Degree of stemness predicts micro-environmental response and clinical outcomes of diffuse large B-cell lymphoma and identifies a potential targeted therapy
Some cells within a diffuse large B-cell lymphoma (DLBCL) have the genotype of a stem cell, the proportion of which is termed degree of stemness. We interrogated correlations between the degree of stemness with immune and stromal cell scores and clinical outcomes in persons with DLBCL. We evaluated...
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| Format: | Article |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1012242/full |
| _version_ | 1811221470171365376 |
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| author | Fang Hu Fang Hu Huan Li Huan Li Lei Li Robert Peter Gale Yuanbin Song Yuanbin Song Shuiqin Chen Shuiqin Chen Yang Liang Yang Liang |
| author_facet | Fang Hu Fang Hu Huan Li Huan Li Lei Li Robert Peter Gale Yuanbin Song Yuanbin Song Shuiqin Chen Shuiqin Chen Yang Liang Yang Liang |
| author_sort | Fang Hu |
| collection | DOAJ |
| description | Some cells within a diffuse large B-cell lymphoma (DLBCL) have the genotype of a stem cell, the proportion of which is termed degree of stemness. We interrogated correlations between the degree of stemness with immune and stromal cell scores and clinical outcomes in persons with DLBCL. We evaluated gene expression data on 1,398 subjects from Gene Expression Omnibus to calculate the degree of stemness. Subjects were classified into low- and high-stemness cohorts based on restricted cubic spline plots. Weighted gene co-expression network analysis (WGCNA) was used to screen for stemness-related genes. Immune and stromal scores correlated with the degree of stemness (both P < 0.001). A high degree of stemness correlated with a shorter progression-free survival (PFS; Hazard Ratio [HR; 95% Confidence Interval [CI] =1.90 (1.37, 2.64; P < 0.001) and a shorter survival (HR = 2.29 (1.53, 3.44; P < 0.001). CDC7 expression correlated with the degree of stemness, and CDC7-inhibitors significantly increased apoptosis (P < 0.01), the proportion of cells in G1 phase (P < 0.01), and inhibited lymphoma growth in a mice xenograft model (P = 0.04). Our data indicate correlations between the degree of stemness, immune and stromal scores, PFS, and survival. These data will improve the prediction of therapy outcomes in DLBCL and suggest potential new therapies. |
| first_indexed | 2024-04-12T08:01:05Z |
| format | Article |
| id | doaj.art-7efbf16e087f4612a96cf2c90f20e354 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T08:01:05Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7efbf16e087f4612a96cf2c90f20e3542022-12-22T03:41:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10122421012242Degree of stemness predicts micro-environmental response and clinical outcomes of diffuse large B-cell lymphoma and identifies a potential targeted therapyFang Hu0Fang Hu1Huan Li2Huan Li3Lei Li4Robert Peter Gale5Yuanbin Song6Yuanbin Song7Shuiqin Chen8Shuiqin Chen9Yang Liang10Yang Liang11Sate Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaSate Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of ICU, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaHaematology Research Centre, Department of Immunology and Inflammation, Haematology Research Centre, Imperial College London, London, United KingdomSate Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaSate Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaSate Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, ChinaDepartment of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaSome cells within a diffuse large B-cell lymphoma (DLBCL) have the genotype of a stem cell, the proportion of which is termed degree of stemness. We interrogated correlations between the degree of stemness with immune and stromal cell scores and clinical outcomes in persons with DLBCL. We evaluated gene expression data on 1,398 subjects from Gene Expression Omnibus to calculate the degree of stemness. Subjects were classified into low- and high-stemness cohorts based on restricted cubic spline plots. Weighted gene co-expression network analysis (WGCNA) was used to screen for stemness-related genes. Immune and stromal scores correlated with the degree of stemness (both P < 0.001). A high degree of stemness correlated with a shorter progression-free survival (PFS; Hazard Ratio [HR; 95% Confidence Interval [CI] =1.90 (1.37, 2.64; P < 0.001) and a shorter survival (HR = 2.29 (1.53, 3.44; P < 0.001). CDC7 expression correlated with the degree of stemness, and CDC7-inhibitors significantly increased apoptosis (P < 0.01), the proportion of cells in G1 phase (P < 0.01), and inhibited lymphoma growth in a mice xenograft model (P = 0.04). Our data indicate correlations between the degree of stemness, immune and stromal scores, PFS, and survival. These data will improve the prediction of therapy outcomes in DLBCL and suggest potential new therapies.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1012242/fulldiffuse large B-cell lymphomastem cellstargeted therapysingle-sample gene set enrichment analysisweighted gene co-expression network analysisdequalinium chloride |
| spellingShingle | Fang Hu Fang Hu Huan Li Huan Li Lei Li Robert Peter Gale Yuanbin Song Yuanbin Song Shuiqin Chen Shuiqin Chen Yang Liang Yang Liang Degree of stemness predicts micro-environmental response and clinical outcomes of diffuse large B-cell lymphoma and identifies a potential targeted therapy Frontiers in Immunology diffuse large B-cell lymphoma stem cells targeted therapy single-sample gene set enrichment analysis weighted gene co-expression network analysis dequalinium chloride |
| title | Degree of stemness predicts micro-environmental response and clinical outcomes of diffuse large B-cell lymphoma and identifies a potential targeted therapy |
| title_full | Degree of stemness predicts micro-environmental response and clinical outcomes of diffuse large B-cell lymphoma and identifies a potential targeted therapy |
| title_fullStr | Degree of stemness predicts micro-environmental response and clinical outcomes of diffuse large B-cell lymphoma and identifies a potential targeted therapy |
| title_full_unstemmed | Degree of stemness predicts micro-environmental response and clinical outcomes of diffuse large B-cell lymphoma and identifies a potential targeted therapy |
| title_short | Degree of stemness predicts micro-environmental response and clinical outcomes of diffuse large B-cell lymphoma and identifies a potential targeted therapy |
| title_sort | degree of stemness predicts micro environmental response and clinical outcomes of diffuse large b cell lymphoma and identifies a potential targeted therapy |
| topic | diffuse large B-cell lymphoma stem cells targeted therapy single-sample gene set enrichment analysis weighted gene co-expression network analysis dequalinium chloride |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1012242/full |
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