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Background: To evaluate the clinical research related to the level and integrity of circulating free DNA (cfDNA) in the plasma of patients with multiple myeloma (MM). Methods: The plasma samples of 56 patients with newly diagnosed MM and 60 healthy volunteers were collected. ALU247 fragment and ALU115 fragment were used as target genes, and quantitative polymerase chain reaction (qPCR) was used to assess the plasma of the patient and healthy control groups. The cfDNA level in MM was analyzed, and the ALU247/ALU115 ratio was used to calculate the integrity of cfDNA. The correlation between the cfDNA level and integrity and the clinical characteristics of patients with primary MM was analyzed, and their value in efficacy monitoring and prognostic evaluation was evaluated. Results: The plasma concentrations of ALU247 and ALU115 and the integrity of cfDNA in patients with primary MM were significantly higher than those in the healthy controls (P<0.05). The ALU247 fragment concentration was markedly correlated with the Durie-Salmon (D-S), International Staging System (ISS), and Revised-International Staging System (R-ISS) stages (P<0.05). After three courses of induction chemotherapy, the levels of ALU247, ALU115, and cfDNA integrity in both groups were lower than those before chemotherapy (P<0.05). Patients with curative effects of CR, sCR, and VGPR were classified into the ≥ very good partial response (VGPR) group (n=38), while those with curative effects of PR and SD were allocated into the
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Objectives: To evaluate the role of CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) in tumor microenvironment and cancer immunotherapy and explore its potential mechanism. Method: The cancer genome map was obtained from the UCSC Xena database. RNAseq data from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases were utilized for evaluating the expression and prognostic value of CMTM3 through survival data of clinical trials. The enrichment analysis of CMTM3 was performed using the R package "clusterProfiler." The scores of immune cell infiltration in TCGA samples were downloaded from the ImmuCellAI database and TIMER2 database, and the relationship between both immune cell invasion and CMTM3 expression was investigated. Immunological activation and suppression genes, immune checkpoints, chemokines, and their receptors were all investigated in relation to CMTM3. Results: Most tumor types had varied levels of CMTM3 expression and predicted poor survival status. The CMTM3 expression is closely associated with cancer-associated fibroblasts, macrophages, myeloid dendritic cells, endothelial cells, immune activation genes, immune suppressor genes, immune checkpoints, chemokines, and related receptors. Conclusion: Our data reveal that CMTM3 might be used as a cancer biomarker. CMTM3 may work in conjunction with other immunological checkpoints to alter the immune milieu, which could lead to the establishment of new immunotherapy medicines.
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Background: Most previous studies have focused on the intrinsic carcinogenic pathways of tumors; however, little is known about the potential role of N6-methyladenosine (m6A) methylation in the tumor immune microenvironment (TIME). To better diagnose and treat acute myeloid leukemia (AML), we sought to examine the correlation between m6A regulatory factors and immune infiltration in cases of AML. At the same time, a prognostic model was constructed to predict the survival of AML. Methods: We extracted data from The Cancer Genome Atlas (TCGA) database, including ribonucleic acid sequencing (RNA-seq) transcriptome data and data on the corresponding clinical characteristics of AML patients. We identified two m6A modification patterns with distinct clinical outcomes and found a significant relationship between them. Simultaneous discovery of distinct m6A clusters associated with the tumor immune microenvironment [immune cell types and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm] are closely related. Next, we implemented Lasso (Least Absolute Shrinkage and Selection Operator) Cox regression to build a predictive model in the 2-m6A regulator TCGA dataset to further explore m6A prognostic features in AML, and perform correlation validation. Results: We identified 2 molecular subtypes (Clusters 1 and 2) by the consistent clustering of significant m6A regulators in AML. Cluster 2 was associated with a higher immune score and obvious immune cell infiltration, and thus patients in Cluster 2 had a poorer prognosis than those in Cluster 1 (P<0.05). Additionally, the 2 m6A-related signatures representing the independent prognostic factors in AML were screened to construct a prognostic risk-score model. We found that patients with low-risk scores had higher immune scores than those with high-risk scores (P<0.05). Conclusions: Our research confirmed that m6A methylation plays an important role in AML. Further provide new directions for the prognosis and treatment of AML.
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Background: Multiple myeloma (MM) is a B-lymphocyte-derived malignancy. It ranks as the second most common hematological malignancy, with relatively high morbidity and mortality. However, the molecular mechanisms of MM occurrence and development remain elusive. This study found that long non-coding RNA AL928768.3 (lncRNA AL) was abnormally expressed in MM samples. However, the effect and molecular mechanism of lncRNA AL on the occurrence and development of MM remains unclear. Methods: Bone marrow fluids of MM patients (n=54) and volunteers (n=13) were collected and CD138+ cells were isolated. The expression level of lncRNA AL in MM cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the correlation between the expression level of lncRNA AL and the clinicopathological features of patients was analyzed. Lentiviral vectors targeting lncRNA AL knockdown were constructed and transfected into cells. After transfection, the effects of lncRNA AL knockdown on MM cell proliferation and the cell cycle were detected by the CCK-8 assay, clone formation assay, and flow cytometry. The effect of lncRNA AL knockdown on MM cell cycle-related proteins was detected by Western blot. In addition, tumorigenicity experiments were performed in nude mice to detect the effect of lncRNA AL knockdown on MM cell proliferation in vivo. Results: LncRNA AL was highly expressed in MM patient samples and cell lines, and was significantly correlated with the disease stage of patients. Knockdown of lncRNA AL significantly inhibited the proliferation and colony formation of MM cells and induced cell cycle arrest in G0/G1 phase. Western blot analysis showed that knockdown of lncRNA AL significantly inhibited the expression of CDK2 and cyclin D1 and promoted the expression of cyclin suppressor p21. Knockdown of lncRNA AL significantly inhibited the proliferation of MM cells in nude mice. Conclusions: LncRNA AL was highly expressed in MM patients. Knockdown of this gene significantly inhibited the proliferative ability of MM cells and induced cell cycle arrest in G0/G1 phase. Therefore, lncRNA AL may be a novel biological target molecule for the early diagnosis, treatment, and prognostic evaluation of MM patients.