A novel gene expression signature-based on B-cell proportion to predict prognosis of patients with lung adenocarcinoma

Abstract Background This study aimed to develop a reliable immune signature based on B-cell proportion to predict the prognosis and benefit of immunotherapy in LUAD. Methods The proportion of immune cells in the TCGA-LUAD dataset was estimated using MCP-counter. The Least Absolute Shrinkage and Selector Operation was used to identify a prognostic signature and validated in an independent cohort. We used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) data and formalin-fixed paraffin-embedded (FFPE) specimens immunohistochemistry to illustrate the correlation between prognostic signature and leukocyte migration. Results We found that the relative abundance of B lineage positively correlated with overall survival. Then, we identified a 13-gene risk-score prognostic signature based on B lineage abundance in the testing cohort and validated it in a cohort from the GEO dataset. This model remained strongly predictive of prognoses across clinical subgroups. Further analysis revealed that patients with a low-risk score were characterized by B-cell activation and leukocyte migration, which was also confirmed in FFPE specimens by qRT-PCR and immunohistochemistry. Finally, this immune signature was an independent prognostic factor in the composite nomogram of clinical characteristics. Conclusions In conclusion, the 13-gene immune signature based on B-cell proportion may serve as a powerful prognostic tool in LUAD.

Download Full-text

A Novel Gene Expression Signature-Based on B-Cell Proportion to Predict Prognosis of Patients with Lung Adenocarcinoma

10.21203/rs.3.rs-585268/v1 ◽

2021 ◽

Author(s):

Zhang Yi ◽

Yin Xuewen ◽

Wang Qi ◽

Song Xuming ◽

Xia Wenjie ◽

...

Keyword(s):

B Cell ◽

Risk Score ◽

Cell Activation ◽

Gene Expression Signature ◽

Leukocyte Migration ◽

Prognostic Signature ◽

Immune Signature ◽

Qrt Pcr ◽

B Lineage ◽

Cell Proportion

Abstract Background: This study aimed to develop a reliable immune signature based on B-cell proportion to predict the prognosis and benefit of immunotherapy in LUAD.Methods: The proportion of immune cells in the TCGA-LUAD dataset was estimated using MCP-counter. The Least Absolute Shrinkage and Selector Operation was used to identify a prognostic signature and validated in an independent cohort. We used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) data and formalin-fixed paraffin-embedded (FFPE) specimens immunohistochemistry to illustrate the correlation between prognostic signature and leukocyte migration. Results: We found that the relative abundance of B lineage positively correlated with overall survival. Then, we identified a 13-gene risk-score prognostic signature based on B lineage abundance in the testing cohort and validated it in a cohort from the GEO dataset. This model remained strongly predictive of prognoses across clinical subgroups. Further analysis revealed that patients with a low-risk score were characterized by B-cell activation and leukocyte migration, which was also confirmed in FFPE specimens by qRT-PCR and immunohistochemistry. Finally, this immune signature was an independent prognostic factor in the composite nomogram of clinical characteristics.Conclusions: In conclusion, the 13-gene immune signature based on B-cell proportion may serve as a powerful prognostic tool in LUAD.

Download Full-text

Synoviocytes-derived Interleukin 35 Potentiates B Cell Response in Patients with Osteoarthritis and Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.161363 ◽

2017 ◽

Vol 45 (4) ◽

pp. 563-573 ◽

Cited By ~ 1

Author(s):

Ngar-Woon Kam ◽

Dehua Liu ◽

Zhe Cai ◽

Wah-Yan Mak ◽

Chun-Kwok Wong ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Flow Cytometry ◽

B Cells ◽

B Cell ◽

Cell Activation ◽

Synovial Fibroblasts ◽

B Cell Activation ◽

Qrt Pcr ◽

Tnf Α ◽

Factor Α

Objective.Elevated expression of interleukin 35 (IL-35) is associated with autoimmune disease, including rheumatoid arthritis (RA). The present study was undertaken to determine the functional interaction among IL-35, B cells, and stromal cells residing in the synovium of patients with RA and osteoarthritis (OA).Methods.IL-35 (EBI-3/p35) expression was investigated in RA and OA synovium using quantitative real-time PCR (qRT-PCR) and immunohistochemistry. IL-35 receptor (IL-35R) expression on B cells dissociated from synovium and periphery of patients with RA, OA, and healthy donor controls (HC) was determined by flow cytometry. The degree of B cells activation after IL-4 and/or IL-35 stimulation was measured by flow cytometry and qRT-PCR. Synovial fibroblasts (SF) purified from RA and OA synovium were cocultured with peripheral HC B cells in the presence/absence of tumor necrosis factor-α (TNF-α) and with/without anti-IL-35–blocking antibodies.Results.EBI-3/p35 transcripts were expressed in close proximity to B cells residing in RA and OA synovium. IL-35R subunits, gp130 and IL-27Rα, but not IL-12Rβ2, were expressed in B cells extracted from the synovium and periphery of patients with RA/OA. Notably, RA synovium expressed the highest level of IL-27Rα on their cell surface. IL-35 induced proliferation and IgG production in HC B cells. Cocultures of HC B cells with RASF, but not OASF, exhibited significantly elevated B cells activation. TNF-α–induced, RASF-dependent secretion of IgG in B cells is partly IL-35–dependent.Conclusion.To our knowledge, for the first time we demonstrated that synovial/peripheral B cells expressed IL-35R and were responsive to IL-35 stimulation. SF residing in RA synovium can be linked to B cell activation and maintenance in RA synovium through IL-35.

Download Full-text

A Regulatory Role for Fcγ Receptors CD16 and CD32 in the Development of Murine B Cells

Blood ◽

10.1182/blood.v92.8.2823 ◽

1998 ◽

Vol 92 (8) ◽

pp. 2823-2829 ◽

Cited By ~ 24

Author(s):

Belen de Andres ◽

Allan L. Mueller ◽

Sjef Verbeek ◽

Matyas Sandor ◽

Richard G. Lynch

Keyword(s):

Bone Marrow ◽

B Cell ◽

Cell Activation ◽

Bone Marrow Cells ◽

Normal Numbers ◽

Cell Compartment ◽

Murine Bone Marrow ◽

B Lineage ◽

B Cell Precursors ◽

B Lineage Cells

Abstract Early in development, murine B-lineage progenitor cells express two classes of IgG Fc receptors (FcγR) designated as FcγRII (CD32) and FcγRIII (CD16), but mature B lymphocytes only express FcγRII (CD32), which functions as an inhibitor of B-cell activation when it is induced to associate with mIgM. The functions of CD16 and CD32 on B-lineage precursor cells have not previously been investigated. To search for FcγR functions on developing B-lineage cells, normal murine bone marrow cells were cultured in the presence of 2.4G2, a rat monoclonal antibody that binds to CD16 and CD32, or in the presence of control normal rat IgG, and then the B-lineage compartment was analyzed for effects. Cultures that contained 2.4G2 showed enhanced growth and differentiation of B-lineage cells compared with control cultures. The enhancing effect of 2.4G2 also occurred when fluorescence-activated cell-sorted B-cell precursors (B220+, sIgM−, HSAhigh, FcγR+) from normal bone marrow were cocultured with BMS2, a bone marrow stromal cell line, but not when they were cultured in BMS2-conditioned media. The enhancement of B-lineage development induced by 2.4G2 was CD16-dependent and CD32-dependent, because 2.4G2 did not effect B-lineage growth or differentiation in cultures of bone marrow from mice in which either the gene encoding CD16 or CD32 had been disrupted. Analysis of fresh bone marrow from the CD16 gene-disrupted mice showed normal numbers and distribution of cells within the B-cell compartment, but in CD32 gene-disrupted mice, the B-cell compartment was significantly enlarged. These experiments provide several lines of evidence that the FcγR expressed on murine B-cell precursors can influence their growth and differentiation. © 1998 by The American Society of Hematology.

Download Full-text

A Regulatory Role for Fcγ Receptors CD16 and CD32 in the Development of Murine B Cells

Blood ◽

10.1182/blood.v92.8.2823.420k12_2823_2829 ◽

1998 ◽

Vol 92 (8) ◽

pp. 2823-2829 ◽

Cited By ~ 1

Author(s):

Belen de Andres ◽

Allan L. Mueller ◽

Sjef Verbeek ◽

Matyas Sandor ◽

Richard G. Lynch

Keyword(s):

Bone Marrow ◽

B Cell ◽

Cell Activation ◽

Bone Marrow Cells ◽

Normal Numbers ◽

Cell Compartment ◽

Murine Bone Marrow ◽

B Lineage ◽

B Cell Precursors ◽

B Lineage Cells

Early in development, murine B-lineage progenitor cells express two classes of IgG Fc receptors (FcγR) designated as FcγRII (CD32) and FcγRIII (CD16), but mature B lymphocytes only express FcγRII (CD32), which functions as an inhibitor of B-cell activation when it is induced to associate with mIgM. The functions of CD16 and CD32 on B-lineage precursor cells have not previously been investigated. To search for FcγR functions on developing B-lineage cells, normal murine bone marrow cells were cultured in the presence of 2.4G2, a rat monoclonal antibody that binds to CD16 and CD32, or in the presence of control normal rat IgG, and then the B-lineage compartment was analyzed for effects. Cultures that contained 2.4G2 showed enhanced growth and differentiation of B-lineage cells compared with control cultures. The enhancing effect of 2.4G2 also occurred when fluorescence-activated cell-sorted B-cell precursors (B220+, sIgM−, HSAhigh, FcγR+) from normal bone marrow were cocultured with BMS2, a bone marrow stromal cell line, but not when they were cultured in BMS2-conditioned media. The enhancement of B-lineage development induced by 2.4G2 was CD16-dependent and CD32-dependent, because 2.4G2 did not effect B-lineage growth or differentiation in cultures of bone marrow from mice in which either the gene encoding CD16 or CD32 had been disrupted. Analysis of fresh bone marrow from the CD16 gene-disrupted mice showed normal numbers and distribution of cells within the B-cell compartment, but in CD32 gene-disrupted mice, the B-cell compartment was significantly enlarged. These experiments provide several lines of evidence that the FcγR expressed on murine B-cell precursors can influence their growth and differentiation. © 1998 by The American Society of Hematology.

Download Full-text

Establishing and Validating an Aging-Related Prognostic Four-Gene Signature in Colon Adenocarcinoma

BioMed Research International ◽

10.1155/2021/4682589 ◽

2021 ◽

Vol 2021 ◽

pp. 1-17

Author(s):

Lian Zheng ◽

Yang Yang ◽

Xiaorong Cui

Keyword(s):

High Risk ◽

B Cell ◽

Gene Mutation ◽

Risk Score ◽

Cox Regression ◽

Colon Adenocarcinoma ◽

Oncological Outcome ◽

Gene Set Enrichment Analysis ◽

Prognostic Signature ◽

Gene Set

Background. Aging is a process that biological changes accumulate with time and lead to increasing susceptibility to diseases like cancer. This study is aimed at establishing an aging-related prognostic signature in colon adenocarcinoma (COAD). Methods. The transcriptome data and clinical variables of COAD patients were downloaded from TCGA database. The genes in GOBP_AGING gene set was used for prognostic evaluation by the univariate and multivariate Cox regression analyses. The model was presented by a nomogram and assessed by the Kaplan-Meier curves and calibration curves. The drug response and gene mutation were also performed to implicate the clinical significance. The GO and KEGG analyses were employed to unravel the potential functional mechanism. Results. The Gene Set Enrichment Analysis result indicates that GOBP_AGING pathway is significantly enriched in COAD samples. Four aging-related genes are finally used to construct the aging-related prognostic signature: FOXM1, PTH1R, KL, and CGAS. The COAD patients with high risk score have much shorter overall survival in both train cohort and test cohort. The nomogram is then assembled to predict 1-year, 3-year, and 5-year survival. Patients with high risk score have elevated infiltrating B cell naïve and attenuated cisplatin sensitivity. The mutation landscape shows that the TTN, FAT4, ZFHX4, APC, and OBSCN gene mutation are different between high risk score patients and low risk score patients. The differentially expressed genes between patients with high score and low score are enriched in B cell receptor signaling pathway. Conclusion. We constructed an aging-related signature in COAD patients, which can predict oncological outcome and optimize therapeutic strategy.

Download Full-text

An immune-related E2F gene expression signature provides prognostic information in patients with hepatocellular

10.1101/2021.06.26.450025 ◽

2021 ◽

Author(s):

Lu Wang ◽

Xiangdong Liu ◽

Zhongsheng Sun

Keyword(s):

Risk Score ◽

External Validation ◽

Gene Expression Signature ◽

Predictive Biomarkers ◽

Risk Groups ◽

Gene Signature ◽

High Risk Group ◽

Therapeutic Interventions ◽

Prognostic Signature ◽

Prognostic Information

Background. Hepatocellular carcinoma (HCC) is a fatal form of liver cancer. Through RB-E2F pathway or other mechanisms, E2F transcription factors impact tumorigenesis and progression of multiple cancers including HCC. We aim to develop a prognostic signature based on the expression of E2Fs for HCC patients. Methods. RNA-seq and clinical data from TCGA database were used to identify a prognostic signature based on the expression of E2Fs. Another cohort from GEO database was utilized as external validation. The risk score combined with common clinical factors were employed to establish a nomogram as a clinically-accessible tool. Tumor immune microenvironment influenced by the signature was analyzed and a competing endogenous network of the component genes has been constructed. Results. A prognostic signature dependent on the expression of two E2Fs was developed and validated, with the risk score successfully stratifying HCC patients into different risk groups. A nomogram was provided for clinical application. Patients in the high risk group exhibited significantly higher fractions of immunosuppressive cells than low-risk patients. Moreover, we revealed a mRNA-miRNA-circRNA competing endogenous network that potentially played a pivotal role in the prognosis and progression of HCC. Conclusion. This study offered a novel gene signature that could robustly identify HCC patients with poor survival and highlighted potential predictive biomarkers for therapeutic interventions.

Download Full-text

Prognostic value of an autophagy-related gene expression signature for endometrial cancer patients

10.21203/rs.3.rs-24691/v3 ◽

2020 ◽

Author(s):

Hui Wang ◽

Xiaoling Ma ◽

Jinhui Liu ◽

Yicong Wan ◽

Yi Jiang ◽

...

Keyword(s):

Endometrial Cancer ◽

High Risk ◽

Risk Score ◽

Cox Regression ◽

Risk Group ◽

Expression Profiles ◽

Gene Expression Signature ◽

Low Risk ◽

Prognostic Signature ◽

Test Set

Abstract Background: Autophagy is associated with cancer development. Autophagy-related genes play significant roles in endometrial cancer (EC), a major gynecological malignancy worldwide, but little was known about their value as prognostic markers. Here we evaluated the value of a prognostic signature based on autophagy-related genes for EC. Methods: First, various autophagy-related genes were obtained via the Human Autophagy Database and their expression profiles were downloaded from The Cancer Genome Atlas. Second, key prognostic autophagy-related genes were identified via univariat, LASSO and multivariate Cox regression analyses. Finally, a risk score to predict the prognosis of EC was calculated and validated by using the test and the entire data sets. Besides, the key genes mRNA expression were validated using quantitative real-time PCR in clinical tissue samples. Results: A total of 40 differentially expressed autophagy-related genes in EC were screened and five of them were prognosis-related (CDKN1B, DLC1, EIF4EBP1, ERBB2 and GRID1). A prognostic signature was constructed based on these five genes using the train set, which stratified EC patients into high-risk and low-risk groups (P<0.05). In terms of overall survival, the analyses of the test set and the entire set yielded consistent results (test set: p < 0.05; entire set: p < 0.05). Time-dependent ROC analysis suggested that the risk score predicted EC prognosis accurately and independently (0.674 at 1 year, 0.712 at 3 years and 0.659 at 5 years). A nomogram with clinical utility was built. Patients in the high-risk group displayed distinct mutation signatures compared with those in the low-risk group. For clinical sample validation, we found that EIF4EBP1and ERBB2 had higher level in EC than that in normal tissues while CDKN1B, DLC1 and GRID1 had lower level, which was consistent with the results predicted. Conclusions: Based on five autophagy-related genes (CDKN1B, DLC1, EIF4EBP1, ERBB2 and GRID1), our model can independently predict the OS of EC patients by combining molecular signature and clinical characteristics.

Download Full-text