Molecular profiling of thymoma with myasthenia gravis: Risk factors of developing myasthenia gravis in thymoma patients

Lee, Ming-Ching; Hsiao, Tzu‐Hung; Chuang, Han‐Ni; Lee, Li-Wen; Ling, Pei-Ra; Tsai, Hui-Mei; Mao, Chien-Lin; Hsu, Chung-Ping

doi:10.1016/j.lungcan.2019.11.007

Cited by 11 publications

(10 citation statements)

References 53 publications

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“…At present, the medical community has not found the specific pathogenesis of MG and has presumed that it may be associated with infection factors, environmental factors, etc. [12][13][14]. Immunosuppressants combined with GCS is effective for some MG patients, except for a minority of patients.…”

Section: Discussionmentioning

confidence: 99%

[Retracted] Analysis on the Clinical Effect of High‐Dose Glucocorticoids Combined with Immunosuppressants on Patients with Myasthenia Gravis Undergoing Video‐Assisted Thoracoscopic Surgery

Liu

Wang

et al. 2021

BioMed Research International

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Objective. The purpose of the study was to investigate the clinical effect of high-dose glucocorticoids (GCS) combined with immunosuppressants on the treatment of myasthenia gravis (MG) with video-assisted thoracoscopic surgery (VATS). Methods. A total of 106 MG patients admitted to the neurology department of our hospital from February 2016 to February 2020 were selected as the study subjects and divided into experimental group ( n = 53 ) and control group ( n = 53 ). The patients in the control group underwent VATS, while the patients in the experimental group were treated with high-dose GCS combined with immunosuppressants on the basis of VATS treatment. The clinical efficacy of different MG treatment methods was analyzed. Results. No significant differences were observed in visual analogue score (VAS) at T1 between the two groups ( P > 0.05 ), while VAS scores at T2, T3, and T4 in the experimental group were significantly lower than those in the control group ( P < 0.001 ). In the experimental group, the overall response rate was significantly higher than the control group ( P < 0.05 ). Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) level in regulatory T (Treg) cells in experimental groups after treatment was significantly higher, compared to that in before treatment and the control group ( P < 0.05 ). Similar results of each quantitative MG score were displayed in both groups after treatment, compared to before treatment and the control group ( P < 0.05 ). Clinical performance of patients with lower incidence of adverse reactions in the experimental groups after treatment was significantly higher than those in the control group ( P < 0.001 ). Conclusion. GCS combined with immunosuppressants can effectively relieve patients’ clinical symptoms and improve their quality of life, with significant clinical efficacy and high safety, which is worthy of application and promotion.

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Section: Discussionmentioning

confidence: 99%

[Retracted] Analysis on the Clinical Effect of High‐Dose Glucocorticoids Combined with Immunosuppressants on Patients with Myasthenia Gravis Undergoing Video‐Assisted Thoracoscopic Surgery

Liu

Wang

et al. 2021

BioMed Research International

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“…Similarly, a differential expression analysis of 34 Tms with or without MG (N = 16 and N = 18, respectively) identified 140 differentially expressed genes [32]. In particular, insulin-like growth factor-binding protein (IGFBP1), Krüppel-like factor 15 (KLF15) transcription factor, pyruvate dehydrogenase kinase (PDK4) and hypoxia-inducible factor (HIF3A) were more expressed in Tm associated with MG than in those not associated with it, thus suggesting a role for these genes expression, especially HIF3A and IGBP1, in the pathogenesis of MG [32].…”

Section: Immunopathology Of Tetsmentioning

confidence: 99%

“…In particular, the medium-sized neurofilament (NEFM), whose protein product exhibits immunogenic similarities with the AChR α-subunit and titin, is mainly overexpressed in MG+ A/AB Tms, while the neuronal RYR3, whose encoded protein shares homology with muscular RYR1 and cardiac RYR2, is predominantly overexpressed in MG+ B Tms [16]. Similarly, a differential expression analysis of 34 Tms with or without MG (N = 16 and N = 18, respectively) identified 140 differentially expressed genes [32]. In particular, insulin-like growth factor-binding protein (IGFBP1), Krüppel-like factor 15 (KLF15) transcription factor, pyruvate dehydrogenase kinase (PDK4) and hypoxia-inducible factor (HIF3A) were more expressed in Tm associated with MG than in those not associated with it, thus suggesting a role for these genes expression, especially HIF3A and IGBP1, in the pathogenesis of MG [32].…”

Section: Immunopathology Of Tetsmentioning

confidence: 99%

Immunobiology of Thymic Epithelial Tumors: Implications for Immunotherapy with Immune Checkpoint Inhibitors

Tateo

Manuzzi

Giglio

et al. 2020

IJMS

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Thymic epithelial tumors (TETs) are a group of rare thoracic malignancies, including thymic carcinomas (TC) and thymomas (Tm). Autoimmune paraneoplastic diseases are often observed in TETs, especially Tms. To date, chemotherapy is still the standard treatment for advanced disease. Unfortunately, few therapeutic options are available for relapsed/refractory TETs. In the last few years, the deepening of knowledge on thymus’ immunobiology and involved altered genetic pathways have laid the foundation for new treatment options in these rare neoplasms. Recently, the immunotherapy revolution has landed in TETs, showing both a dark and light side. Indeed, despite the survival benefit, the occurrence of severe autoimmune treatment-related adverse events has risen crescent uncertainty about the feasibility of immunotherapy in these patients, prone to autoimmunity for their cancer biology. In this review, after summarizing immunobiology and immunopathology of TETs, we discuss available data on immune-checkpoint inhibitors and future perspectives of this therapeutic strategy.

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“…Some other molecular features have been further described for patients not reporting TRMG, such as upregulated TGF-β and WNT pathways (56), nonetheless those routes hardly respond to immunotherapy. Finally, several other biomarkers have been evaluated to differentiate thymomas from TCs (55,59) and to understand the pathogenesis of MG such as IGFBP1, KLF15, PDK4 and, HIF3A (60). Indeed, other AIDs such as encephalitis or polymyositis has been correlated with the enhance of anti-Hu antibodies, Ma2 antibodies and CRP5 antibodies (61) or deregulation of T-cell-receptor (TCR) and upregulated MHC-I expression on muscle fibers (62); but MG and AID landscape is still unknown.…”

Section: Molecular Features Of Aids and Tetsmentioning

confidence: 99%

Narrative review of immunotherapy in thymic malignancies

Benítez¹,

Besse²

2021

Transl Lung Cancer Res

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Thymomas and thymic carcinomas (TCs) (also known as Thymic Epithelial Tumors or TETs) are rare cancers and the most frequent masses of the anterior mediastinum. These tumors appear in the epithelial component of the thymus, a primary lymphoid organ, and they have reported a high risk of autoimmunity due to a unique biology. Indeed, up to 30% of patients with TETs could present an autoimmune disorder (AID), the most frequent being Myasthenia Gravis (MG). Moreover, AIDs have been reported not only at tumor diagnosis but before and during the follow-up. These tumors have a lack of specific therapeutic targets for metastatic setting. Immune checkpoint inhibitors (ICI) may defeat cancer cells' capacity to evade the immune system and proliferate. The long-term benefit of ICIs in the metastatic setting in several tumors, such as melanoma or non-small cell lung cancer (NSCLC), let to evaluate ICI approaches in TETs.The high rate of AIDs and distribution of autoimmune events among TET's histological subtypes may have an influence on the decision regarding a treatment based on ICI due to the increased risk of toxicity. We summarize the current evidence for the efficacy of ICI in thymoma and TC and discuss several unresolved challenges and concerns for the use of this agents in TETs.

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Molecular profiling of thymoma with myasthenia gravis: Risk factors of developing myasthenia gravis in thymoma patients

Cited by 11 publications

References 53 publications

[Retracted] Analysis on the Clinical Effect of High‐Dose Glucocorticoids Combined with Immunosuppressants on Patients with Myasthenia Gravis Undergoing Video‐Assisted Thoracoscopic Surgery

[Retracted] Analysis on the Clinical Effect of High‐Dose Glucocorticoids Combined with Immunosuppressants on Patients with Myasthenia Gravis Undergoing Video‐Assisted Thoracoscopic Surgery

Immunobiology of Thymic Epithelial Tumors: Implications for Immunotherapy with Immune Checkpoint Inhibitors

Narrative review of immunotherapy in thymic malignancies

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