scholarly journals Deep analysis of neuroblastoma core regulatory circuitries using online databases and integrated bioinformatics shows their pan-cancer roles as prognostic predictors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Leila Jahangiri ◽  
Perla Pucci ◽  
Tala Ishola ◽  
Joao Pereira ◽  
Megan L. Cavanagh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Patient Survival ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Deep Understanding ◽  
Risk Groups ◽  
Tumour Microenvironment ◽  
Cancer Prognosis ◽  
Human Pathology ◽  
Pan Cancer

Abstract Aim Neuroblastoma is a heterogeneous childhood cancer derived from the neural crest. The dual cell identities of neuroblastoma include Mesenchymal (MES) and Adrenergic (ADRN). These identities are conferred by a small set of tightly-regulated transcription factors (TFs) binding super enhancers, collectively forming core regulatory circuitries (CRCs). The purpose of this study was to gain a deep understanding of the role of MES and ADRN TFs in neuroblastoma and other cancers as potential indicators of disease prognosis, progression, and relapse. Methods To that end, we first investigated the expression and mutational profile of MES and ADRN TFs in neuroblastoma. Moreover, we established their correlation with neuroblastoma risk groups and overall survival while establishing their extended networks with long non-coding RNAs (lncRNAs). Furthermore, we analysed the pan-cancer expression and mutational profile of these TFs and their correlation with patient survival and finally their network connectivity, using a panel of bioinformatic tools including GEPIA2, human pathology atlas, TIMER2, Omicsnet, and Cytoscape. Results We show the association of multiple MES and ADRN TFs with neuroblastoma risk groups and overall survival and find significantly higher expression of various MES and ADRN TFs compared to normal tissues and their association with overall survival and disease-free survival in multiple cancers. Moreover, we report the strong correlation of the expression of these TFs with the infiltration of stromal and immune cells in the tumour microenvironment and with stemness and metastasis-related genes. Furthermore, we reveal extended pan-cancer networks comprising these TFs that influence the tumour microenvironment and metastasis and may be useful indicators of cancer prognosis and patient survival. Conclusion Our meta-analysis shows the significance of MES and ADRN TFs as indicators of patient prognosis and the putative utility of these TFs as potential novel biomarkers.

scholarly journals Prognostic Value of MicroRNA-497 in Various Cancers: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Zhiqiang Liu ◽  
Shanshan Wu ◽  
Lei Wang ◽  
Shuling Kang ◽  
Bixing Zhao ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Biomarker ◽  
Data Extraction ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Cancer Prognosis ◽  
Cancer Type ◽  
Free Survival ◽  
Knowledge Infrastructure ◽  
Hazard Ratios

Background. Some studies showed that microRNA-497 (miR-497) might act as a prognostic biomarker of cancer. However, the conclusion was not consistent. The aim of this study was to investigate the prognostic role of miR-497 in various carcinomas. Methods. We systematically searched the databases of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Data to identify relevant studies. Two independent reviewers performed the data extraction and assessed the study quality. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for overall survival (OS) and disease-free survival/relapse-free survival (DFS/RFS) were used to assess the associations between miR-497 expression and cancer prognosis. Results. A total of 15 studies involving 1760 participants fulfilled the inclusion criteria. The lower level of miR-497 expression was significantly associated with shorter overall survival (HR=2.19, 95% CI: 1.84-2.60). No significant association was found between miR-497 expression and DFS/RFS in various carcinomas (HR=1.17, 95% CI: 0.53-2.57). Subgroup analyses by ethnicity and cancer type showed the consistent results. Conclusion. Our studies suggested that miR-497 might be a prognostic biomarker in cancers. However, further multicenter prospective clinical researches are needed to confirm the association between miR-497 expression and cancer prognosis.

Prognostic role of tumor-inflating lymphocytes in gastric cancer: A systematic review and meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15578-e15578
Author(s):  
Der Sheng Sun ◽  
Jung Soo Lee ◽  
Soon Auck Hong ◽  
Hye Sung Won ◽  
Yoon Ho Ko
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Survival Data ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Foxp3 Expression ◽  
Survival Outcome ◽  
Cancer Prognosis ◽  
Infiltrating Lymphocytes

e15578 Background: Tumor-infiltrating lymphocytes(TILs) may act as major determinants of the host immune response to tumor cells. However, the potential prognostic value of TILs in gastric cancer remains controversial. This meta-analysis analyzed the associations between TILs and survival outcomes in gastric cancer. Methods: Eligible 24 published studies were identified by searching the PubMed and Google scholar databases. The primary clinical outcome was defined as overall survival (OS) or disease-free survival (DFS), which were analyzed by subgroups such as TILs subtype. The total of the study sample sizes in eligible 24 published studies was 3,229, which ranged from 52 to 273 (median, 120) patients. All studies were non-randomized and retrospective study. The only multivariate hazard ratio(HR) among patient survival data were pooled, and pooled multivariate HR with 95% confidence intervals (95% CI) were used to calculate the strength of this association between TILs expression and survival outcome. Results: The pooled multivariate hazard ratios suggested that high expression of TILs was associated with better overall survival outcome (pooled HR = 0.69, 95% CI 0.57–0.82), compared to low TILs expression in twenty-three eligible studies, particularly in CD8(+) lymphocytes (pooled HR = 0.63, 95% CI 0.48 –0.83). In contrast, a pooled analysis of the FOXP3 (+) T cells or Treg subgroup showed that high FOXP3 (+) expression was negatively correlated with OS (pooled HR = 1.88, 95% CI 1.34 –2.63). In an analysis of seven studies on DFS, the infiltration by TILs, CD4(+) or CD8(+) lymphocytes (pooled HR = 0.59, 95% CI 0.42 –0.81), not by the infiltration of FOXP3 (+) T lymphocytes (pooled HR = 1.82, 95% CI 1.30 – 2.53), was significantly associated with better survival outcome. Conclusions: The results from this meta-analysis suggest that TILs and TILs subsets expression can be a potential prognostic biomarker in patients with gastric cancer. Key Words: Tumor-infiltrating lymphocytes, gastric cancer, prognosis, meta-analysis

scholarly journals HOTAIR as a Prognostic Predictor for Diverse Human Cancers: A Meta- and Bioinformatics Analysis

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 778 ◽  
Author(s):  
Halil Ibrahim Toy ◽  
Didem Okmen ◽  
Panagiota I. Kontou ◽  
Alexandros G. Georgakilas ◽  
Athanasia Pavlopoulou
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Bioinformatics Analysis ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Free Survival ◽  
Human Cancers ◽  
Potential Biomarker

Several studies suggest that upregulated expression of the long non-coding RNA HOX transcript antisense RNA (HOTAIR) is a negative predictive biomarker for numerous cancers. Herein, we performed a meta-analysis to further investigate the prognostic value of HOTAIR expression in diverse human cancers. To this end, a systematic literature review was conducted in order to select scientific studies relevant to the association between HOTAIR expression and clinical outcomes, including overall survival (OS), recurrence-free survival (RFS)/disease-free survival (DFS), and progression-free survival (PFS)/metastasis-free survival (MFS) of cancer patients. Collectively, 53 eligible studies including a total of 4873 patients were enrolled in the current meta-analysis. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were calculated to assess the relationship between HOTAIR and cancer patients’ survival. Elevated HOTAIR expression was found to be significantly associated with OS, RFS/DFS and PFS/MFS in diverse types of cancers. These findings were also corroborated by the results of bioinformatics analysis on overall survival. Therefore, based on our findings, HOTAIR could serve as a potential biomarker for the prediction of cancer patient survival in many different types of human cancers.

scholarly journals Pan-cancer systematic identification of lncRNAs associated with cancer prognosis

2018 ◽  
Author(s):  
Matthew H. Ung ◽  
Evelien Schaafsma ◽  
Daniel E. Mattox ◽  
George L. Wang ◽  
Chao Cheng
Keyword(s):  
Drug Targets ◽  
Patient Survival ◽  
Cancer Prognosis ◽  
Rna Seq ◽  
Non Coding Rna ◽  
Cancer Types ◽  
Microarray Studies ◽  
Systematic Identification ◽  
Pan Cancer ◽  
Novel Associations

AbstractThe “dark matter” of the genome harbors several non-coding RNA species including IncRNAs, which have been implicated in neoplasias but remain understudied. RNA-seq has provided deep insights into the nature of lncRNAs in cancer but current RNA-seq data are rarely accompanied by longitudinal patient survival information. In contrast, a plethora of microarray studies have collected these clinical metadata that can be leveraged to identify novel associations between gene expression and clinical phenotypes. In this study, we developed an analysis framework that computationally integrates RNA-seq and microarray data to systematically screen 9,463 lncRNAs for association with mortality risk across 20 cancer types. In total, we identified a comprehensive list of associations between lncRNAs and patient survival and demonstrate that these prognostic lncRNAs are under selective pressure and may be functional. Our results provide valuable insights that facilitate further exploration of lncRNAs and their potential as cancer biomarkers and drug targets.

scholarly journals Prognostic Value of Long Noncoding RNA NORAD in Various cancers: a meta-analysis

2020 ◽  
Author(s):  
Qin Yang ◽  
Zheng Zhang ◽  
Yuan-Yuan Gong ◽  
Zhi-Ran Li ◽  
Hua-Zhu Zhang ◽  
...  
Keyword(s):  
Risk Factor ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Bioinformatics Analysis ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Cancer Prognosis ◽  
Clinicopathological Parameters ◽  
Survival Outcomes ◽  
Free Survival

Abstract Objective: Accumulating studies reported that noncoding RNA activated by DNA damage (NORAD) was correlated with poor survival outcomes for patients in different cancers. However, the effects of NORAD on cancer prognosis were controversial. Therefore, a meta-analysis was carried out to elucidate this issue. Methods: Literature search was performed to collect eligible relevant publications until June 2020. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association of NORAD with prognosis and clinical features in diverse cancers. In addition, bioinformatics analysis was also utilized to validate the results of the meta-analysis. Results: Fourteen relevant articles involving 867 patients were enrolled in the present study. The pooled results showed that elevated expression of NORAD was a risk factor for overall survival (HR = 1.46, 95% CI: 1.06-2.01, P = 0.020), disease-free survival (HR = 1.74, 95% CI: 1.18-2.57, P = 0.005) and recurrence-free survival. Besides, overexpression of NORAD significantly correlated with lymph node metastasis and T stage. Additionally, bioinformatics analysis further strengthened and complemented the results of the present study. Conclusion: Our results showed that NORAD was a risk factor for survival outcomes and clinicopathological parameters in cancer patients. These findings indicated that NORAD may be a promising candidate for prognosis prediction and potential therapeutic target in diverse cancers. Key words: Long noncoding RNA, NORAD, prognosis, cancer, meta-analysis

Predictive Prognostic Value of Tissue-Based MicroRNA Expression in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-analysis

2018 ◽  
Vol 97 (7) ◽  
pp. 759-766 ◽  
Author(s):  
G. Troiano ◽  
F. Mastrangelo ◽  
V.C.A. Caponio ◽  
L. Laino ◽  
N. Cirillo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Mirna Expression ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

Oral squamous cell carcinoma (OSCC) is a common type of cancer characterized by a low survival rate, mostly due to local recurrence and metastasis. In view of the importance of predicting tumor behavior in the choice of treatment strategies for OSCC, several studies have attempted to investigate the prognostic value of tissue biomarkers, including microRNA (miRNA). The purpose of this study was to perform a systematic review and meta-analysis to evaluate the relationship between miRNA expression and survival of OSCC patients. Studies were identified by searching on MEDLINE/PubMed, SCOPUS, Web of Science, and Google Scholar. Quality assessment of studies was performed with the Newcastle-Ottawa Scale. Data were collected from cohort studies comparing disease-free survival and overall survival in patients with high miRNA expression compared to those with low expression. A total of 15 studies featuring 1,200 OSCC samples, predominantly from Asia, met the inclusion criteria and were included in the meta-analysis. Poor prognosis correlated with upregulation of 9 miRNAs (miR-21, miR-455-5p, miiR-155-5p, miR-372, miR-373, miR-29b, miR-1246, miR-196a, and miR-181) and downregulation of 7 miRNAs (miR-204, miR-101, miR-32, miR-20a, miR-16, miR-17, and miR-125b). The pooled hazard ratio values (95% confidence interval) related to different miRNA expression for overall survival and disease-free survival were 2.65 (2.07–3.39) and 1.95 (1.28–2.98), respectively. The results of this meta-analysis revealed that the expression levels of specific miRNAs can robustly predict prognosis of OSCC patients.

TP1.2.3Oncological Outcomes of Organ Preservation Strategies - Local Excision Procedures and ‘Watchful Waiting’ In Management of Low Rectal Cancers – A Systematic Review And Meta-Analysis

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
A R Aspari ◽  
V Ramesh ◽  
G Kumar ◽  
S N Narayanasamy ◽  
A O Gumber ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Local Recurrence ◽  
Organ Preservation ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Free Survival ◽  
Rectal Cancers ◽  
Disease Free

Abstract Objective To evaluate local recurrence, metastases, and survival outcomes of `wait and watch’ (WW) strategy and local excision (LE) of tumours, in comparison to the present standard practice of total mesorectal excision (TME) for locally advanced rectal cancers. Data Sources MEDLINE, EMBASE, PubMed databases, and sources of Grey literature. Study Selection Randomised and non-randomised prospective studies, retrospective studies with propensity-score-matched analyses. Data Extraction and Synthesis These were carried out independently by two reviewers. A random-effects methodology was used for meta-analyses. Data was presented keeping with the 27-item PRISMA checklist. Main Outcomes The primary outcomes of interest were local recurrence, distant metastases, disease-free-survival and overall-survival, which were assessed in comparison to those associated with radical surgeries (TME). Results 7 of the 16 studies in the systematic review were included for the quantitative synthesis and meta-analysis. Local recurrence rates were comparable amongst patients in WW group and LE group to those undergoing TME. [Risk ratio (RR) 3.07/1.41; 95% Confidence Interval (CI) 0.86-10.95/0.66-3.01; P = 0.08/P=0.89 respectively]. Rates of distant metastases in the WW group and LE group were comparable to those undergoing TME [RR = 0.71/0.94; 95% CI 0.22-2.30/0.55-1.61; P = 0.56/ P = 0.83 respectively]. The median 3-year disease-free survival among patients undergoing WW, LE procedure, and TME were 88%, 80%, and 78.2% respectively; and the median 3-year overall survival among the three groups were 96%, 93%, and 89.5% respectively. Conclusions and Relevance Organ-preservation strategies appear to be a viable treatment option in the management of rectal-cancers. Further research is warranted to provide stronger levels of evidence on organ-preservation strategies.

Lobar versus Sublobar Resection in the Elderly for Early Lung Cancer: A Meta-Analysis

2021 ◽  
Author(s):  
Josiah Ng ◽  
Yoshio Masuda ◽  
Jun Jie Ng ◽  
Lowell Leow ◽  
Andrew M. T. L. Choong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Meta Analysis ◽  
Cancer Recurrence ◽  
Disease Free Survival ◽  
The Elderly ◽  
Sublobar Resection ◽  
Cell Lung Carcinoma ◽  
Risk Of Death ◽  
Stage 1

Abstract Objectives We performed a systematic review and meta-analysis of outcomes of lobectomy versus sublobar resection in elderly patients (≥65) with stage 1 nonsmall cell lung carcinoma (NSCLC). Methods We searched for relevant articles using a set of inclusion and exclusion criteria. Meta-analytic techniques were applied. Results Twelve studies (n = 5834) were chosen. Our results indicate that in the elderly, lobectomy for stage 1 NSCLC confers a survival advantage over sublobar resection. Lobectomy patients had a lower risk of death within 5 years and lower odds of local cancer recurrence. Our results show that lobectomy had a better 5-year cancer-specific survival and 5-year disease-free survival that trended toward significance. The sublobar resection group showed better 30-day operative mortality that trended toward significance. Subgroup analysis of stage 1A cancer demonstrated no difference in 5-year overall survival rates. However, for stage 1B tumors 5-year overall survival favored lobectomy. Conclusion Lobectomy for stage 1 NSCLC in elderly patients is superior to sublobar resection in terms of survival and cancer recurrence and should be afforded where possible. For stage 1A tumors, sublobar resection is noninferior and may be considered. Further randomized controlled trials in this topic is required.

Postoperative PET/CT for detection of early recurrence (ER) after surgery for squamous cell carcinomas (SCC) of the oral cavity (OC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6060-6060
Author(s):  
Yao Yu ◽  
Heiko Schöder ◽  
Jung Kang ◽  
Sean Matthew McBride ◽  
C. Jillian Tsai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
High Risk ◽  
Postoperative Radiotherapy ◽  
Prospective Trial ◽  
Disease Free Survival ◽  
Distant Metastases ◽  
Risk Groups ◽  
Free Survival ◽  
Pet Ct

6060 Background: Patients with ER after surgery and prior to postoperative radiation (RT) for SCC of the OC have aggressive biology and poor prognosis. After the introduction of a PET/CT simulator in our department, we incorporated post-operative PET/CT as part of RT planning. We hypothesized PET/CT would improve detection of macroscopic disease before postoperative RT. Methods: We reviewed the medical records of patients treated with postoperative radiotherapy between 2005 and 2019 for OC SCC. Clinicopathologic risk factors were recorded. Intermediate risk factors (IRFs) included pT3-4 disease, nodal disease, perineural invasion (PNI), lymphovascular invasion (LVI), and close ( < 5mm) surgical margins (SM); extranodal extension (ENE) and positive SM were considered high-risk factors (HRF). Patients were stratified into risk groups based upon the number and type of risk factors: 0-1 IRFs, 2 IRFs, ≥3 IRFs, and any HRF. Patients were considered to have ER if they had biopsy confirmed recurrence, or if the imaging or exam was sufficiently suspicious, after discussion with the head and neck team, to warrant treatment to definitive doses of RT (70 Gy). Results: Our cohort included 391 patients with SCC of the OCC who were treated with postoperative radiotherapy. 61% of patients were male, 35% had pT3-4 disease, 36% had pN2a-3 disease, 53% had PNI, 20% had LVI, 30% had ENE, and 14% had positive SM. The most common sites were oral tongue (46%), alveolar ridge (18%), and buccal mucosa (13%). 237 (61%) patients underwent postoperative PET/CT planning, and 165 patients (41%) were planned with CT only. Patients screened with post-operative PET/CT were more likely to be diagnosed with ER (46/237, 19.4%) than those simulated with CT only (6/154, 3.9%, p < 0.0001). Among patients simulated with PET/CT, 7%, 9%, 14%, and 35% of patients were diagnosed with ER for patients with 0-1 IRFs, 2 IRFs, ≥3 IRFs, and any HRF, respectively. Median follow-up was 4.1 years (95% CI 3.6 – 4.5). Among 52 patients with ER, 24 (49.0%) had local, 41 (83.7%) had regional, and 5 (10.2%) had distant recurrence. 17 (33%) of ER were biopsy proven. For patients with ER, 3-year freedom from locoregional recurrence, distant-metastasis free survival, and overall survival were 45.2% (95% CI 32% - 64%), 55% (95% CI 42% – 72%), and 43% (95% CI 30% - 61%), respectively. For patients without ER, use of postoperative PET/CT was associated with improved disease-free survival (HR 0.68, 95% CI 0.46 – 0.98, p = 0.041) and overall survival (HR 0.59, 95% CI 0.38 – 0.91, p = 0.019). Conclusions: Postoperative PET/CT may increase detection ER compared to CT simulation alone and improve risk stratification. Patients with ER are at high risk of locoregional failure, distant metastases, and mortality, despite salvage therapy. A prospective trial is underway at our institution to systemically study the role of PET/CT for detection of ER.

scholarly journals Prognostic and clinicopathological significance of pretreatment mean platelet volume in cancer: a meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e037614
Author(s):  
Xin Chen ◽  
Jing Li ◽  
Xunlei Zhang ◽  
Yushan Liu ◽  
Jindong Wu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mean Platelet Volume ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Clinicopathological Parameters ◽  
Platelet Volume ◽  
Poor Overall Survival ◽  
Patients With Cancer ◽  
Clinicopathological Significance

ObjectiveOur study aimed to evaluate the prognostic and clinicopathological significance of pretreatment mean platelet volume (MPV) on cancer by using meta-analysis of published studies.DesignMeta-analysis.Data sourcesRelevant studies available before 22 December 2019 were identified by searching MEDLINE, EMBASE.Eligibility criteriaAll published studies that assessed the prognostic and clinicopathological significance of pretreatment MPV on cancer were included.Data extraction and synthesisStudies were identified and extracted by two reviewers independently. The HR/OR and its 95% CIs of survival outcomes and clinicopathological parameters were calculated.ResultsA total of 38 eligible studies (41 subsets) with 9894 patients with cancer were included in the final meta-analysis. MPV level was not significantly associated with both overall survival (HR 0.98, 95% CI 0.84 to 1.14) and disease-free survival (HR 1.22, 95% CI 0.86 to 1.73) of patients with cancer. Neither advanced nor mixed-stage tumour patients showed significant association between MPV and overall survival (HR 1.36, 95% CI 0.96 to 1.94, HR 0.90, 95% CI 0.74 to 1.09). However, high MPV had the strongest relationship with poor overall survival (HR 2.01; 95% CI 1.08 to 3.41) in gastric cancer, followed by pancreatic cancer (HR 1.54; 95% CI 1.31 to 1.82). Whereas in the subgroup using receiver operating characteristic curve method to define cut-off values, low MPV was significantly related to poor overall survival (HR 0.78, 95% CI 0.64 to 0.95). In addition, MPV had no significant association with age (OR 0.96, 95% CI 0.90 to 1.02), sex (OR 1.04, 95% CI 1.00 to 1.09), depth of cancer invasion (OR 0.90, 95% CI 0.77 to 1.04) and tumour stage (OR 0.91, 95% CI 0.78 to 1.07).ConclusionsPretreatment MPV level is of no clearly prognostic significance in cancers and no significant association with clinicopathological parameters of patients with cancers.

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