RESUMO
The prognostication of survival trajectories in multiple myeloma (MM) patients presents a substantial clinical challenge. Leveraging transcriptomic and clinical profiles from an expansive cohort of 2,088 MM patients, sourced from the Gene Expression Omnibus and The Cancer Genome Atlas repositories, we applied a sophisticated nested lasso regression technique to construct a prognostic model predicated on 28 gene pairings intrinsic to cell death pathways, thereby deriving a quantifiable risk stratification metric. Employing a threshold of 0.15, we dichotomized the MM samples into discrete high-risk and low-risk categories. Notably, the delineated high-risk cohort exhibited a statistically significant diminution in survival duration, a finding which consistently replicated across both training and external validation datasets. The prognostic acumen of our cell death signature was further corroborated by TIME ROC analyses, with the model demonstrating robust performance, evidenced by AUC metrics consistently surpassing the 0.6 benchmark across the evaluated arrays. Further analytical rigor was applied through multivariate COX regression analyses, which ratified the cell death risk model as an independent prognostic determinant. In an innovative stratagem, we amalgamated this risk stratification with the established International Staging System (ISS), culminating in the genesis of a novel, refined ISS categorization. This tripartite classification system was subjected to comparative analysis against extant prognostic models, whereupon it manifested superior predictive precision, as reflected by an elevated C-index. In summation, our endeavors have yielded a clinically viable gene pairing model predicated on cellular mortality, which, when synthesized with the ISS, engenders an augmented prognostic tool that exhibits pronounced predictive prowess in the context of multiple myeloma.
Assuntos
Morte Celular , Mieloma Múltiplo , Mieloma Múltiplo/patologia , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Humanos , Prognóstico , Masculino , Feminino , Medição de Risco , Perfilação da Expressão Gênica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Idoso , Análise de SobrevidaRESUMO
Immune thrombocytopenia (ITP) is an autoimmune disease caused by T-cell dysfunction. Recently, several studies have shown that a disturbed Th17/Treg balance contributes to the development of ITP. MicroRNAs (miRNAs) are small noncoding RNA moleculesthat posttranscriptionally regulate gene expression. Emerging evidences have demonstrated that miRNAs play an important role in regulating the Th17/Treg balance. In the present study, we found that miR-641 was upregulated in ITP patients. In primary T cells, overexpression of miR-641 could cause downregulation of its target genes STIM1 and SATB1, thus inducing a Th17 (upregulated)/Treg (downregulated) imbalance. Inhibition of miR-641 by a miR-641 sponge in primary T cells of ITP patients or by antagomiR-641 in an ITP murine model could cause upregulation of STIM1 and SATB1, thus restoring Th17/Treg homeostasis. These results suggested that the miR-641-STIM/SATB1 axis plays an important role in regulating the Th17/Treg balance in ITP.
Assuntos
Proteínas de Ligação à Região de Interação com a Matriz , MicroRNAs , Púrpura Trombocitopênica Idiopática , Molécula 1 de Interação Estromal , Linfócitos T Reguladores , Células Th17 , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Animais de Doenças , Regulação da Expressão Gênica , Proteínas de Ligação à Região de Interação com a Matriz/genética , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/metabolismo , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismoRESUMO
Small B-cell lymphoma is the classification of B-cell chronic lymphoproliferative disorders that include chronic lymphocytic leukaemia/small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia. The clinical presentation is somewhat heterogeneous, and its occurrence and development mechanisms are not yet precise and may involve epigenetic changes. Epigenetic alterations mainly include DNA methylation, histone modification, and non-coding RNA, which are essential for genetic detection, early diagnosis, and assessment of treatment resistance in small B-cell lymphoma. As chronic lymphocytic leukemia/small lymphocytic lymphoma has already been reported in the literature, this article focuses on small B-cell lymphomas such as follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma, and Waldenstrom macroglobulinemia. It discusses recent developments in epigenetic research to diagnose and treat this group of lymphomas. This review provides new ideas for the treatment and prognosis assessment of small B-cell lymphoma by exploring the connection between small B-cell lymphoma and epigenetics. (AU)