High Expression of FGD3, a Putative Regulator of Cell Morphology and Motility, Is Prognostic of Favorable Outcome in Multiple Cancers

Purpose Identification of single-gene biomarkers that are prognostic of outcome can shed new insights on the molecular mechanisms that drive breast cancer and other cancers. Methods Exploratory analysis of 20,464 single-gene messenger RNAs (mRNAs) in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) discovery cohort indicates that low expression of FGD3 mRNA is prognostic for poor outcome. Prognostic significance of faciogenital dysplasia 3 (FGD3), SUSD3, and other single-gene proliferation markers was evaluated in breast cancer and The Cancer Genome Atlas (TCGA) cohorts. Results A meta-analysis of Cox regression of FGD3 mRNA as a continuous variable for overall survival of estrogen receptor (ER)–positive samples in METABRIC discovery, METABRIC validation, TCGA breast cancer, and Combination Chemotherapy in Treating Women With Breast Cancer (E2197) cohorts resulted in a combined hazard ratio (HR) of 0.69 (95% CI, 0.63 to 0.75), indicating better outcome with high expression. In the ER-negative samples, the combined meta-analysis HR was 0.72 (95% CI, 0.63 to 0.82), suggesting that FGD3 is prognostic regardless of ER status. The potential of FGD3 as a biomarker for freedom from recurrence was evaluated in the Breast International Group 1-98 (BIG 1-98; Letrozole or Tamoxifen in Treating Postmenopausal Women With Breast Cancer) study (HR, 0.85; 95% CI, 0.76 to 0.93) for breast cancer–free interval. In the Hungarian Academy of Science (HAS) breast cancer cohort, splitting on the median had an HR of 0.49 (95% CI, 0.42 to 0.58) for recurrence-free survival. A comparison of the Stouffer P value in five ER-positive cohorts showed that FGD3 ( P = 3.8E-14) outperformed MKI67 ( P = 1.06E-8) and AURKA ( P = 2.61E-5). A comparison of the Stouffer P value in four ER-negative cohorts showed that FGD3 ( P = 3.88E-5) outperformed MKI67 ( P = .477) and AURKA ( P = .820). Conclusion FGD3 was previously shown to inhibit cell migration. FGD3 mRNA is regulated by ESR1 and is associated with favorable outcome in six distinct breast cancer cohorts and four TCGA cancer cohorts. This suggests that FGD3 is an important clinical biomarker.

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High expression of JAM2 indicates better prognosis and immunotherapy response in breast cancer

10.1101/2020.12.11.421081 ◽

2020 ◽

Author(s):

Yang Peng ◽

Chi Qu ◽

Yingzi Zhang ◽

Beige Zong ◽

Yong Fu ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Mechanisms ◽

Potential Role ◽

Molecular Taxonomy ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

High Expression ◽

Cancer Tissue ◽

Mesenchymal Transition ◽

Chemotherapy Drugs

In our study, multiple databases were used to explore the potential role and underlying mechanism of junctional adhesion molecule B (JAM2) in breast cancer (BRCA). The data of JAM2 were downloaded from The Cancer Cell Line Encyclopedia (CCLE), the Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Receiver operating characteristic (ROC) curve analysis was performed to analyze the area under the curve (AUC) of JAM2 expression correlated with normal breast tissue and breast cancer tissue. Gene set enrichment analysis (GSEA) was used to identify the potential biological mechanisms of the JAM2. The expression of JAM2 mRNA was downregulated in most tumors, including BRCA, which may be due to the hypermethylated status. The AUCs, which were 0.929 and 0.887 by the logistic regression and random forest algorithms, indicated that JAM2 mRNA expression has good diagnostic value in BRCA. Univariate and multivariate analyses indicated JAM2 as an independent prognostic factor for the overall survival of BRCA patients in both the TCGA cohort (HR = 0.62, P = 0.034) and METABRIC cohort (HR = 0.77, P = 0.001). GSEA showed that multiple tumor pathways were suppressed in the JAM2 high expression group. The expression of JAM2 was most positively related to the epithelial-mesenchymal transition (EMT) score (r = 0.38; P <0.01) by the reverse-phase protein array (RPPA) analysis. Patients with high JAM2 expression may be more sensitive to immunotherapy. 18 chemotherapy drugs that patients in the JAM2 low expression group were more sensitive to being identified. Our results demonstrated the diagnostic and prognostic value of JAM2. Analysis of the molecular mechanisms indicates the potential role of JAM2 as a tumor suppressor, and high JAM2 expression may predict a better immunotherapy response in BRCA.

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RNA-seq from archival FFPE breast cancer samples: molecular pathway fidelity and novel discovery

BMC Medical Genomics ◽

10.1186/s12920-019-0643-z ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 4

Author(s):

Nathan D. Pennock ◽

Sonali Jindal ◽

Wesley Horton ◽

Duanchen Sun ◽

Jayasri Narasimhan ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Molecular Mechanisms ◽

Single Gene ◽

Prognostic Significance ◽

Breast Cancers ◽

Rna Seq ◽

Gene Set ◽

Public Data ◽

Ffpe Tissues

Abstract Background Formalin-fixed, paraffin-embedded (FFPE) tissues for RNA-seq have advantages over fresh frozen tissue including abundance and availability, connection to rich clinical data, and association with patient outcomes. However, FFPE-derived RNA is highly degraded and chemically modified, which impacts its utility as a faithful source for biological inquiry. Methods True archival FFPE breast cancer cases (n = 58), stored at room temperature for 2–23 years, were utilized to identify key steps in tissue selection, RNA isolation, and library choice. Gene expression fidelity was evaluated by comparing FFPE data to public data obtained from fresh tissues, and by employing single-gene, gene set and transcription network-based regulon analyses. Results We report a single 10 μm section of breast tissue yields sufficient RNA for RNA-seq, and a relationship between RNA quality and block age that was not linear. We find single-gene analysis is limiting with FFPE tissues, while targeted gene set approaches effectively distinguish ER+ from ER- breast cancers. Novel utilization of regulon analysis identified the transcription factor KDM4B to associate with ER+ disease, with KDM4B regulon activity and gene expression having prognostic significance in an independent cohort of ER+ cases. Conclusion Our results, which outline a robust FFPE-RNA-seq pipeline for broad use, support utilizing FFPE tissues to address key questions in the breast cancer field, including the delineation between indolent and life-threatening disease, biological stratification and molecular mechanisms of treatment resistance.

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Prognostic Significance of High Expression of ER-beta in Surgically Treated ER-Positive Breast Cancer Following Endocrine Therapy

Journal of Breast Cancer ◽

10.4048/jbc.2012.15.1.79 ◽

2012 ◽

Vol 15 (1) ◽

pp. 79 ◽

Cited By ~ 9

Author(s):

Tae-Jung Kim ◽

Ahwon Lee ◽

Yeong-Jin Choi ◽

Byung Joo Song ◽

Hyeon Woo Yim ◽

...

Keyword(s):

Breast Cancer ◽

Endocrine Therapy ◽

Prognostic Significance ◽

High Expression ◽

Er Positive ◽

Positive Breast Cancer

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Expression and potential molecular mechanisms of miR‑204‑5p in breast cancer, based on bioinformatics and a meta‑analysis of 2,306�cases

Molecular Medicine Reports ◽

10.3892/mmr.2018.9764 ◽

2018 ◽

Author(s):

Kai‑Teng Cai ◽

An‑Gui Liu ◽

Ze‑Feng Wang ◽

Hang‑Wei Jiang ◽

Jing‑Jing Zeng ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Mechanisms ◽

Meta Analysis

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Influence of ABCB1 C3435T gene polymorphisms on tumor response to neoadjuvant chemotherapy in locally advanced breast cancer patients from Northeastern Brazil.

10.21203/rs.2.16585/v1 ◽

2019 ◽

Author(s):

Diego de Aragão Bezerra ◽

Jose Juvenal Linhares ◽

Emmanuelle Coelho Noronha ◽

Kaio César Simiano Tavares ◽

André Saraiva Leão Marcelo Antunes ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Locally Advanced Breast Cancer ◽

Single Gene ◽

Locally Advanced ◽

Northeastern Brazil ◽

P Value ◽

Female Population ◽

C3435t Polymorphism ◽

Response To Neoadjuvant Chemotherapy

Abstract Background: Breast cancer (BC) is the most common tumor and the leading cause of cancer-related death among the female population worldwide. To evaluate the association between the ABCB1 C3435T single gene nucleotide polymorphisms (SNPs) with the response to neoadjuvant chemotherapy in women with breast cancer. Methods: This study included 32 female patients who received neoadjuvant chemotherapy. The polymorphisms were genotyped through real-time allele-specific polymerase chain reaction (PCR). The statistical analysis was performed using the Fisher's exact test or Pearson's chi-square test in the Statistical Package for Social Sciences (SPSS) version 20.0 software. Results: The genotypes found for the C3435T polymorphism were in Hardy-Weinberg equilibrium and their genotypic distributions were CC= 10 (31.1%), CT= 14 (43.8%), and TT= 08 (25.0%) with χ2: 0.86 and p-value > 0.05. Allele frequencies were C = 0.54 and T = 0.46. There were no significant statistical differences between genotypes considering the response to neoadjuvant chemotherapy and immunohistochemistry; the presence of the T allele was associated with worsen axillary status response to neoadjuvant chemotherapy. Conclusion: No definite association between the presence of C3435T polymorphism and the response to neoadjuvant chemotherapy was observed. Further studies in Brazil involving larger samples will contribute to validating the results of this study. Keywords: Breast cancer; Neoadjuvant Chemotherapy; Polymorphisms; Gene ABCB1

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Prognostic significance of occult lymph node metastases in breast cancer: a meta-analysis

10.21203/rs.3.rs-337175/v1 ◽

2021 ◽

Author(s):

Guixin Wang ◽

Shuhao Zhang ◽

Meiling Wang ◽

Lin Liu ◽

Yaqian Liu ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Lymph Nodes ◽

Meta Analysis ◽

Prognostic Significance ◽

Axillary Lymph Nodes ◽

Axillary Lymph ◽

Occult Metastases ◽

Node Metastases ◽

Disease Free

Abstract Background: Occult metastases in axillary lymph nodes have been reported to be associated with poor prognosis in patients with breast cancer. However, studies on the prognostic value of occult metastases remain controversial. This meta-analysis aimed to evaluate the prognostic significance of occult lymph node metastases in breast cancer.Methods: Studies published published until May, 2020, which retrospectively examined negative lymph nodes by step sectioning and/or immunohistochemistry, were retrieved from MEDLINE, EMBASE, CNKI, and Cochrane Library. The pooled Relative risk (RR) with 95% confidence interval (95% CI) for overall survival (OS) and disease-free survival (DFS) were calculated to appraise the associations between occult metastases and prognosis.Results: The results showed patients with occult metastases in axillary lymph nodes had poorer five-year DFS (RR = 0.930; 95% CI = 0.907–0.954) and OS (RR = 0.972; 95% CI = 0.954–0.990). Furthermore, the DFS (RR = 0.887; 95% CI = 0.810–0.972) and OS (RR = 0.896; 95% CI = 0.856–0.939) of patients with occult metastases were much lower after a ten-year follow-up.Conclusions: Occult metastases in the axillary lymph nodes of patients with breast cancer are associated with poorer disease-free and overall survival. Occult metastases might serve as a predictive factor of survival outcomes in patients with breast cancer.

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Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer

British Journal of Cancer ◽

10.1038/s41416-019-0589-0 ◽

2019 ◽

Vol 121 (9) ◽

pp. 776-785 ◽

Cited By ~ 2

Author(s):

Chitra Joseph ◽

Sara Al-Izzi ◽

Mansour Alsaleem ◽

Sasagu Kurozumi ◽

Michael S Toss ◽

...

Keyword(s):

Breast Cancer ◽

Patient Outcome ◽

Distant Metastasis ◽

Prognostic Significance ◽

Retinoid X Receptor ◽

Cancer Tissue ◽

Lower Grade ◽

Breast Cancer Specific Survival ◽

Cancer Specific Survival ◽

Er Positive

Abstract Background Retinoid X Receptor Gamma (RXRG) is a member of the nuclear receptor superfamily and plays a role in tumour suppression. This study aims to explore the prognostic significance of RXRG in breast cancer. Methods Primary breast cancer tissue microarrays (n = 923) were immuno-stained for RXRG protein and correlated with clinicopathological features, and patient outcome. Results Nuclear RXRG expression was significantly associated with smaller tumour size (p = 0.036), lower grade (p < 0.001), lobular histology (p = 0.016), lower Nottingham Prognostic Index (p = 0.04) and longer breast cancer-specific survival (p < 0.001), and longer time to distant metastasis (p = 0.002). RXRG expression showed positive association with oestrogen receptor (ER)-related biomarkers: GATA3, FOXA1, STAT3 and MED7 (all p < 0.001) and a negative correlation with the Ki67 proliferation marker. Multivariate analysis demonstrated RXRG protein as an independent predictor of longer breast cancer-specific survival and distant metastasis-free survival. In the external validation cohorts, RXRG expression was associated with improved patients’ outcome (p = 0.025). In ER-positive tumours, high expression of RXRG was associated with better patient outcome regardless of adjuvant systemic therapy. ER signalling pathway was the top predicted master regulator of RXRG protein expression (p = 0.005). Conclusion This study provides evidence for the prognostic value of RXRG in breast cancer particularly the ER-positive tumours.

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Clinicopathological and Prognostic Significance of CBX3 Expression in Human Cancer: a Systematic Review and Meta-analysis

Disease Markers ◽

10.1155/2020/2412741 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Hexin Lin ◽

Xin Zhao ◽

Lu Xia ◽

Jiabian Lian ◽

Jun You

Keyword(s):

Malignant Tumors ◽

Human Cancer ◽

Meta Analysis ◽

Univariate Analysis ◽

Prognostic Significance ◽

Cancer Prognosis ◽

High Expression ◽

Clinicopathological Parameters ◽

Malignant Neoplasms ◽

Tumor Type

Background. Chromebox protein homolog 3 (CBX3) as a member of the heterochromatin-associated protein 1 (HP1) family has been reported to be overexpressed in human cancer tissues. Numerous studies have shown the relationship between the CBX3 expression and clinicopathological factor or prognosis in malignant tumors, but their results are inconsistent. To address these results, a meta-analysis was described to investigate the prognostic value and clinicopathological significance of CBX3 expression in human malignant neoplasms. Methods. PubMed, Web of Science, Embase, and Chinese National Knowledge Infrastructure (CNKI) were used to search eligible literatures, including publications prior to September 2019. The role of CBX3 in cancer prognosis and clinicopathological characteristics was assessed by pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). Results. Eleven studies with 1682 cancer patients were enrolled in this meta-analysis. This analysis demonstrated that the patients’ increased CBX3 expression was significantly associated with poor overall survival (OS) (univariate analysis: HR = 1.81 , 95% CI 1.46-2.25; multivariate analysis: HR = 1.95 , 95% CI 1.63-2.34). Subgroups analysis by tumor type also indicated that high expression of CBX3 was correlated with poor OS in tongue squamous cell carcinoma ( HR = 3.31 , 95% CI 2.03-5.39), lung cancer ( HR = 1.66 , 95% CI 1.21-2.29), genitourinary cancer ( HR = 2.03 , 95% CI 1.15-3.58), and digestive cancer ( HR = 1.48 , 95% CI 1.23-1.79). For clinicopathological features, high expression of CBX3 was associated with lymph node metastasis ( OR = 2.96 , 95% CI 1.42-6.20) and lager tumor size ( OR = 1.60 , 95% CI 1.12-2.28). Conclusion. The results of this meta-analysis indicated that CBX3 expression may be a novel biomarker for predicting patient prognosis and clinicopathological parameters in multiple human cancer.

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Prognostic significance of Ki-67 labeling index after short-term presurgical tamoxifen in women with ER-positive breast cancer

Annals of Oncology ◽

10.1093/annonc/mdq427 ◽

2011 ◽

Vol 22 (3) ◽

pp. 582-587 ◽

Cited By ~ 59

Author(s):

A. DeCensi ◽

A. Guerrieri-Gonzaga ◽

S. Gandini ◽

D. Serrano ◽

M. Cazzaniga ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Significance ◽

Labeling Index ◽

Short Term ◽

Ki 67 ◽

Er Positive ◽

Positive Breast Cancer

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The Clinicopathological and Prognostic Significance of IDO1 Expression in Human Solid Tumors: Evidence from a Systematic Review and Meta-Analysis

Cellular Physiology and Biochemistry ◽

10.1159/000492849 ◽

2018 ◽

Vol 49 (1) ◽

pp. 134-143 ◽

Cited By ~ 18

Author(s):

Cheng-Peng Yu ◽

Shu-Fang Fu ◽

Xuan Chen ◽

Jing Ye ◽

Yuan Ye ◽

...

Keyword(s):

Systematic Review ◽

Cancer Patients ◽

Solid Tumors ◽

Meta Analysis ◽

Prognostic Significance ◽

High Expression ◽

Cochrane Library ◽

Odds Ratios ◽

Ido1 Expression ◽

Human Solid Tumors

Background/Aims: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme catalyzing the initial and rate-limiting steps in the kynurenine pathway, which converts tryptophan into kynurenine. Upregulation of IDO1 decreases tryptophan levels and increases the accumulation of kynurenine and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence has shown that IDO1 is highly expressed in various cancer types and associated with poor prognosis of cancer patients. However, the results were inconsistent. Methods: We searched the Web of Science, PubMed, Embase and Cochrane library databases to identify studies evaluating the prognostic value of IDO1 in cancer patients. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by using fixed-effects/random-effects models. Results: This systematic review and meta-analysis included 2706 patients from 24 articles. The results indicated a shorter overall survival in patients with high expression of IDO1 (hazard ratio [HR] = 2.03, 95% confidence interval [CI]: 1.56-2.63). Furthermore, disease-free survival was worse in patients with high expression of IDO1 (HR = 2.47, 95% CI: 1.46-4.20). Additionally, the pooled odds ratios (ORs) showed that increased IDO1 was significantly associated with tumor differentiation (OR = 1.81, 95% CI: 1.05-3.12), distant metastasis (OR = 1.45, 95% CI: 1.02-2.06), and poor clinical stage (OR = 1.89, 95% CI: 1.13-3.17). However, no significant correlation was observed of increased IDO1 expression with age, sex, lymph node metastasis, and tumor size. Conclusion: High expression of IDO1 is associated with poor clinical outcomes. IDO1 could serve as a biomarker of prognosis and a potential predictive factor of clinicopathology in various cancers. Further studies should be performed to verify the clinical utility of IDO1 in human solid tumors.

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