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Medical Science Monitor : International... Jul 2021BACKGROUND Thymoma is the most common tumor of the anterior mediastinum, and can be caused by infrequent malignancies arising from the epithelial cells of the thymus....
BACKGROUND Thymoma is the most common tumor of the anterior mediastinum, and can be caused by infrequent malignancies arising from the epithelial cells of the thymus. Unfortunately, blood-based diagnostic markers are not currently available. High-throughput sequencing technologies, such as RNA-seq with next-generation sequencing, have facilitated the detection and characterization of both coding and non-coding RNAs (ncRNAs), which play significant roles in genomic regulation, transcriptional and post-transcriptional regulation, and imprinting and epigenetic modification. The knowledge about fusion genes and ncRNAs in thymomas is scarce. MATERIAL AND METHODS For this study, we gathered large-scale RNA-seq data belonging to samples from 25 thymomas and 25 healthy thymus specimens and analyzed them to identify fusion genes, lncRNAs, and miRNAs. RESULTS We found 21 fusion genes, including KMT2A-MAML2, HADHB-REEP1, COQ3-CGA, MCM4-SNTB1, and IFT140-ACTN4, as the most frequent and significant in thymomas. We also detected 65 differentially-expressed lncRNAs in thymomas, including AFAP1-AS1, LINC00324, ADAMTS9-AS1, VLDLR-AS1, LINC00968, and NEAT1, that have been validated with the TCGA database. Moreover, we identified 1695 miRNAs from small RNA-seq data that were overexpressed in thymomas. Our network analysis of the lncRNA-mRNA-miRNA regulation axes identified a cluster of miRNAs upregulated in thymomas, that can trigger the expression of target protein-coding genes, and lead to the disruption of several biological pathways, including the PI3K-Akt signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. CONCLUSIONS Our results show that overexpression of this miRNA cluster activates PI3K-Akt, FoxO, HIF-1, and Rap-1 signaling pathways, suggesting pathway inhibitors may be therapeutic candidates against thymoma.
Topics: Adult; Aged; Biomarkers, Tumor; Female; Humans; Male; Middle Aged; RNA, Long Noncoding; Thymoma; Thymus Neoplasms
PubMed: 34219124
DOI: 10.12659/MSM.929727 -
Thoracic Cancer May 2023This study aimed to examine the treatment and prognosis of patients with type B2 + B3 thymoma and compare it with those patients with type B2 and B3 thymoma.
BACKGROUND
This study aimed to examine the treatment and prognosis of patients with type B2 + B3 thymoma and compare it with those patients with type B2 and B3 thymoma.
METHODS
We conducted a retrospective analysis of the results of 39 patients with type B2 + B3 thymoma, 133 patients with type B2 thymoma, and 64 patients with type B3 thymoma. The Kaplan-Meier technique was used to generate survival curves. For multivariate analysis, the Cox proportional hazard model was applied.
RESULTS
With a median follow-up of 60 months (range: 1-128 months), the percentage of patients with tumor, node, metastasis (TNM) stage III and IV disease gradually increased from 19.5% to 25.6% to 35.9% among those with histological subtypes B2, B2 + B3, and B3, respectively, p = 0.045. Twenty-three patients experienced recurrence or metastasis. The total 10-year progression-free survival (PFS) rates were 86.0% overall (85.0% in type B2, 87.2% in type B2 + B3, and 87.5% in type B3). Age, R0 resection, and Masaoka-Koga stage were found to have a significant on PFS in all patients. There was no statistically significant difference in PFS between different histotypes of thymoma, p = 0.650. PFS was predicted by R0 resection in all histotypes and by the Masaoka-Koga stage in the type B2 subgroup.
CONCLUSION
Combining the two staging methods to guide the diagnosis and treatment of patients with B2 + B3 thymoma is recommended. R0 resection is recommended to reduce recurrence. Patients with B2 + B3 thymoma have a prognosis similar to those with a B2 thymoma or a B3 thymoma alone.
Topics: Humans; Thymoma; Retrospective Studies; Thymus Neoplasms; Prognosis; Progression-Free Survival; Neoplasm Staging; Treatment Outcome
PubMed: 37037477
DOI: 10.1111/1759-7714.14875 -
Thoracic Cancer Dec 2022Thymic epithelial tumors (TET) are a group of rare neoplasms of the anterior mediastinum comprising thymomas and thymic carcinomas. The carcinogenesis of TET is mostly... (Review)
Review
Thymic epithelial tumors (TET) are a group of rare neoplasms of the anterior mediastinum comprising thymomas and thymic carcinomas. The carcinogenesis of TET is mostly unknown. Many studies, mostly retrospective case series, have tried to establish prognostic factors in TET. TET is a very heterogeneous group of tumors with many subtypes for which diagnosis and treatment remains a very challenging task. Despite the disparities among retrospective studies, there are some prognostic factors that are more pertinent such as the completeness of resection, TNM stage and the Masaoka-Koga classification. On the other hand, the identification of different genetic pathways that result in the pathogenesis of TET represents a fascinating field of study that could possibly lead to the development of new targeted therapies. The aim of this review is to discuss the different prognostic factors and genetic markers of TET. The meticulous use of national and international databases could provide sufficient number of patients in order to draw more valid conclusions.
Topics: Humans; Prognosis; Retrospective Studies; Genetic Markers; Neoplasm Staging; Thymus Neoplasms; Thymoma; Neoplasms, Glandular and Epithelial
PubMed: 36349433
DOI: 10.1111/1759-7714.14725 -
Cancers Apr 2023Thymic carcinoma is an aggressive malignancy that can be challenging to distinguish from thymoma using histomorphology. We assessed two emerging markers for these...
Thymic carcinoma is an aggressive malignancy that can be challenging to distinguish from thymoma using histomorphology. We assessed two emerging markers for these entities, EZH2 and POU2F3, and compared them with conventional immunostains. Whole slide sections of 37 thymic carcinomas, 23 type A thymomas, 13 type B3 thymomas, and 8 micronodular thymomas with lymphoid stroma (MNTLS) were immunostained for EZH2, POU2F3, CD117, CD5, TdT, BAP1, and MTAP. POU2F3 (≥10% hotspot staining), CD117, and CD5 showed 100% specificity for thymic carcinoma versus thymoma with 51%, 86%, and 35% sensitivity, respectively, for thymic carcinoma. All POU2F3 positive cases were also positive for CD117. All thymic carcinomas showed >10% EZH2 staining. EZH2 (≥80% staining) had a sensitivity of 81% for thymic carcinoma and a specificity of 100% for thymic carcinoma versus type A thymoma and MNTLS but had poor specificity (46%) for thymic carcinoma versus B3 thymoma. Adding EZH2 to a panel of CD117, TdT, BAP1, and MTAP increased cases with informative results from 67/81 (83%) to 77/81 (95%). Overall, absent EZH2 staining may be useful for excluding thymic carcinoma, diffuse EZH2 staining may help to exclude type A thymoma and MNTLS, and ≥10% POU2F3 staining has excellent specificity for thymic carcinoma versus thymoma.
PubMed: 37190202
DOI: 10.3390/cancers15082274 -
Journal of Orthopaedic Case Reports Apr 2023While metastases of malignant thymomas have been shown, type A thymomas are often treated as benign. Type A thymomas often have excellent response to treatment, low...
INTRODUCTION
While metastases of malignant thymomas have been shown, type A thymomas are often treated as benign. Type A thymomas often have excellent response to treatment, low recurrence rate, and a small malignant potential. To date, there have been no reports of type A thymomas with spinal metastases.
CASE REPORT
A 66-year-old female with a type A thymoma metastatic to the T7 and T8 vertebral bodies and brain, with associated pathologic burst fracture, collapse of T7, and significant focal kyphosis . The patient underwent successful T7-T8 posterior corpectomy and T4-T11 posterior spinal fusion. At 2 years of follow-up, she was ambulating without assistive devices and completed spinal radiation and initial chemotherapy.
CONCLUSION
Metastatic type A thymoma is a rare phenomenon. While traditionally thought to have low recurrence rates and overall excellent survival rates, our case suggests that the biologic malignant potential of a type A thymoma may not be fully understood.
PubMed: 37193387
DOI: 10.13107/jocr.2023.v13.i04.3620 -
Frontiers in Immunology 2020The thymus, a primary lymphoid organ, provides a complex environment essential for the generation of the T-cell repertoire. Thymic alterations occur during life either... (Review)
Review
The thymus, a primary lymphoid organ, provides a complex environment essential for the generation of the T-cell repertoire. Thymic alterations occur during life either in the context of thymic involution upon aging or the pathophysiological context of Myasthenia Gravis (MG). These changes involve complicated regulatory networks, in which microRNAs (miRNAs) are key players. Here, we analyzed the role of miRNAs in thymocyte maturation and differentiation sustained by thymic epithelial cells. We compared data from the literature regarding the role of mouse thymic miRNAs and original data obtained from a human thymic miRnome study. We identified a set of highly expressed miRNAs defined as ThymiRs and investigated miRNA expression in infants as compared to adults to determine those associated with human thymic involution. Thymic changes are also frequently observed in MG, an autoimmune disease which results in the production of anti-acetylcholine receptor (AChR) antibodies that lead to muscle weaknesses. Alterations such as thymoma in late-onset MG patients and hyperplasia with ectopic germinal centers (GCs) in early-onset (EOMG) patients are found. Thymic miRNA expression has been studied in AChR-MG patients both in thymoma-associated MG (TAMG) and EOMG, and their function through their mRNA targets investigated. Most of the dysregulated thymic miRNAs in EOMG are associated with GC development, such as miR-7, miR-24, miR-139, miR-143, miR-145, miR-146, miR-150, miR-452, miR-548 or thymic inflammation, such as miR-125b, miR-146, or miR-29. Understanding these pathways may provide therapeutic targets or biomarkers of disease manifestations.
Topics: Aging; Animals; Cell Differentiation; Epithelial Cells; Gene Expression Profiling; Humans; Mice; MicroRNAs; Myasthenia Gravis; T-Lymphocytes; Thymoma; Thymus Gland; Thymus Neoplasms
PubMed: 32587589
DOI: 10.3389/fimmu.2020.01074 -
Thoracic Cancer Nov 2019Thymic carcinomas (TCs) are rare aggressive tumors with no standard first-line treatment. This study was conducted to determine the optimal chemotherapy regimen for...
BACKGROUND
Thymic carcinomas (TCs) are rare aggressive tumors with no standard first-line treatment. This study was conducted to determine the optimal chemotherapy regimen for advanced TC.
METHODS
This retrospective study included 67 patients treated for stage IV TC in 2006-2015. The primary endpoints were the objective response rate (ORR) and progression-free survival (PFS) with different chemotherapy regimens. Multivariate Cox regression analysis was used to identify factors associated with PFS, including metastatic status, radiotherapy post-chemotherapy, primary lesion resection before chemotherapy, and chemotherapy regimen.
RESULTS
A total of 36 patients received a paclitaxel-platinum regimen, 31 received a gemcitabine-platinum regimen, 14 underwent primary lesion resection, and 33 underwent radiotherapy. ORR was 31% (11/36) and 29% (9/31) in the paclitaxel-platinum and gemcitabine-platinum groups, respectively (P = 0.890). Median PFS, one-year PFS rate, and two-year PFS rate were 7.0 months, 26%, and 6% with paclitaxel-platinum treatment and 12 months, 48%, and 24% with gemcitabine-platinum treatment (log-rank P = 0.030). Median PFS, one-year PFS rate, and two-year PFS rate were 18.0 months, 57%, and 33% with surgical resection and 7.3 months, 31%, and 7% without resection (log-rank P = 0.030). Median PFS, one-year PFS rate, and two-year PFS rate were 13.0 months, 52%, and 20% with radiotherapy and 4.3 months, 22%, and 7% without radiotherapy (log-rank P = 0.001). In multivariate analysis, metastatic status (hazard ratio [HR], 0.33, P = 0.004), surgical resection (HR, 0.32; P = 0.004), and radiotherapy (HR, 0.32; P < 0.001) were associated with superior PFS.
CONCLUSIONS
Both gemcitabine-platinum and paclitaxel-platinum regimens were efficacious for advanced TC. Primary lesion resection and radiotherapy may also benefit selected patients.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Combined Modality Therapy; Deoxycytidine; Female; Humans; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Paclitaxel; Retrospective Studies; Survival Analysis; Thymoma; Thymus Neoplasms; Treatment Outcome; Young Adult; Gemcitabine
PubMed: 31574576
DOI: 10.1111/1759-7714.13181 -
Virchows Archiv : An International... Jan 2021Thymomas exhibit a unique genomic landscape, comprising the lowest on average total mutational burden among adult human cancers; a unique point mutation in the GTF2I... (Review)
Review
Thymomas exhibit a unique genomic landscape, comprising the lowest on average total mutational burden among adult human cancers; a unique point mutation in the GTF2I gene in WHO type A and AB thymomas (and rarely others); almost unique KMT2A-MAML2 translocations in rare WHO type B2 and B3 thymomas; a unique YAP1-MAML2 translocation in almost all metaplastic thymomas; and unique miRNA profiles in relation to GTF2I mutational status and WHO histotypes. While most thymomas can be diagnosed solely on the basis of morphological features, mutational analyses can solve challenging differential diagnostic problems. No molecular biomarkers have been identified that predict the response of unresectable thymomas to chemotherapy or agents with known molecular targets. Despite the common and strong expression of PDL1 in thymomas, immune checkpoint inhibitors are rarely applicable due to the poor predictability of common, life-threatening autoimmune side effects that are related to the unrivaled propensity of thymomas towards autoimmunity.
Topics: Biomarkers, Tumor; DNA Mutational Analysis; Humans; Mutation; Pathology, Molecular; Thymoma; Thymus Neoplasms
PubMed: 33674910
DOI: 10.1007/s00428-021-03068-8 -
Scientific Reports Feb 2024B-cell subsets in peripheral blood (PB) and tumor microenvironment (TME) were evaluated to determine myasthenia gravis (MG) severity in patients with thymoma-associated...
B-cell subsets in peripheral blood (PB) and tumor microenvironment (TME) were evaluated to determine myasthenia gravis (MG) severity in patients with thymoma-associated MG (TMG) and the distribution of B cells in type B TMG. The distribution of mature B cells, including Bm1-Bm5, CD19 and CD20 B cells and non-switched (NSMBCs) and switched (SMBCs) memory B cells, were determined in 79 patients with thymoma or TMG. Quantitative relationships between the T and TMG groups and the TMG-low and TMG-high subgroups were determined. NSMBCs and SMBCs were compared in TME and PB. Type B thymoma was more likely to develop into MG, with types B2 and B3 being especially associated with MG worsening. The percentage of CD19 B cells in PB gradually increased, whereas the percentage of CD20 B cells and the CD19/CD20 ratio were not altered. The (Bm2 + Bm2')/(eBm5 + Bm5) index was significantly higher in the TMG-high than in thymoma group. The difference between SMBC/CD19 and NSMBC/CD19 B cell ratios was significantly lower in the thymoma than TMG group. NSMBCs assembled around tertiary lymphoid tissue in thymomas of patients with TMG. Few NSMBCs were observed in patients with thymoma alone, with these cells being diffusely distributed. MG severity in patients with TMG can be determined by measuring CD19 B cells and Bm1-Bm5 in PB. The CD19/CD20 ratio is a marker of disease severity in TMG patients. Differences between NSMBCs and SMBCs in PB and TME of thymomas can synergistically determine MG severity in patients with TMG.
Topics: Humans; Thymoma; B-Lymphocyte Subsets; Thymus Neoplasms; B-Lymphocytes; Myasthenia Gravis; Tumor Microenvironment
PubMed: 38302676
DOI: 10.1038/s41598-024-53250-6 -
The Journal of Thoracic and... Apr 2021
Topics: Humans; Neoplasm Staging; Thymoma; Thymus Neoplasms
PubMed: 33293061
DOI: 10.1016/j.jtcvs.2020.11.009