Dataset Information

Matrix Metallopeptidase 14: A Candidate Prognostic Biomarker for Diffuse Large B-Cell Lymphoma.

ABSTRACT: Background:Matrix metallopeptidase 14 (MMP14) is an important gene in the regulation of T-cell function. However, the correlation between MMP14 expression, prognosis, and immune cell infiltration in diffuse large B-cell lymphoma (DLBCL) remains unclear. Methods:We investigated the influence of MMP14 on clinical prognosis using data obtained from three Gene Expression Omnibus (GEO) database sets (GSE98588, GSE10846, and GSE4475). The expression of MMP14 was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA). The correlation between MMP14 and immune cell infiltration was investigated using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Tumor Immune Estimation Resource (TIMER) tools. In addition, the correlation between MMP14 expression and immune gene markers was analyzed by TIMER and GEPIA. Results:MMP14 expression positively correlated with favorable progression-free survival (PFS; GSE98588, P = 0.02) and overall survival (OS; GSE98588, P = 0.003; GSE10846, P = 5.517e-05; and GSE4475, P = 9.85e-04). Moreover, MMP14 expression was higher in DLBCL tumors than in normal tissues. Regarding clinical characteristics, high MMP14 expression was found to be correlated with race. MMP14 expression was also correlated with immune cell infiltration and had a remarkable correlation with various immune marker sets. It was found that M0 macrophages were the immune cells most related to survival, decreasing with the increase in Ann Arbor clinical stage. The results especially showed that MMP14 was a prognostic biomarker and related to the macrophages M0. Conclusion:The results suggest that MMP14 is a novel prognostic molecular marker for DLBCL and is related to the immune cell infiltration, especially related to the macrophages M0. Our study provides insights for understanding the potential roles of MMP14 in tumor immunology and its suitability as a prognosis biomarker in DLBCL.

SUBMITTER: Yin C

PROVIDER: S-EPMC7473157 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Matrix Metallopeptidase 14: A Candidate Prognostic Biomarker for Diffuse Large B-Cell Lymphoma.

Yin Chengliang C Zhang Junyan J Shen Ming M Gu Zhenyang Z Li Yan Y Xue Wanguo W Shi Jinlong J Huang Wenrong W

Frontiers in oncology 20200820

<h4>Background</h4>Matrix metallopeptidase 14 (MMP14) is an important gene in the regulation of T-cell function. However, the correlation between MMP14 expression, prognosis, and immune cell infiltration in diffuse large B-cell lymphoma (DLBCL) remains unclear.<h4>Methods</h4>We investigated the influence of MMP14 on clinical prognosis using data obtained from three Gene Expression Omnibus (GEO) database sets (GSE98588, GSE10846, and GSE4475). The expression of MMP14 was analyzed using the Gene ...[more]

PMID: 32974187

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Project description:Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma with an increased tendency to relapse or refractoriness. RAB39B, a member of the Ras-oncogene superfamily, is associated with a variety of tumors. Nevertheless, the role of RAB39B in DLBCL is still unknown. This study aimed to identify the role of RAB39B in DLBCL using integrated bioinformatics analysis. Methods: RAB39B expression data were examined using TIMER, UCSC, and GEO databases. The LinkedOmics database was used to study the genes and signaling pathways related to RAB39B expression. A Protein-protein interaction network was performed in STRING. TIMER was used to analyze the correlation between RAB39B and infiltrating immune cells. The correlation between RAB39B and m6A-related genes in DLBCL was analyzed using TCGA data. The RAB39B ceRNA network was constructed based on starBase and miRNet2.0 databases. Drug sensitivity information was obtained from the GSCA database. Results: RAB39B was highly expressed in multiple tumors including DLBCL. The protein-protein interaction network showed enrichment of autophagy and RAS family proteins. Functional enrichment analysis of RAB39B co-expression genes revealed that RAB39B was closely related to DNA replication, protein synthesis, cytokine-cytokine receptor interaction, JAK-STAT signaling pathway, NF-kappa B signaling pathway, and autophagy. Immune infiltrate analysis showed that the amount of RAB39B was negatively correlated with iDC, Tem, and CD8 T-cell infiltration. CD4+ T cell and DC were negatively correlated with CNV of RAB39B. DLBCL cohort analysis found that RAB39B expression was related to 14 m6A modifier genes, including YTHDC1, YTHDC2, YTHDF1, YTHDF2, YTHDF3, RBMX, ZC3H13, METTL14, METTL3, RBM15, RBM15B, VIRMA, FTO, and ALKBH5. We constructed 14 possible ceRNA networks of RAB39B in DLBCL. The RAB39B expression was associated with decreased sensitivity of chemotherapy drugs such as dexamethasone, doxorubicin, etoposide, vincristine, and cytarabine and poor overall survival in DLBCL. In vitro experiments showed that RAB39B was associated with proliferation, apoptosis, and drug sensitivity of DLBCL cells. Conclusion: RAB39B is abnormally elevated and related to drug resistance and poor OS in DLBCL, which may be due to its involvement in immune infiltration, m6A modification, and regulation by multiple non-coding RNAs. RAB39B may be used as an effective biomarker for the diagnosis and treatment of DLBCL.

Project description:BackgroundCancer cachexia is known to adversely affect the clinical course in patients with malignant lymphoma. The cachexia index (CXI) is a potential biomarker of cancer cachexia, and its implications for the prognosis and treatment outcome of lung cancer and aggressive lymphoma has been assessed in previous studies.MethodsA total of 267 patients diagnosed with diffuse large B-cell lymphoma who were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immunochemotherapy were retrospectively reviewed. The CXI was calculated as the skeletal muscle index (SMI) × serum albumin/neutrophil-lymphocyte ratio (NLR). Although previous studies measured the SMI using the muscles of the L3 vertebral level, the present study used both the L3 vertebral muscles and the pectoralis muscles (PM) at the T4 vertebral level to measure the SMI. Depending on the type of muscles used, the CXI was termed the L3-CXI or PM-CXI. Using sex-specific cutoff values for CXI, the patients were categorized as follows: (i) high-CXI group (high L3-CXI and high PM-CXI), (ii) intermediate-CXI group (high L3-CXI and low PM-CXI), and (iii) low-CXI group (low L3-CXI and low PM-CXI).ResultsComplete responses to R-CHOP were obtained in 145/173 (83.8%), 25/36 (69.4%), and 27/57 (47.4%) patients in the high-CXI, intermediate-CXI, and low-CXI groups, respectively (P < 0.001). Treatment-related anaemia (15.6%, 30.6%, and 26.3%, P = 0.038), thrombocytopenia (21.4%, 36.1%, and 43.9%, P < 0.001), febrile neutropenia (23.7%, 44.4%, and 36.8%, P = 0.022), and any nonhaematologic toxicity (31.2%, 44.4%, and 54.4%, P = 0.001) of Grade 3 or more were more common in the lower CXI groups than in the higher-CXI groups. Early treatment discontinuation for reasons other than lymphoma progression also occurred more frequently in the low-CXI group (24/57, 42.1%) compared with the intermediate-CXI (5/36, 13.9%) and high-CXI (18/173, 10.4%) groups (P < 0.001). Median overall survival in the high-CXI, intermediate-CXI, and low-CXI groups was not reached, 50.6 months, and 14.5 months, respectively (p < 0.001). Multivariable analysis showed that low CXI was an independent negative prognostic factor for overall survival (hazard ratio 2.103, 95% confidence interval 1.278-3.460, P = 0.003).ConclusionsWe suggest that in patients with diffuse large B-cell lymphoma, the CXI is a biomarker for cancer cachexia that can predict survival, treatment response, treatment-related toxicity, and compliance with R-CHOP. Patients were more clearly stratified by this new CXI category compared with the classifications described in previous studies.

Dataset Information

Matrix Metallopeptidase 14: A Candidate Prognostic Biomarker for Diffuse Large B-Cell Lymphoma.

Publications

Matrix Metallopeptidase 14: A Candidate Prognostic Biomarker for Diffuse Large B-Cell Lymphoma.

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