Copy number of 8q24.3 drives HSF1 expression and patient outcome in cancer: an individual patient data meta-analysis

Abstract Background The heat-shock transcription factor 1 (HSF1) has been linked to cell proliferation and survival in cancer and has been proposed as a biomarker for poor prognosis. Here, we assessed the role of HSF1 expression in relation to copy number alteration (CNA) and cancer prognosis. Methods Using 10,287 cancer genomes from The Cancer Genome Atlas and Cbioportal databases, we assessed the association of HSF1 expression with CNA and cancer prognosis. CNA of 8q24.3 was categorized as diploid (reference), deletion (fewer copies), gain (+ 1 copy) and amplification (≥ + 2 copies). Multivariate logistic regression modeling was used to assess 5-year survival among those with a first cancer diagnosis and complete follow-up data (N = 9568), categorized per anatomical location and histology, assessing interaction with tumor stage, and expressed as odds ratios and 95% confidence intervals. Results We found that only 54.1% of all tumors have a normal predicted 8q24.3 copy number and that 8q24.3 located genes including HSF1 are mainly overexpressed due to increased copies number of 8q24.3 in different cancers. The tumor of patients having respectively gain (+ 1 copy) and amplification (≥ + 2 copies) of 8q24.3 display a global increase of 5-year mortality (odds ratio = 1.98, 95% CI 1.22–3.21) and (OR = 2.19, 1.13–4.26) after full adjustment. For separate cancer types, tumor patients with 8q24.3 deletion showed a marked increase of 5-year mortality in uterine (OR = 4.84, [2.75–8.51]), colorectal (OR = 4.12, [1.15–14.82]), and ovarian (OR = 1.83, [1.39–2.41]) cancers; and decreased mortality in kidney cancer (OR = 0.41, [0.21–0.82]). Gain of 8q24.3 resulted in significant mortality changes in 5-year mortality for cancer of the uterus (OR = 3.67, [2.03–6.66]), lung (OR = 1.76, [1.24–2.51]), colorectal (OR = 1.75, [1.32–2.31]) cancers; and amplification for uterine (OR = 4.58, [1.43–14.65]), prostate (OR = 4.41 [3.41–5.71]), head and neck (OR = 2.68, [2.17–3.30]), and stomach (OR = 0.56, [0.36–0.87]) cancers. Conclusions Here, we show that CNAs of 8q24.3 genes, including HSF1, are tightly linked to 8q24.3 copy number in tumor patients and can affect patient outcome. Our results indicate that the integration of 8q24.3 CNA detection may be a useful predictor for cancer prognosis.

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The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: a Systematic Review and Meta-analysis

10.21203/rs.3.rs-135089/v1 ◽

2020 ◽

Author(s):

Kai Gan ◽

Yue Gao ◽

KuangZheng Liu ◽

Bin Xu ◽

Ming Chen

Keyword(s):

Bladder Cancer ◽

Clinical Significance ◽

Prognostic Value ◽

Meta Analysis ◽

Growth Factor Receptor ◽

Tumor Stage ◽

The Cancer Genome Atlas ◽

Her2 Expression ◽

Large Tumor ◽

Normal Tissues

Abstract Objective: Human Epidermal Growth Factor Receptor 2 (HER2) is highly expressed in a variety of tumors and associated with patients’ prognosis, but its role in bladder cancer remains unclear. We conducted this meta-analysis to explore the clinical significance and prognostic value of HER2 in bladder cancer and its potentiality as an immunotherapy target.Methods: PubMed was searched for studies published between January 1, 2000 and January 1, 2020. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to investigate the relationship between HER2 and bladder cancer. UALCAN website was used to obtain TCGA (The cancer genome atlas) database.Results: Our study includes 14 articles, 1398 patients. HER2 expression was significantly higher in bladder cancer than in normal tissues. Our meta-analysis results did not reveal any effect of gender on the expression of HER2 levels in bladder cancer patients. However, HER2 expression in male patients was significantly higher than that in women according to TCGA databases. HER2 expression was also associated with carcinoma in situ, multifocal tumors, large tumor size, high tumor stage and grade, lymph node metastases, risk of recurrence and progression, low recurrence-free survival (RFS) rate. HER2 expression status had no effect on overall survival.Conclusions: Our meta-analysis showed that HER2 expression was related to pathological malignancy and poor prognosis in bladder cancer which indicated that it could be used as an effective biomarker and therapeutic target.

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Identification of Key Genes Driving Tumor Associated Macrophage Migration and Polarization Based on Immune Fingerprints of Lung Adenocarcinoma

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.751800 ◽

2021 ◽

Vol 9 ◽

Author(s):

Jing Wu ◽

Jiawei Zhou ◽

Qian Xu ◽

Ruth Foley ◽

Jianqiang Guo ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Nk Cell ◽

Prognostic Significance ◽

Predictive Ability ◽

Predictive Biomarker ◽

Tumor Stage ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Key Genes ◽

Immune Related Genes

The identification of reliable indicators in the tumor microenvironment (TME) is critical for tumor prognosis. Tumor associated macrophages (TAMs) are the major component of non-tumor stromal cells in TME and have increasingly been recognized as a predictive biomarker for lung adenocarcinoma (LUAD) prognosis. Here, we report the development of a prognosis model for LUAD using three immune-related genes (IRGs) detected in The Cancer Genome Atlas (TCGA) which potentially regulate TAMs in TME. In 497 LUAD patients, higher immune scores conferred better overall survival (OS). We identified 93 hub IRGs out of 234 for further prognostic significance. Among them, three IRGs (BTK, Cd1c, and S100P) were proved to be closely correlated to the prognosis of patients with LUAD. Moreover, the immune risk score (IRS) based on the gene expression level of the three IRGs was an independent prognostic factor for OS. Higher IRS predicted lower OS, higher mortality and worse tumor stage. With a good predictive ability [area under the ROC curve (AUC) in TCGA = 0.701, AUC in GEO = 0.722], the IRS contributed to a good risk stratification ability of the nomogram. Immunologically, the three IRGs were related to M1 macrophages and NK cell subsets in TME. Interestingly, by characterizing these immune components in situ we found that S100P is a driver for tumor cells to induce TAM migration and M2 polarization in the immunosuppressive tumor niche. We identified the key genes driving TAM migration and transformation and elucidated the immune landscape of LUAD. The data suggest that IRGs from TME have the potential to become indicators for estimating cancer prognosis and guiding individualized treatment.

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Copy number variant heterogeneity among cancer types reflects inconsistent concordance with diagnostic classifications

10.1101/2021.03.01.433348 ◽

2021 ◽

Author(s):

Paula Carrio Cordo ◽

Michael Baudis

Keyword(s):

Copy Number ◽

Genome Instability ◽

Malignant Tumors ◽

Meta Analysis ◽

Copy Number Variant ◽

General Purpose ◽

Classification Systems ◽

Cancer Prognosis ◽

Molecular Characteristics ◽

Data Interoperability

Due to frequent genome instability and accumulation of mutations during the neoplastic process, malignant tumors present with patterns of somatic genome variants on diverse levels of heterogeneity. The delineation of pathophysiological consequences of these patterns remains one of the main challenges in cancer prognosis and treatment. Although continuous efforts aim for better characterization of cancer entities through inclusion of molecular characteristics, current ontology systems still heavily rely on clinico-pathological features. Traditionally, malignant diseases have been classified using domain-specific or generalized classification systems, based on histopathological features and clinical gestalt. Aside from the general purpose 'International Classification for Diseases in Oncology' (ICD-O; WHO), hierarchical terminologies such as NCIt promote data interoperability and ontology-driven computational analysis. To evaluate two prominent, general cancer classification systems (NCIt and ICD-O) towards their concordance with genomic mutation patterns we have performed a data-driven meta-analysis of 83'505 curated cancer samples with genome-wide CNA (copy number aberration) profiles from our Progenetix database. The analysis provides a basis to assess the correspondence level of existing classification systems with respect to homogeneous molecular groups, and how individual codes represent an adequately detailed classification.

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Prognostic significance of LncRNA GHET1 expression in various cancers: a systematic review and meta-analysis

Bioscience Reports ◽

10.1042/bsr20190608 ◽

2019 ◽

Vol 39 (10) ◽

Cited By ~ 3

Author(s):

Jing Ye ◽

Haiyan Sun ◽

Zhengquan Feng ◽

Qiqin Zhang ◽

Yongliang Xia ◽

...

Keyword(s):

Meta Analysis ◽

Clinical Stage ◽

Prognostic Significance ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Advanced Clinical Stage ◽

Human Cancers ◽

Non Coding Rna ◽

Cancer Genome Atlas ◽

Meta Analyses

Abstract Background: Dysregulated expression of long non-coding RNA gastric carcinoma high expressed transcript 1 (lncRNA GHET1) has been observed in several cancers, however, definite conclusion on the prognostic value of lncRNA GHET1 expression in human cancers has not been determined. The aim of this meta-analysis was to evaluate the prognostic significance of lncRNA GHET1 expression in cancers. Methods: PubMed, Web of Science and Embase were comprehensively searched for relevant studies. Meta-analyses of overall survival (OS) and clinicopathological features were conducted. Results: Ten studies were finally analyzed in the present study. High lncRNA GHET1 expression was associated with shorter OS than low lncRNA GHET1 expression in cancers (hazard ratio (HR) = 2.59, 95% CI = 1.93–3.47, P<0.01). Online cross-validation using The Cancer Genome Atlas (TCGA) data observed similar results (HR = 1.10, P<0.05). When compared with low lncRNA GHET1 expression, high lncRNA GHET1 expression was related to larger tumor size (P<0.01), worse differentiation (P<0.01), earlier distant metastasis (P=0.02), earlier lymph node metastasis (P<0.01) and more advanced clinical stage (P<0.01). Conclusion: High lncRNA GHET1 expression is associated with worse cancer prognosis and can serve as a promising prognostic factor of human cancers.

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Does GP training in depression care affect patient outcome? - A systematic review and meta-analysis

BMC Health Services Research ◽

10.1186/1472-6963-12-10 ◽

2012 ◽

Vol 12 (1) ◽

Cited By ~ 43

Author(s):

Claudia Sikorski ◽

Melanie Luppa ◽

Hans-Helmut König ◽

Hendrik van den Bussche ◽

Steffi G Riedel-Heller

Keyword(s):

Patient Outcome ◽

Systematic Review ◽

Meta Analysis ◽

Depression Care ◽

Affect Patient Outcome ◽

Gp Training

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Regulation of the tumor suppressor PLZF and prostate cancer prognosis.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.137 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 137-137

Author(s):

Konrad Hermann Stopsack ◽

Travis A. Gerke ◽

Svitlana Tyekucheva ◽

Lorelei A. Mucci ◽

Philip W. Kantoff

Keyword(s):

Tumor Suppressor ◽

Copy Number ◽

Transcriptome Profiling ◽

Copy Number Variations ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Health Study ◽

Gleason Grade

137 Background: PLZF ( ZBTB16) is an androgen-regulated tumor suppressor gene. Homozygous PLZF deletions are seen in a proportion of localized as well as castration-resistant prostate cancers (PC). Since PTEN has been shown to regulate PLZF expression in vitro, we hypothesized that PTEN status impacts PLZF expression in men with PC. We further hypothesized that low PLZF is associated with a poorer PC prognosis. Methods: We studied patients diagnosed with PC during prospective follow-up of the Health Professionals Follow-up Study (HPFS; n = 254) and the Physicians’ Health Study (PHS; n = 150). We performed whole transcriptome profiling of tumor specimens from cancer diagnosis and, in a subset of patients ( n = 253), a genomically-validated immunohistochemistry for PTEN. Patients were followed for metastases and PC-specific mortality (lethal cancer) after primary treatment for a median of 14 years. Univariable linear and multivariable logistic regression models for cancer outcomes, adjusted for age and calendar year, were used. For validation, the association of PTEN copy number variations and PLZF mRNA expression was assessed in The Cancer Genome Atlas (TCGA) primary PC cohort (n = 333). Results: Loss of PTEN protein expression was associated with lower PLZF expression (–0.72 standard deviations [SD]; 95% CI, –0.38 to –1.06; p < 0.001; HPFS and PHS cohorts), as were copy number variations in PTEN (TCGA cohort; –0.46 SD for deep deletions vs. diploid status; 95% CI, –0.13 to –0.79; p = 0.006) . PLZF expression did not differ significantly by Gleason grade in any cohort (all p > 0.09). In both the HPFS and PHS cohorts, the 25% of patients with the lowest PLZF expression were significantly more likely than those with higher expression to have progression to lethal cancer. This association was independent from Gleason grade, PTEN loss, and a signature of androgen receptor signaling (adjusted odds ratio for lethal cancer, 2.69; 95% CI, 1.18 to 6.14; p = 0.019). Conclusions: Loss of PTEN expression is associated with lower expression of PLZF amongst primary PC not exposed to ADT. In line with its action as a tumor suppressor, low PLZF expression is associated with lethal PC. Whether further suppression of PLZF with ADT worsens outcomes in advanced PC needs further study.

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Prognostic Roles of N6-Methyladenosine METTL3 in Different Cancers: A System Review and Meta-Analysis

Cancer Control ◽

10.1177/1073274821997455 ◽

2021 ◽

Vol 28 ◽

pp. 107327482199745

Author(s):

KuangZheng Liu ◽

Yue Gao ◽

Kai Gan ◽

YuQing Wu ◽

Bin Xu ◽

...

Keyword(s):

Confidence Interval ◽

Odds Ratio ◽

Meta Analysis ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Tumor Biomarker ◽

Cancer Breast ◽

Cancer Genome Atlas ◽

Cancer Types ◽

And Gender

Background: Recent studies have shown that methyltransferase-like 3, a catalytic enzyme that is predominant in the N6-methyladenosine methyltransferase system, is abnormally expressed in various types of carcinoma and is correlated with poorer prognosis. However, the clinical functions of methyltransferase-like 3 in the prognosis of tumors are not fully understood. Methods: We identified studies by searching PubMed, Web of Science, and MedRvix for literature (up to June 30, 2020), and collected a total of 9 studies with 1257 patients for this meta-analysis. The cancer types included gastric cancer, breast cancer, non-small cell lung cancer, bladder cancer, colorectal cancer and ovarian. We further used The Cancer Genome Atlas dataset to validate the results. Results: High methyltransferase-like 3 expression clearly predicted a worse outcome (high vs. low methyltransferase-like 3 expression group; hazard ratio = 2.09, 95% confidence interval 1.53–2.89, P = 0.0001). Moreover, methyltransferase-like 3 expression was associated with differentiation (moderate + poor vs. well, pooled odds ratio = 1.76, 95% confidence interval 1.32–2.35, P = 0.0001), and gender (male vs. female, pooled odds ratio = 0.73, 95% confidence interval 0.55-0.97, P = 0.029). Conclusion: Our results suggest that methyltransferase-like 3 upregulation is significantly associated with poor prognosis and could potentially function as a tumor biomarker in cancer prognosis.

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Prognostic Effect of lncRNA SNHG7 On Cancer Outcome: A Meta and Bioinformatic Analysis

10.21203/rs.3.rs-143840/v1 ◽

2021 ◽

Author(s):

yunyuan zhang ◽

Qingwu Tian ◽

Shifeng Huang ◽

Qing Wang ◽

Hongmei Wu ◽

...

Keyword(s):

Cancer Patients ◽

Prognostic Value ◽

Digestive System ◽

Small Sample Size ◽

Meta Analysis ◽

Tumor Stage ◽

Small Sample ◽

The Cancer Genome Atlas ◽

Significant Heterogeneity ◽

Digestive System Cancer

Abstract Background: New evidence from clinical and fundamental researches suggests that SNHG7 is involved in the occurrence and development of carcinomas. And the increase levels of SNHG7 are associated with poor prognosis in various kinds of tumors. However, the small sample size was the limitation for the prognostic value of SNHG7 in clinical application. The aim of the present meta-analysis was to conduct a qualitative analysis to explore the prognostic value of SNHG7 in various cancers. Methods: Articles related to the SNHG7 as a prognostic biomarker for cancer patients, were comprehensive searched in several electronic databases. The enrolled articles were qualified via the preferred reporting items for systematic reviews and meta-analysis of observational studies in epidemiology checklists. Additionally, an online database based on The Cancer Genome Atlas (TCGA) was further used to validate our results.Results: We analyzed 2418 cancer patients that met the specified criteria. The present research indicated that an elevated SNHG7 expression level was significantly associated with unfavorable overall survival (OS) (HR = 2.45, 95% CI: 2.12–2.85, p <0.001). Subgroup analysis showed that high expression levels of SNHG7 were also significantly associated with unfavorable OS in digestive system cancer (HR = 2.31, 95% CI: 1.90–2.80, p <0.001) and non-digestive system cancer (HR = 2.67, 95% CI: 2.12–3.37, p <0.001). Additionally, increased SNHG7 expression was found to be associated with tumor stage and progression (III/IV vs. I/II: HR = 1.76, 95% CI: 1.57–1.98, p <0.001). Furthermore, elevated SNHG7 expression significantly predicted lymph node metastasis (LNM) (HR = 1.98, 95% CI: 1.74–2.26, p <0.001) and distant metastasis (DM) (HR = 2.49, 95% CI: 1.88–3.30, p <0.001) respectively. No significant heterogeneity was observed among these studies. SNHG7 was significantly upregulated in four cancers and the elevated expression of SNHG7 predicted shorter OS in four malignancies and worse DFS in five malignancies based on the validation using the GEPIA cohort.Conclusions: The present analysis suggests that elevated SNHG7 is significantly associated with unfavorable OS, tumor progression, LNM and DM in various carcinomas, and may be used as a promising biomarker to guide therapy for cancer patients.

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The Clinical Prognostic Value of lncRNA SBF2-AS1 in Cancer Patients: A Meta-Analysis

Technology in Cancer Research & Treatment ◽

10.1177/15330338211004915 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110049

Author(s):

Jie Wang ◽

Pingyong Zhong ◽

Hao Hua

Keyword(s):

Cancer Patients ◽

Histological Grade ◽

Meta Analysis ◽

The Cancer Genome Atlas ◽

Cancer Prognosis ◽

Cochrane Library ◽

Patients With Cancer ◽

Hazard Ratios ◽

Non Coding Rna ◽

Tcga Dataset

Background: The mortality and recurrence of patients with cancer is of high prevalence. SET-binding factor 2 (SBF2) antisense RNA1 (lncRNA-SBF2-AS1) is a promising long non-coding RNA. There is increasing evidence that SBF2-AS1 is abnormally expressed in various tumors and is associated with cancer prognosis. However, the identification of the effect of lncRNA SBF2-AS1 in tumors remains necessary. Materials and Methods: Up to November 2, 2020, electronic databases, including PubMed, Cochrane Library, EMBASE, Medline, and Web of Science, were searched. The results were evaluated by pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs). Results: A total of 11 literatures on cancer patients were included for the present meta-analysis. The combined results revealed that high expression of SBF2-AS1 was significantly associated with unfavorable overall survival (OS) (HR = 1.48, 95% CI: 1.34-1.62, P < 0.00001) in a variety of cancers. In additional, the increase in SBF2-AS1 expression was also correlated with tumor size ((larger vs. smaller) OR = 2.34, 95% CI: 1.47-3.70, P = 0.0003), advanced TNM stage ((III/IV vs. I/II) OR = 2.78, 95% CI: 1.75-4.41, P < 0.0001), lymph node metastasis ((Positive vs. Negative) OR = 3.06, 95% CI: 1.93-4.86, P < 0.00001), and histological grade ((poorly vs. well/moderately) OR = 2.58, 95% CI: 1.47-4.52, P = 0.001) in patients with cancer. Furthermore, The Cancer Genome Atlas (TCGA) dataset valuated that SBF2-AS1 was upregulated in a variety of tumors, and predicted the worse prognosis. Conclusions: Our results of this meta-analysis demonstrate that high SBF2-AS1 expression may become a potential target for predicting the prognosis of human cancers.

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