cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.28295445.v1
title: Prognostic signature based on mitochondria- and angiogenesis-related genes associated with immune microenvironment of multiple myeloma

description: Mitochondria and angiogenesis play key roles in multiple myeloma (MM) development, but their interrelated genes affecting MM prognosis are under-studied. We analyzed TCGA_MMRF and GSE4581 datasets to identify four genes – CCNB1, CDC25C, HSP90AA1, and PARP1 – that significantly correlate with MM prognosis, with high expression indicating poor outcomes. A prognostic signature based on these genes stratified patients into high- and low-risk groups, with the latter showing better survival. The signature was validated as an independent prognostic factor. Biological function analysis revealed differences in cell cycle processes between risk groups, and immune microenvironment analysis showed distinct immune cell infiltration patterns. This mitochondria- and angiogenesis-related prognostic signature could enhance MM prognosis assessment and offer new therapeutic insights.
DOI: 10.6084/m9.figshare.29041185
title: Pan-cancer analysis reveals PRRT4 is a potential prognostic factor of AML

description: Proline-rich transmembrane protein 4 (PRRT4) has been infrequently studied, with limited literature suggesting its potential as a prognostic marker for gastric cancer. This study aims to investigate the prognostic value of the PRRT4 gene in pan-cancer. We acquired and analyzed data from several platforms, including The Cancer Genome Atlas (TCGA), Genotype Tissue Expression Project (GTEx), Cancer Cell Line Encyclopedia (CCLE), cBioPortal, HPA, and TIMER 2.0. In addition, we have further analyzed the data using multivariate analyzes and RT-qPCR. In vitro experiments were performed to detect the proliferation and apoptosis of AML cells before and after PRRT4 knockdown. PRRT4 exhibited low expression in 10 types of cancers and high expression in 3 types, and this expression was significantly correlated with tumor stage, age, and gender across various cancer types. PRRT4, identified as a potential independent prognostic factor for overall survival (OS) in several cancers including LAML, PAAD, SKCM, STAD, THYM, and UVM, and exhibited a high frequency of mutation in UCEC. Moreover, PRRT4 was found to be correlated with DNA methylation and immune infiltration in various cancers. Ultimately, in the multivariate analysis model, PRRT4 was discerned as an independent prognostic biomarker for AML, predicated on the statistics based from our institution. After PRRT4 knockdown, the proliferation ability of THP1 cells was significantly enhanced, and the apoptosis ratio was significantly decreased. PRRT4 may serve as a potential therapeutic target and prognostic marker for various malignancies. This study comprehensively analyzed the expression of PRRT4 in 33 cancers through data from multiple databases, and further analyzed the relationship between PRRT4 expression and patients' clinical characteristics, prognosis, gene mutation, immune status, TMB, MSI, and DNA methylation. Results suggest that PRRT4 is a potential independent prognostic predictor for a variety of cancers, including LAML, PAAD, SKCM, STAD, THYM, and UVM. Based on this, we examined the expression of PRRT4 in our previously included leukemia clinical samples, and the results of univariate and multivariate analysis showed that PRRT4 was an independent prognostic factor in leukemia patients. After PRRT4 knockdown, the proliferation ability of THP1 cells was significantly enhanced, and the apoptosis ratio was significantly decreased.
DOI: 10.6084/m9.figshare.29041185.v1
title: Pan-cancer analysis reveals PRRT4 is a potential prognostic factor of AML

description: Proline-rich transmembrane protein 4 (PRRT4) has been infrequently studied, with limited literature suggesting its potential as a prognostic marker for gastric cancer. This study aims to investigate the prognostic value of the PRRT4 gene in pan-cancer. We acquired and analyzed data from several platforms, including The Cancer Genome Atlas (TCGA), Genotype Tissue Expression Project (GTEx), Cancer Cell Line Encyclopedia (CCLE), cBioPortal, HPA, and TIMER 2.0. In addition, we have further analyzed the data using multivariate analyzes and RT-qPCR. In vitro experiments were performed to detect the proliferation and apoptosis of AML cells before and after PRRT4 knockdown. PRRT4 exhibited low expression in 10 types of cancers and high expression in 3 types, and this expression was significantly correlated with tumor stage, age, and gender across various cancer types. PRRT4, identified as a potential independent prognostic factor for overall survival (OS) in several cancers including LAML, PAAD, SKCM, STAD, THYM, and UVM, and exhibited a high frequency of mutation in UCEC. Moreover, PRRT4 was found to be correlated with DNA methylation and immune infiltration in various cancers. Ultimately, in the multivariate analysis model, PRRT4 was discerned as an independent prognostic biomarker for AML, predicated on the statistics based from our institution. After PRRT4 knockdown, the proliferation ability of THP1 cells was significantly enhanced, and the apoptosis ratio was significantly decreased. PRRT4 may serve as a potential therapeutic target and prognostic marker for various malignancies. This study comprehensively analyzed the expression of PRRT4 in 33 cancers through data from multiple databases, and further analyzed the relationship between PRRT4 expression and patients' clinical characteristics, prognosis, gene mutation, immune status, TMB, MSI, and DNA methylation. Results suggest that PRRT4 is a potential independent prognostic predictor for a variety of cancers, including LAML, PAAD, SKCM, STAD, THYM, and UVM. Based on this, we examined the expression of PRRT4 in our previously included leukemia clinical samples, and the results of univariate and multivariate analysis showed that PRRT4 was an independent prognostic factor in leukemia patients. After PRRT4 knockdown, the proliferation ability of THP1 cells was significantly enhanced, and the apoptosis ratio was significantly decreased.
DOI: 10.6084/m9.figshare.29041530
title: Gene prediction of the relationship between iron deficiency anemia and immune cells

description: Observational studies have shown a potential link between immune factors and the risk of iron deficiency anemia (IDA), yet the causal relationship between immune cells and IDA remains enigmatic. Herein, we used Mendelian randomization (MR) to assess whether this association is causal. We selected IDA genetic variants, including 8376 samples and 9810691 single nucleotide polymorphisms, and immune cells from a large open genome-wide association study (GWAS) for a bidirectional MR study. The primary method was inverse variance weighting (IVW), and auxiliary analyses were MR-Egger, weighted median, simple mode and weighted mode. The reliability of the results was subsequently verified by heterogeneity and sensitivity analysis. IVW method showed that 19 types of immune cells may be the risk factors of IDA, whereas 15 types of immune cells are the protective factors of IDA. Reverse MR analysis suggested that immune cells from upstream etiology of IDA are not involved in follow-up immune activities. Next, we selected 731 immune cell types as the results. The research revealed that IDA may result in a rise in 23 kinds of immune cells and a reduction in 12 kinds of immune cells. In addition, sensitivity analysis demonstrated no evidence of heterogeneity or horizontal pleiotropy. From a genetic standpoint, our study suggests that specific immune cells may be involved in the occurrence of IDA. Inversely, IDA may also contribute to immune dysfunction, thus guiding future clinical investigations.
DOI: 10.6084/m9.figshare.29041530.v1
title: Gene prediction of the relationship between iron deficiency anemia and immune cells

description: Observational studies have shown a potential link between immune factors and the risk of iron deficiency anemia (IDA), yet the causal relationship between immune cells and IDA remains enigmatic. Herein, we used Mendelian randomization (MR) to assess whether this association is causal. We selected IDA genetic variants, including 8376 samples and 9810691 single nucleotide polymorphisms, and immune cells from a large open genome-wide association study (GWAS) for a bidirectional MR study. The primary method was inverse variance weighting (IVW), and auxiliary analyses were MR-Egger, weighted median, simple mode and weighted mode. The reliability of the results was subsequently verified by heterogeneity and sensitivity analysis. IVW method showed that 19 types of immune cells may be the risk factors of IDA, whereas 15 types of immune cells are the protective factors of IDA. Reverse MR analysis suggested that immune cells from upstream etiology of IDA are not involved in follow-up immune activities. Next, we selected 731 immune cell types as the results. The research revealed that IDA may result in a rise in 23 kinds of immune cells and a reduction in 12 kinds of immune cells. In addition, sensitivity analysis demonstrated no evidence of heterogeneity or horizontal pleiotropy. From a genetic standpoint, our study suggests that specific immune cells may be involved in the occurrence of IDA. Inversely, IDA may also contribute to immune dysfunction, thus guiding future clinical investigations.
DOI: 10.6084/m9.figshare.30742456
title: <i>TMEM91::TAL1</i> Fusion gene in a middle-aged female with rapid MDS to secondary AML progression: a case report

description: <i>TMEM91::TAL1</i> fusion has been identified in glioblastoma but has never been documented in hematologic malignancies. We document the first presentation of the <i>TMEM91::TAL1</i> fusion in a myelodysplastic syndrome (MDS) with rapid transition into secondary acute myeloid leukemia (sAML). A middle-aged female presented to the hematology clinic complaining primarily of fatigue and a workup revealing pancytopenia. Bone marrow (BM) biopsy demonstrated 8% blasts with myelodysplastic changes and secondary myelofibrosis. RNA sequencing detected the <i>TMEM91::TAL1</i> fusion at 1.79% in the presence of normal cytogenetics and a minimal inhibitory <i>DNMT3A</i> mutation (1.3%). Despite multiple cycles of azacitidine, within one month, the patient had transitioned into sAML with blasts increased to 55% with heterogeneity in the sample, and <i>TMEM91::TAL1</i> expression increased to 2.83%. The patient underwent haploidentical stem cell transplantation with complete remission and no evidence of <i>TMEM91::TAL1</i> fusion. The <i>TMEM91::TAL1</i> fusion (resulting from a breakpoint at exon 3 of <i>TMEM91</i> and exon 5 of <i>TAL1</i>) was detected by RNA-seq while not detected by whole genome sequencing. The expression of <i>TMEM91::TAL1</i> fusion increased with the progression from MDS to sAML and was eliminated after HSCT. This case illustrates the value of comprehensive molecular profiling, including RNA-seq, in cases of rapidly progressive MDS that cannot be diagnosed through standard molecular diagnostics. The temporal relationship between expression of the fusions and disease progression warrants additional studies of <i>TMEM91::TAL1</i> in myeloid malignancies.
DOI: 10.6084/m9.figshare.30742456.v1
title: <i>TMEM91::TAL1</i> Fusion gene in a middle-aged female with rapid MDS to secondary AML progression: a case report

description: <i>TMEM91::TAL1</i> fusion has been identified in glioblastoma but has never been documented in hematologic malignancies. We document the first presentation of the <i>TMEM91::TAL1</i> fusion in a myelodysplastic syndrome (MDS) with rapid transition into secondary acute myeloid leukemia (sAML). A middle-aged female presented to the hematology clinic complaining primarily of fatigue and a workup revealing pancytopenia. Bone marrow (BM) biopsy demonstrated 8% blasts with myelodysplastic changes and secondary myelofibrosis. RNA sequencing detected the <i>TMEM91::TAL1</i> fusion at 1.79% in the presence of normal cytogenetics and a minimal inhibitory <i>DNMT3A</i> mutation (1.3%). Despite multiple cycles of azacitidine, within one month, the patient had transitioned into sAML with blasts increased to 55% with heterogeneity in the sample, and <i>TMEM91::TAL1</i> expression increased to 2.83%. The patient underwent haploidentical stem cell transplantation with complete remission and no evidence of <i>TMEM91::TAL1</i> fusion. The <i>TMEM91::TAL1</i> fusion (resulting from a breakpoint at exon 3 of <i>TMEM91</i> and exon 5 of <i>TAL1</i>) was detected by RNA-seq while not detected by whole genome sequencing. The expression of <i>TMEM91::TAL1</i> fusion increased with the progression from MDS to sAML and was eliminated after HSCT. This case illustrates the value of comprehensive molecular profiling, including RNA-seq, in cases of rapidly progressive MDS that cannot be diagnosed through standard molecular diagnostics. The temporal relationship between expression of the fusions and disease progression warrants additional studies of <i>TMEM91::TAL1</i> in myeloid malignancies.
DOI: 10.6084/m9.figshare.29712150
title: Exploring potential causal effects of circulating inflammatory proteins on hematologic malignancies and identifying cross-cancer drug targets: a Mendelian randomization study

description: Although a substantial body of research has underscored the pivotal role of inflammatory proteins in hematologic malignancies, precise understanding of the underlying mechanisms is limited. Therefore, it’s necessary to explore the possible causal relationships between specific circulating inflammatory proteins and these malignancies by using a genome-wide association approach. To evaluate the possible causal effects, we performed a two-sample Mendelian randomization (MR) study. Summary statistics for 91 proteins, sourced from large-scale genome-wide association studies, were integrated with data on 11 hematologic malignancies from the FinnGen consortium. Inverse variance weighting was applied as the primary method for MR analysis, with detailed sensitivity analyses conducted to ensure robustness. Furthermore, protein–protein interaction analysis and cross-cancer effect assessments were performed to identify potential common drug targets. Our analysis demonstrated both positive and negative associations of circulating inflammatory proteins on the development of 11 hematologic malignancies. Nine proteins exhibited cross-cancer effects. MCP-1, CXCL8, IL-1α, and SCF were associated with an increased risk of hematologic malignancies, while IFN-γ, IL-10, CD40, SULT1A1, and CXCL5 were associated with a reduced risk. The results of the study provided possible causal evidence for the involvement of circulating inflammatory proteins in the pathogenesis of eleven hematologic malignancies. Nine proteins with cross-cancer effects were of special interest, and their potential as targets in the therapeutic intervention of blood malignancies was highlighted.
DOI: 10.6084/m9.figshare.29712150.v1
title: Exploring potential causal effects of circulating inflammatory proteins on hematologic malignancies and identifying cross-cancer drug targets: a Mendelian randomization study

description: Although a substantial body of research has underscored the pivotal role of inflammatory proteins in hematologic malignancies, precise understanding of the underlying mechanisms is limited. Therefore, it’s necessary to explore the possible causal relationships between specific circulating inflammatory proteins and these malignancies by using a genome-wide association approach. To evaluate the possible causal effects, we performed a two-sample Mendelian randomization (MR) study. Summary statistics for 91 proteins, sourced from large-scale genome-wide association studies, were integrated with data on 11 hematologic malignancies from the FinnGen consortium. Inverse variance weighting was applied as the primary method for MR analysis, with detailed sensitivity analyses conducted to ensure robustness. Furthermore, protein–protein interaction analysis and cross-cancer effect assessments were performed to identify potential common drug targets. Our analysis demonstrated both positive and negative associations of circulating inflammatory proteins on the development of 11 hematologic malignancies. Nine proteins exhibited cross-cancer effects. MCP-1, CXCL8, IL-1α, and SCF were associated with an increased risk of hematologic malignancies, while IFN-γ, IL-10, CD40, SULT1A1, and CXCL5 were associated with a reduced risk. The results of the study provided possible causal evidence for the involvement of circulating inflammatory proteins in the pathogenesis of eleven hematologic malignancies. Nine proteins with cross-cancer effects were of special interest, and their potential as targets in the therapeutic intervention of blood malignancies was highlighted.
DOI: 10.6084/m9.figshare.30445797
title: NPM1 mediated up – regulation of CXCR4 might drive bortezomib resistance in multiple Myeloma

description: Bortezomib (BTZ) containing regimens induces significant antitumor response in multiple myeloma (MM) and are considered as the first-line treatment. However, resistance is still one of the unsolved problems. This study aims to explore the mechanism underlying BTZ resistance in MM. The gene expression profile (GEP) data of the GEO dataset GSE9782 was analyzed. All cases were divided into BTZ sensitive and resistant arms. Differentially expressed genes (DEGs) and later the hub genes between the two groups were screened. The key hub gene NPM1 was inhibited by shRNA and small molecule inhibitor, proliferation, apoptosis and expression of CXCR4 in myeloma cells were assayed. NPM1 was a dismal survival prognostic factor in MM, and MM patients with high NPM1 expression achieved significantly lower response rate to BTZ-containing regimens. In vitro, qRT-PCR revealed that NPM1 expression in the BTZ-resistant MM cell line KM3/BTZ (also known as KB) was significantly higher than its parental cell line KM3 cells. Knockdown of NPM1 and treatment with the NPM1 inhibitor NSC348884 both restored the sensitivity of KB cells to BTZ. Further analysis revealed that inhibition of NPM1 down-regulated CXCR4 expression at both transcriptional and translational level. In conclusion, NPM1 might causes BTZ resistance via up-regulating CXCR4 expression in MM and could be served as both a new prognostic biomarker and a promising therapeutic target.
DOI: 10.6084/m9.figshare.30445797.v1
title: NPM1 mediated up – regulation of CXCR4 might drive bortezomib resistance in multiple Myeloma

description: Bortezomib (BTZ) containing regimens induces significant antitumor response in multiple myeloma (MM) and are considered as the first-line treatment. However, resistance is still one of the unsolved problems. This study aims to explore the mechanism underlying BTZ resistance in MM. The gene expression profile (GEP) data of the GEO dataset GSE9782 was analyzed. All cases were divided into BTZ sensitive and resistant arms. Differentially expressed genes (DEGs) and later the hub genes between the two groups were screened. The key hub gene NPM1 was inhibited by shRNA and small molecule inhibitor, proliferation, apoptosis and expression of CXCR4 in myeloma cells were assayed. NPM1 was a dismal survival prognostic factor in MM, and MM patients with high NPM1 expression achieved significantly lower response rate to BTZ-containing regimens. In vitro, qRT-PCR revealed that NPM1 expression in the BTZ-resistant MM cell line KM3/BTZ (also known as KB) was significantly higher than its parental cell line KM3 cells. Knockdown of NPM1 and treatment with the NPM1 inhibitor NSC348884 both restored the sensitivity of KB cells to BTZ. Further analysis revealed that inhibition of NPM1 down-regulated CXCR4 expression at both transcriptional and translational level. In conclusion, NPM1 might causes BTZ resistance via up-regulating CXCR4 expression in MM and could be served as both a new prognostic biomarker and a promising therapeutic target.
DOI: 10.6084/m9.figshare.28719489
title: Mendelian randomization reveals causal effect of Hashimoto's thyroiditis on immune thrombocytopenic purpura

description: Patients with immune thrombocytopenic purpura (ITP) usually express thyroid antigen-specific antibodies. The purpose of this study was to explore the causal relationship between Hashimoto's thyroiditis (HT) and ITP. A two-sample Mendelian randomization (TSMR) analysis was applied to investigate the potential causal relationship between HT and ITP in European population. Five complementary methods including inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), weighted median, and weighted mode were performed in our study. Risk genes of HT and ITP were selected through Mendelian randomization (MR), and the common risk genes were further analysed by bioinformatics methods to explore the common pathogenesis of the two diseases. The MR analysis revealed a potential causal relationship between HT and risk of ITP [odds ratio (OR) = 1.22; 95% confidence interval (CI) 1.01, 1.49; <i>P</i> = 0.046]. Gene eQTL data were obtained from the IEU database. HT and ITP were respectively treated as outcome variables for MR analysis, and a total of 32 common risk genes were selected, including 12 high-risk genes and 20 low-risk genes. Functional analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis revealed that risk genes were closely related to antigen processing and presentation, and played a crucial role in the process of various viral and bacterial infections. Our study demonstrated that HT may increase the risk of ITP, and revealed the role of their common risk genes in the development of the two diseases.
DOI: 10.6084/m9.figshare.28719489.v1
title: Mendelian randomization reveals causal effect of Hashimoto's thyroiditis on immune thrombocytopenic purpura

description: Patients with immune thrombocytopenic purpura (ITP) usually express thyroid antigen-specific antibodies. The purpose of this study was to explore the causal relationship between Hashimoto's thyroiditis (HT) and ITP. A two-sample Mendelian randomization (TSMR) analysis was applied to investigate the potential causal relationship between HT and ITP in European population. Five complementary methods including inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), weighted median, and weighted mode were performed in our study. Risk genes of HT and ITP were selected through Mendelian randomization (MR), and the common risk genes were further analysed by bioinformatics methods to explore the common pathogenesis of the two diseases. The MR analysis revealed a potential causal relationship between HT and risk of ITP [odds ratio (OR) = 1.22; 95% confidence interval (CI) 1.01, 1.49; <i>P</i> = 0.046]. Gene eQTL data were obtained from the IEU database. HT and ITP were respectively treated as outcome variables for MR analysis, and a total of 32 common risk genes were selected, including 12 high-risk genes and 20 low-risk genes. Functional analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis revealed that risk genes were closely related to antigen processing and presentation, and played a crucial role in the process of various viral and bacterial infections. Our study demonstrated that HT may increase the risk of ITP, and revealed the role of their common risk genes in the development of the two diseases.