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Scientific Reports Jun 2024Cuproptosis is a newly defined form of programmed cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis...
Cuproptosis is a newly defined form of programmed cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis and metastasis. However, whether cuproptosis-related lncRNAs are involved in the pathogenesis of diffuse large B cell lymphoma (DLBCL) remains unclear. This study aimed to identify the prognostic signatures of cuproptosis-related lncRNAs in DLBCL and investigate their potential molecular functions. RNA-Seq data and clinical information for DLBCL were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Cuproptosis-related lncRNAs were screened out through Pearson correlation analysis. Utilizing univariate Cox, least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analysis, we identified seven cuproptosis-related lncRNAs and developed a risk prediction model to evaluate its prognostic value across multiple groups. GO and KEGG functional analyses, single-sample GSEA (ssGSEA), and the ESTIMATE algorithm were used to analyze the mechanisms and immune status between the different risk groups. Additionally, drug sensitivity analysis identified drugs with potential efficacy in DLBCL. Finally, the protein-protein interaction (PPI) network were constructed based on the weighted gene co-expression network analysis (WGCNA). We identified a set of seven cuproptosis-related lncRNAs including LINC00294, RNF139-AS1, LINC00654, WWC2-AS2, LINC00661, LINC01165 and LINC01398, based on which we constructed a risk model for DLBCL. The high-risk group was associated with shorter survival time than the low-risk group, and the signature-based risk score demonstrated superior prognostic ability for DLBCL patients compared to traditional clinical features. By analyzing the immune landscapes between two groups, we found that immunosuppressive cell types were significantly increased in high-risk DLBCL group. Moreover, functional enrichment analysis highlighted the association of differentially expressed genes with metabolic, inflammatory and immune-related pathways in DLBCL patients. We also found that the high-risk group showed more sensitivity to vinorelbine and pyrimethamine. A cuproptosis-related lncRNA signature was established to predict the prognosis and provide insights into potential therapeutic strategies for DLBCL patients.
Topics: Lymphoma, Large B-Cell, Diffuse; Humans; RNA, Long Noncoding; Prognosis; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Protein Interaction Maps; Male; Female; Gene Expression Profiling; Gene Regulatory Networks; Middle Aged
PubMed: 38839842
DOI: 10.1038/s41598-024-63433-w -
Cancer Reports (Hoboken, N.J.) Jun 2024Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Long noncoding RNA (lncRNA) is involved in many malignant tumors. This study...
BACKGROUND
Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide. Long noncoding RNA (lncRNA) is involved in many malignant tumors. This study aimed to clarify the role of the lncRNA plasmacytoma variant translocation 1 (PVT1) in CRC growth and metastasis.
METHODS
Differentially expressed lncRNAs in CRC were analyzed using the Cancer Genome Atlas. Gene expression profiling interactive analysis and a comprehensive resource for lncRNAs from cancer arrays databases were used to analyze lncRNA PVT1 expression and CRC prognosis, respectively. Cell counting kit-8, wound healing, colony formation, Transwell, and immunofluorescence assays were used to evaluate CRC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), respectively. Tumor growth and metastasis models were used to explore the PVT1 effect on the growth and metastasis of CRC in vivo.
RESULTS
PVT1 was highly expressed in CRC, associated with a poor prognosis of CRC, and showed good diagnostic value. Transfection of sh-PVT1 or pcDNA3.1-PVT1 reduced or increased the proliferation, wound healing rate, colony formation, invasion, and EMT of CRC cells. PVT1 and miR-3619-5p were co-expressed in CRC cytoplasm, and PVT1 acted as a competitive endogenous RNA (ceRNA) by sponging miR-3619-5p to up-regulate tripartite motif containing 29 (TRIM29) expression. MiR-3619-5p overexpression and TRIM29 knockdown reduced proliferation, wound healing rate, invasion, and EMT of CRC cells. However, simultaneous PVT1 and miR-3619-5p overexpression or knockdown of miR-3619-5p and TRIM29 knockdown rescued the malignant phenotype of CRC cells.
CONCLUSIONS
We first clarified the ceRNA mechanism of PVT1 in CRC, which induced growth and metastasis by sponging with miR-3619-5p to regulate TRIM29.
Topics: Humans; Colorectal Neoplasms; RNA, Long Noncoding; MicroRNAs; Cell Proliferation; Gene Expression Regulation, Neoplastic; Mice; Animals; Cell Movement; Prognosis; Epithelial-Mesenchymal Transition; Transcription Factors; Male; DNA-Binding Proteins; Mice, Nude; Female; Cell Line, Tumor; Neoplasm Metastasis; Mice, Inbred BALB C; Xenograft Model Antitumor Assays
PubMed: 38837682
DOI: 10.1002/cnr2.2085 -
Annals of Indian Academy of Neurology Apr 2024
PubMed: 38819414
DOI: 10.4103/aian.aian_28_24 -
Annals of Hematology May 2024Myeloma with extramedullary plasmacytomas not adjacent to bone (EMP) is associated with an extremely poor outcome compared with paraosseous plasmacytomas (PP) as current...
Daratumumab-based regimens for patients with multiple myeloma plus extramedullary plasmacytomas or paraskeletal plasmacytomas: initial follow-up of an Italian multicenter observational clinical experience.
Myeloma with extramedullary plasmacytomas not adjacent to bone (EMP) is associated with an extremely poor outcome compared with paraosseous plasmacytomas (PP) as current therapeutic approaches are unsatisfactory. The role of new molecules and in particular of monoclonal antibodies is under investigation. To determine whether daratumumab-based regimens are effective for myeloma with EMP, we report herein an initial multicenter observational analysis of 102 myeloma patients with EMP (n = 10) and PP (n = 25) at diagnosis and EMP (n = 28) and PP (n = 39) at relapse, treated with daratumumab-based regimens at 11 Haematological Centers in Italy.EMP and PP at diagnosis were associated with higher biochemical (90% vs. 96%, respectively) and instrumental ORR (86% vs. 83.3%, respectively), while at relapse, biochemical (74% vs. 73%) and instrumental (53% vs. 59%) ORR were lower. Median OS was inferior in EMP patients compared with patients with PP both at diagnosis (21.0 months vs. NR) (p = 0.005) and at relapse (32.0 vs. 40.0 months) (p = 0.428), although, during relapse, there was no statistically significant difference between the two groups. Surprisingly, at diagnosis, median TTP and median TTNT were not reached either in EMP patients or PP patients and during relapse there were no statistically significant differences in terms of median TTP (20 months for two groups), and median TTNT (24 months for PP patients vs. 22 months for EMP patients) between the two groups. Median TTR was 1 month in all populations.These promising results were documented even in the absence of local radiotherapy and in transplant-ineligible patients.
PubMed: 38805036
DOI: 10.1007/s00277-024-05811-y -
Cureus Apr 2024Extramedullary plasmacytomas without evidence of systemic illness make up less than 5% of all plasma cell neoplasms. The incidence of extramedullary plasmacytoma of the...
Extramedullary plasmacytomas without evidence of systemic illness make up less than 5% of all plasma cell neoplasms. The incidence of extramedullary plasmacytoma of the thyroid region is exceedingly rare. This report discusses the case of a 72-year-old male with extramedullary plasmacytoma of the thyroid. The patient underwent a total thyroidectomy for an enlarging right-sided thyroid nodule, and intraoperatively, the plasmacytoma was found to have an extracapsular component with adherence to the regional soft tissue as well as involvement of the right laryngeal nerve and regional lymph nodes. Despite a comprehensive negative workup for multiple myeloma initially, including a bone marrow biopsy and hematologic workup, the disease progressed to multiple myeloma following definitive radiation therapy, as evidenced by the development of hypermetabolic lytic lesions and further pathological examination. The patient's treatment course included systemic chemotherapy and an autologous stem cell transplant, resulting in a favorable treatment response. The progression to multiple myeloma despite established guidelines highlights the need for close observation and the potential for innovative therapeutic strategies to manage this rare entity.
PubMed: 38784303
DOI: 10.7759/cureus.58847 -
Journal of Mid-life Health 2024Individuals living with HIV face an elevated susceptibility to various plasma cell disorders, encompassing a spectrum that spans from benign conditions like plasma cell...
Individuals living with HIV face an elevated susceptibility to various plasma cell disorders, encompassing a spectrum that spans from benign conditions like plasma cell chronic inflammation to more severe conditions such as aggressive multiple myeloma. The present case is one of the few cases of plasma cell rich inflammation of the cervix, and is probably the first being reported in an HIV positive female. A 34-year-old female, P2L2 with last child birth 8 years back visited gynecology OPD with complaints of copious vaginal discharge from last 1 year. The discharge was yellowish in color, non-foul smelling, watery in consistency and present all through the menstrual cycle. On per speculum examination, the cervix looked unhealthy and bleeding on contact was present. The Pap Smear was suggestive of a high grade squamous intra-epithelial lesion (HSIL). Biopsy revealed intense plasma cell-rich inflammation in the subepithelial stroma with Russel bodies. A summary of all reported cases of Russel cell cervicitis, reported till date and key points to differentiate it from other plasma cell rich cervical lesions like malakoplakia and plasmacytoma are also presented.
PubMed: 38764927
DOI: 10.4103/jmh.jmh_255_23 -
Biomolecules & Biomedicine May 2024Hashimoto's thyroiditis (HT) is a prevalent autoimmune disease. We investigated the relationship of peripheral blood long noncoding RNA-plasmacytoma variant...
Hashimoto's thyroiditis (HT) is a prevalent autoimmune disease. We investigated the relationship of peripheral blood long noncoding RNA-plasmacytoma variant translocation 1 (lncRNA-PVT1) and microRNA (miR)-146a levels with Th17/Treg-related cytokines in HT patients and their clinical significance. Correlations of lncRNA-PVT1 and miR-146a with Th17/Treg-related cytokines were analyzed, and its clinical value in diagnosing HT was assessed. Results showed reduced lncRNA-PVT1 and interleukin (IL)-10 levels and increased miR-146a and IL-17 levels in HT patients. lncRNA-PVT1 negatively interrelated with miR-146a, IL-17, IL-23 and IL-6, and positively interrelated with IL-10; miR-146a positively correlated with IL-17, IL-23 and IL-6, but negatively correlated with IL-10 in HT patients. The area under the curve (AUC) of lncRNA-PVT1 and miR-146a levels for diagnosing HT were 0.822 and 0.844, respectively (sensitivity 88.73% and 86.62%, specificity 67.02% and 69.15%, cut-off values 0.76 and 2.73), with their combined detections yielding a higher AUC. Patients with poorly expressed lncRNA-PVT1 and highly expressed miR-146a had elevated HT incidence. lncRNA-PVT1 and miR-146a levels were also found to be an independent influencing factor for HT occurrence. Our findings suggest that HT patients have low peripheral blood lncRNA-PVT1 expression and high miR-146a expression. lncRNA-PVT1 and miR-146a level changes were correlated with Th17/Treg cytokine imbalance and could be a potential diagnostic tool and independent influencing factor for HT.
PubMed: 38761409
DOI: 10.17305/bb.2024.10237 -
Journal of Experimental & Clinical... May 2024Sorafenib is a standard first-line treatment for advanced hepatocellular carcinoma (HCC), yet its effectiveness is often constrained. Emerging studies reveal that...
BACKGROUND
Sorafenib is a standard first-line treatment for advanced hepatocellular carcinoma (HCC), yet its effectiveness is often constrained. Emerging studies reveal that sorafenib triggers ferroptosis, an iron-dependent regulated cell death (RCD) mechanism characterized by lipid peroxidation. Our findings isolate the principal target responsible for ferroptosis in HCC cells and outline an approach to potentially augment sorafenib's therapeutic impact on HCC.
METHODS
We investigated the gene expression alterations following sgRNA-mediated knockdown induced by erastin and sorafenib in HCC cells using CRISPR screening-based bioinformatics analysis. Gene set enrichment analysis (GSEA) and the "GDCRNATools" package facilitated the correlation studies. We employed tissue microarrays and cDNA microarrays for validation. Ubiquitination assay, Chromatin immunoprecipitation (ChIP) assay, RNA immunoprecipitation (RIP) assay, and dual-luciferase reporter assay were utilized to delineate the specific mechanisms underlying ferroptosis in HCC cells.
RESULTS
Our study has revealed that pleiomorphic adenoma gene 1 (PLAG1), a gene implicated in pleomorphic adenoma, confers resistance to ferroptosis in HCC cells treated with sorafenib. Sorafenib leads to the opposite trend of protein and mRNA levels of PLAG1, which is not caused by affecting the stability or ubiquitination of PLAG1 protein, but by the regulation of PLAG1 at the transcriptional level by its upstream competitive endogenous long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1). Data from 139 HCC patients showed a significant positive correlation between PLAG1 and GPX4 levels in tumor samples, and PLAG1 is instrumental in redox homeostasis by driving the expression of glutathione peroxidase 4 (GPX4), the enzyme that reduces lipid peroxides (LPOs), which further leads to ferroptosis inhibition.
CONCLUSIONS
Ferroptosis is a promising target for cancer therapy, especially for patients resistant to standard chemotherapy or immunotherapy. Our findings indicate that PLAG1 holds therapeutic promise and may enhance the efficacy of sorafenib in treating HCC.
Topics: Humans; Sorafenib; Ferroptosis; Carcinoma, Hepatocellular; Liver Neoplasms; Phospholipid Hydroperoxide Glutathione Peroxidase; DNA-Binding Proteins; MicroRNAs; Mice; Animals; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Male
PubMed: 38745179
DOI: 10.1186/s13046-024-03061-4 -
Journal of Neurosurgery. Case Lessons May 2024Plasmacytoma, a rare plasma cell disorder, often presents as a solitary or multiple tumors within the bone marrow or soft tissues, typically associated with multiple...
BACKGROUND
Plasmacytoma, a rare plasma cell disorder, often presents as a solitary or multiple tumors within the bone marrow or soft tissues, typically associated with multiple myeloma. Extramedullary plasmacytomas (EMPs), particularly those located in the external auditory canal (EAC), are exceedingly rare and pose significant treatment challenges given their location, anatomical complexity, and high risk of recurrence.
OBSERVATIONS
The authors report the case of a 72-year-old male with a history of multiple myeloma, presenting with recurrent left EAC plasmacytoma. After initial conventional radiotherapy for the lesion, a recurrence was documented in 7 years. The patient subsequently underwent stereotactic radiosurgery, which proved successful, leading to complete resolution of the lesion without any long-term adverse effects or radiation-related complications over a 45-month period.
LESSONS
This case is a unique instance of utilizing stereotactic radiosurgery for recurrent EMP in the EAC, highlighting its potential as an effective approach in managing complex plasmacytomas.
PubMed: 38710109
DOI: 10.3171/CASE2479 -
Leukemia Research Reports 2024Orbital plasmacytoma is rare and has only been reported in the context of the initial diagnosis of multiple myeloma. Moreover, isolated orbital plasmacytoma without any...
Orbital plasmacytoma is rare and has only been reported in the context of the initial diagnosis of multiple myeloma. Moreover, isolated orbital plasmacytoma without any signs of multiple myeloma is extremely rare. We report the case of a 59-year-old female patient diagnosed with IgA Kappa multiple myeloma. It was stage I ISS (International Staging System) and stage I R-ISS (Revised ISS). According to the Tunisian national protocol, the patient was included in the standard-risk group and was eligible for four cycles of CTD (Cyclophosphamide, Thalidomide, Dexamethasone) followed by autologous stem cell transplantation. Taking into account the partial response after the CTD cycles, the patient has benefited from two VTD cycles (Bortezomib, Thalidomide, Dexamethasone). Thus, complete remission was obtained. The patient refused autologous stem cell transplantation. Therefore, maintenance treatment based on Thalidomide only was started and received over a twelve-month period. Five months after the end of maintenance treatment, she reported frontal headaches that were resistant to symptomatic treatment, with ptosis in the right eye in physical examination. Brain MRI revealed the presence of a right cranio-orbital tissue mass with intra-orbital and extra-axial cerebral components. The mass measured 32/36 mm on axial sections and 47 mm in height. The patient underwent a complete resection of the cranio-orbital mass with cranioplasty. The histopathological examination of the mass with Immunohistochemistry staining confirmed the diagnosis of orbital plasmocytoma. An update of the multiple myeloma assessment did not reveal any biological, cytological or radiological signs in favor of multiple myeloma. Therefore the diagnosis of isolated orbital plasmacytoma without signs of multiple myeloma was made. Post-operative brain MRI showed complete disappearance of the right cranio-orbital tissue lesion. There was only a persistent meningeal enhancement of the dura mater at the surgical site, suggestive of post-operative changes. The patient was then referred for cranio-orbital radiotherapy.
PubMed: 38707773
DOI: 10.1016/j.lrr.2024.100460