunotherapeutic efficacy of TETs. However, despite inspiring efficacy reported in clinical trials and clinical practice, significantly higher incidence of immune-related adverse events (irAEs) than other tumors bring challenges to the administration of ICIs in TETs. To develop safe and effective immunotherapeutic patterns in TETs, understanding the clinical properties of patients, the cellular and molecular mechanisms of immunotherapy and irAEs occurrence are crucial. In this review, the progress of both basic and clinical research on immune checkpoints in TETs, the evidence of therapeutic efficacy and irAEs based on PD-1 /PD-L1 inhibitors in TETs treatment are discussed. Additionally, we highlighted the possible mechanisms underlying irAEs, prevention and management strategies, the insufficiency of current research and some worthy research insights. High PD-1/PD-L1 expression in TETs provides a rationale for ICI use. Completed clinical trials have shown an encouraging efficacy of ICIs, despite the high rate of irAEs. A deeper mechanism understanding at molecular level how ICIs function in TETs and why irAEs occur will help maximize the immunotherapeutic efficacy while minimizing irAEs risks in TET treatment to improve patient prognosis.

Exosomal circZNF451 restrains anti-PD1 treatment in lung adenocarcinoma via polarizing macrophages by complexing with TRIM56 and FXR1.

BACKGROUND: Although success was achieved in the therapy for a minority of advanced lung adenocarcinoma (LUAD) patients, anti-programmed death 1 (PD1) resistance was found in most LUAD patients. Here, we aimed to uncover a potential role of exosomal circular RNAs (circRNAs) in LUAD refractory to PD1 blockade.  METHODS: circRNA sequencing and qRT-PCR were performed to determine the level of exosomal circRNAs in LUAD patients subsequently treated with anti-PD1. Then, the RNA pulldown, RNA immunoprecipitation, mass spectrometry, chromatin immunoprecipitation, luciferase reporter assays, flow cytometry, RNA sequencing, and in vitro and in vivo models were used to uncover the biological functions and underlying mechanism of circZNF451 in LUAD anti-PD1 treatment resistance. RESULTS: circRNA sequencing and qRT-PCR identified the up-regulation of exosomal circZNF451 from LUAD patients with progressive disease (PD) compared to those with partial remission (PR) after PD1 blockade therapy. Furthermore, elevated circZNF451 was revealed to be associated with poor prognosis of LUAD patients. Additionally, exosomal circZNF451 was demonstrated to induce an anti-inflammatory phenotype in macrophages and exhaustion of cytotoxic CD8+ T cells, and enhanced TRIM56-mediated degradation of FXR1 to activate the ELF4-IRF4 pathway in macrophages. By transgenic mice, knockout of ELF4 in macrophages was found to rescue immunotherapy efficacy in tumors with high level of exosomal circZNF451. CONCLUSION: Exosomal circZNF451 reshapes the tumor immune microenvironment by inducing macrophages polarization via the FXR1- ELF4-IRF4 axis and is a novel biomarker for predicting the sensitivity of PD1 blockade in LUAD.

Elevated circASCC3 limits antitumor immunity by sponging miR-432-5p to upregulate C5a in non-small cell lung cancer.

Although anti-programmed cell death 1 (PD1) treatment has become a first-line therapy for advanced non-small cell lung cancer (NSCLC), most NSCLC patients are refractory to anti-PD1. Here, we aimed to investigate the mechanism of dysregulated circular RNAs (circRNAs) related to anti-PD1 resistance in NSCLC. The expression of circASCC3 (hsa_circ_0077,495) in NSCLC tissues and cell lines was evaluated by fluorescence in situ hybridization and quantitative reverse transcription-polymerase chain reaction. The functions and mechanisms of circASCC3 in NSCLC progression and anti-PD1 resistance were uncovered in vitro and in vivo. The circASCC3 level was upregulated in NSCLC compared with that in paired normal tissues. Specifically, circASCC3 expression was higher in tissues from NSCLC patients with anti-PD1 refractory than in those from patients who sensitive to anti-PD1. Overexpression of circASCC3 enhanced the malignant phenotype of NSCLC cells and led to an immunosuppressive microenvironment. Mechanistically, circASCC3 sponged miR-432-5p to increase complement C5a levels, which enhanced the progression and dysfunctional immune status of NSCLC. Thus, circASCC3 overexpression reshapes the tumor microenvironment by impacting the complement system in NSCLC and provides a potential strategy to overcome anti-PD1 resistance.

Recent thymic emigrants as the bridge between thymoma and autoimmune diseases.

Recent thymic emigrants (RTEs) are naïve T cells that egress the thymus following intrathymic development. This continuous process, including self-renewal, is crucial to establish and maintain human immune function. Several biomarkers can identify RTEs, but none of them is specific. Additional methods to detect and study RTEs phenotypically and functionally revealed alterations in RTEs in various adverse health conditions, including autoimmune diseases, systemic disorders and thymic abnormalities such as thymoma. Often associated with autoimmune disease, thymoma is the only tumor that can generate RTEs. However, a causal relationship between RTEs and autoimmune disease remains uncertain. Here, we review current knowledge about the connections between thymoma, RTEs and autoimmune diseases to provide new perspectives for therapeutic strategies.

Circulating tumor cell methylation profiles reveal the classification and evolution of non-small cell lung cancer.

Background: The ability of circulating tumor cells (CTCs) to identify lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) could improve pathological diagnosis and the selection of treatments for non-small cell lung cancer (NSCLC). Previous studies have shown that deoxyribonucleic acid (DNA) methylation exhibits cell and tissue specificity. Thus, we aimed to explore the methylation status of CTCs in LUAD and LUSC and identify the potential biomarkers. Methods: We first analyzed Infinium 450K methylation profiles obtained from The Cancer Genome Atlas and Gene Expression Omnibus. We then performed whole-genome sequencing of CTCs in tumor and matched normal lung tissues and white blood cells from 6 NSCLC patients. Results: The bioinformatics analysis revealed a NSCLC-specific DNA methylation marker panel, which could accurately distinguish between LUAD and LUSC with high diagnostic accuracy. The whole-genome sequencing of CTCs in NSCLC patients also showed 100% accuracy for distinguishing between LUAD and LUSC based on the CTC methylation profiles. To investigate the function of CTCs, we further analyzed similar and different methylation profiles between the CTCs and their primary tumors, and found very high similarities between the CTCs and their primary tumor tissues, indicating that these cells inherit information from primary tumors. However, the CTCs also displayed some characteristics that differed to those of primary tumor tissues, which suggest that CTCs acquire some unique characteristics after migrating from the primary tumor; these characteristics may partly explain the ability of tumor cells to evade immune surveillance. Conclusions: Our findings provide insights into the potential use of CTCs in the pathological classification of NSCLC patients. Our findings also show how CTC primary tumor inheritance and CTC evolution affect metastasis and immune escape.

Minimally invasive thymectomy for myasthenia gravis: a 7-year retrospective study.

BACKGROUND: Thymectomy has been identified as an effective strategy for patients with myasthenia gravis (MG) and thymic masses. However, the best surgical approach remains a matter of debate. The aim of the present study was to compare the surgical and neurological outcomes of video-assisted thoracoscopic thymectomy with a modified subxiphoid and bilateral approach in patients with MG and thymic masses. METHODS: From August 2013 to April 2018, 68 patients who were diagnosed with MG and thymic masses and underwent video-assisted thoracoscopic thymectomy with a modified subxiphoid (44 patients) or bilateral (24 patients) approach were included in this retrospective study. The surgical and neurological results were analyzed with propensity score matching. RESULTS: After propensity score matching, the modified subxiphoid approach in video-assisted thoracoscopic thymectomy resulted in an obviously shorter operative time (P=0.00), drainage duration (P=0.00), less intraoperative blood loss (P=0.00), and shorter postoperative hospital stay (P=0.01). In terms of neurological outcomes, no significant difference was observed in the improvement in MG, with 2-year complete stable remission rates of 21.1% and 26.3% (P=0.68) and 2-year pharmacological remission rates of 31.6% and 26.3% (P=0.60) for the bilateral and subxiphoid approaches, respectively. Additionally, the approaches resulted in similar effects on the magnitudes of decrease in the prednisolone and pyridostigmine doses after 2 years, with average pyridostigmine dose reductions of 72.2% and 71.1% (P=0.78) and average prednisolone reductions of 76.8% and 71.7% (P=0.96) for the bilateral and subxiphoid approaches, respectively. CONCLUSIONS: The modified subxiphoid approach was found to be superior to the bilateral approach in video-assisted thoracic surgery thymectomy in terms of the surgical outcomes and yielded similar neurological outcomes. Therefore, the modified subxiphoid approach is recommended as an alternative to the bilateral approach in the treatment of patients with MG and thymic masses.

Modified Subxiphoid Thoracoscopic Thymectomy for Locally Invasive Thymoma.

BACKGROUND: We explored the feasibility and safety of modified subxiphoid thoracoscopic thymectomy for patients with locally invasive thymomas. METHODS: Subxiphoid thoracoscopic thymectomy was performed on select patients with locally invasive thymomas (Masaoka stage III) using an auxiliary sternal retractor to create a larger operative field. RESULTS: From June 2015 to March 2019, we performed modified subxiphoid thoracoscopic thymectomy on 48 patients with locally invasive thymomas: 39 patients had pericardium or lung infiltration and received a combination of a partial pericardium or lung wedge resection, and 9 patients had left innominate vein infiltration and underwent combined resection of the left innominate vein. Thoracoscopic thymectomy was performed from the subxiphoid pathway with an auxiliary sternal retractor in all 48 patients, and there were no conversions to median sternotomy. The median tumor size was 5 cm, and the maximal tumor size was 12 cm. The median blood loss was 50 mL. The median duration of chest tube placement was 3 days, and the median hospital stay was 4.5 days after surgery. All patients achieved a good recovery after surgery, and none had serious complications during the perioperative period. All patients underwent postoperative adjuvant radiotherapy and presented no local recurrence or distant metastasis until now. CONCLUSIONS: Modified subxiphoid thoracoscopic thymectomy with an auxiliary sternal retractor makes minimally invasive thymectomy easier and safer to perform and is an alternative approach for some patients with locally invasive thymomas.

Downregulation of SETBP1 promoted non-small cell lung cancer progression by inducing cellular EMT and disordered immune status.

PURPOSE: SET binding protein 1 (SETBP1) has involved in cancer pathogenesis like leukemic malignancies and breast cancer. But the role and the underlying mechanism in NSCLC remain unclear. METHODS: RT-PCR and western blotting were used for determining the expression level of SETBP1 in NSCLC. The clinical values of SETBP1 expression were evaluated by tissue microarray and immunohistochemistry. CCK-8, transwell and Matrigel assays were used to assess NSCLC cells proliferation, migration and invasion ability. The analysis of EMT markers was carried out by RT-PCR, western blotting and immunofluorescence. Bioinformatics analysis revealed the relationship between SETBP1 expression and tumor-associated immune cells. RESULTS: SETBP1 expression was significantly downregulated in NSCLC tissues than matched peri-tumors and NSCLC patients with the decreased level of SETBP1 had worse OS. Downregulation of SETBP1 expression induced EMT to promote NSCLC cells proliferation, migration and invasion by the activation of ERK1/2 signal pathway. Aberrant SETBP1 expression was companied by disordered immune status of NSCLC patients and might be involved in regulation of polarization of tumor-associated macrophages. CONCLUSION: SETBP1 can act as a tumor suppressor to reduce the progression of NSCLC and can be used for a prognostic biomarker in NSCLC. Aberrant SETBP1 expression was companied by disordered immune status of NSCLC patients.

Overexpression of EI2BL promoted human non-small cell lung cancer progression by inducing cell EMT phenotype.

AIMS: To unveil the role of EI2BL in non-small cell lung cancer (NSCLC) and the relationship between expression of EI2BL and the prognosis of patients with NSCLC. METHODS: Immunohistochemistry (IHC), western blot analysis, immunofluorescence and real-time quantitative PCR (RT-qPCR) were used to evaluate EI2BL protein and mRNA levels in NSCLC and corresponding peritumour tissues. Cell Counting Kit-8, transwell assay and wound healing assay were used to analyse the abilities of cell proliferation, invasion and migration. In addition, the analysis of epithelial-mesenchymal transition (EMT) markers was also assessed by western blot analysis, RT-qPCR and immunofluorescence. Tissue micro-array analysis of 200 NSCLC cases was used to assess the relationship between EI2BL expression and clinicopathological characteristics. Moreover, the prognostic role of EI2BL in 200 patients with NSCLC was evaluated by Cox regression models and Kaplan-Meier methods. RESULTS: Elevated EI2BL expression was more common in NSCLC tissues than paired peritumour tissues in both mRNA and protein level. EI2BL promoted the proliferation, invasion and migration of NSCLC cells. In addition, aberrant EI2BL expression might modulate the expression of key molecules of EMT by ERK1/2 signal pathway. The expression of EI2BL was significantly associated with tumour stage, lymph node metastasis and tumour size. Moreover, higher expression of EI2BL in patients with NSCLC had a poor overall survival rate. CONCLUSIONS: Our study illustrated that elevated expression of EI2BL promoted NSCLC cell proliferation, migration and invasion and EI2BL overexpression may be a reliable biomarker of poor prognosis.

Comparison between CT and MRI in the Diagnostic Accuracy of Thymic Masses.

Purpose: The aim of this study was to compare diagnostic accuracy between CT and MRI for thymic masses. Methods: We searched literature and collected information on first author, publication year, cases of different types of thymic lesions, correct diagnostic cases of CT and MRI and results of quantitative analysis of CT and MRI. The ROC curve was applied to compare the diagnostic performance of different imaging modalities. Results: Eight literatures were finally included and analyzed in this study. There were 253 cases examined by CT and 340 cases by MRI in total. We showed outcomes of quantitative analysis of each study in this article. The sensitivity of CT and MRI was both 100%, while the specificity was 75% and 80%, respectively. AUC of CT was 0.875 [95%CI: 0.473, 0.997] and that of MRI was 0.880 [95%CI: 0.531, 0.995]. Conclusion: The diagnostic accuracy of MRI is superior to CT in detecting thymomas, thymic cysts or thymic hyperplasia but that of CT and MRI is still unclear in differentiating thymic carcinomas and lymphomas/germ cell tumors.

A mutational profile in multiple thymic squamous cell carcinoma.

BACKGROUND: Multiple thymic squamous cell carcinoma (TSCC) is a rare thymic epithelial tumor with a dismal prognosis. Mutational profiles of multiple TSCC may expand our understanding of tumorigenesis and treatment options for these tumors. METHODS: We sequenced the whole exomes of 3 TSCC nodules from a multiple TSCC patient and a paired peripheral blood sample and identified single-nucleotide variants and small insertions and deletions, and also performed gene ontological and pathway analyses. RESULTS: The 3 TSCC nodules were subjected to hematoxylin-eosin staining, and the results showed that these 3 nodules were highly similar with respect to histology. We identified 116, 94 and 98 non-synonymous somatic mutations in the 3 TSCC nodules, and 34 mutations, including mutations in TP53 and ARID1A, among others, were present in all 3 TSCC nodules. We then performed immunohistochemistry to assess two selected genes, TP53 and ARID1A, and found that the 3 TSCC nodules expressed similar levels of TP53 and ARID1A. Further gene ontological analysis and pathway analysis revealed that the 3 TSCC nodules also had similar significantly enriched pathways based on the identified genetic alterations. These results demonstrated that the 3 multiple TSCC nodules were spatially independent of each other but were highly similar with respect to histological sources and genetic characteristics, suggesting that 2 TSCC nodules were likely metastases of the third nodule. CONCLUSIONS: These findings suggest that TSCC cells can be transferred to other sites inside the thymus and that total thymectomy is a good treatment option for thymic epithelial tumors.

Loss of UHRF2 Is Associated With Non-small Cell Lung Carcinoma Progression.

Recent evidence indicated ubiquitin like with PHD and ring finger domains 2 (UHRF2) was involved in various human diseases, especially in cancer, however, its roles in cancer are still in dispute. Here, we found UHRF2 expression was decreased in lung cancer tissues compared with adjacent normal tissues by referring to the Oncomine Database, which was further identified by immunoblotting and quantitative real-time polymerase chain reaction assays. Secondly, we found knockdown of UHRF2 in A549 and 95-D cell lines enhanced the capability of proliferation, invasion and migration, while forced UHRF2 expression inhibited NSCLC cells proliferation,invasion and migration. Mechanistically, dot-blot and western blot assays indicated that the level of UHRF2 was positively correlated with 5-hmC level by affecting ten-eleven translocation 2 (TET2) expression. Clinically, UHRF2 downregulation is significantly correlated with a malignant phenotype, including larger tumor size and poor differentiation. Moreover, UHRF2 downregulated correlates with shorter overall survival(OS). Conclusion: Our findings indicate that UHRF2 is a tumor suppressor in NSCLC by influence TET2 expression and serve as a potential therapeutic target in NSCLC.