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Prognostic Value of CD44 and Its Isoforms in Advanced Cancer: A Systematic Meta-Analysis With Trial Sequential Analysis.

ABSTRACT: Objective: Cancer stem cell marker CD44 and its variant isoforms (CD44v) may be correlated with tumor growth, metastasis, and chemo-radiotherapy resistance. However, the prognostic power of CD44 and CD44v in advanced cancer remains controversial. Therefore, the purpose of our study was to generalize the prognostic significance of these cancer stem cell markers in advanced cancer patients. Methods: Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated from multivariable analysis to assess the associations among CD44, CD44v6, and CD44v9 positivity and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), and recurrence-free survival (RFS). Trial sequential analysis (TSA) was also conducted. Results: We included 15 articles that reported on 1,201 patients with advanced cancer (CD44: nine studies with 796 cases, CD44v6: three studies with 143 cases, and CD44v9: three studies with 262 cases). CD44 expression was slightly linked to worse OS (HR = 2.03, P = 0.027), but there was no correlation between CD44 expression and DFS, RFS, or PFS. Stratified analysis showed that CD44 expression was not correlated with OS at ?5 years or OS in patients receiving adjuvant therapy. CD44v6 expression was not associated with OS. CD44v9 expression was closely associated with poor 5-years CSS in patients treated with chemo/radiotherapy (HR = 3.62, P < 0.001). However, TSA suggested that additional trials were needed to confirm these conclusions. Conclusions: CD44 or CD44v9 might be novel therapeutic targets for improving the treatment of advanced cancer patients. Additional prospective clinical trials are strongly needed across different cancer types.

SUBMITTER: Han S

PROVIDER: S-EPMC6372530 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Project description:Simple Summary Head and neck squamous cell carcinoma (HNSCC) is the neoplasm with the highest incidence in the head and neck regions. More than 350,000 new cases of carcinoma are diagnosed worldwide every year, but the prognosis has not improved significantly in the past few decades. In addition to smoking and alcohol habits, which represent the main risk factors for HNSCC, deregulation of non-coding RNAs have been identified as negative prognostic survival factors. The expression of miR-155 appears to be altered in many neoplasms and its different expression in tumor tissues can represent a prognostic biomarker of survival. By carrying out a systematic review and meta-analysis of the data in the current international literature, we aim to provide the most up-to-date data on the different expression miR-155 and to correlate those data with the prognostic indices of survival in HNSCC. Abstract Head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers worldwide; in fact, it is among the top six neoplasms, with an incidence of about 370,000 new cases per year. The 5-year survival rate, despite chemotherapy, radiotherapy, and surgery for stages 3 and 4 of the disease, is low. MicroRNAs (miRNAs) are a large group of small single-stranded non-coding endogenous RNAs, approximately 18–25 nucleotides in length, that play a significant role in the post-transcriptional regulation of genes. Recent studies investigated the tissue expression of miR-155 as a prognostic biomarker of survival in HNSCC. The purpose of this systematic review is, therefore, to investigate and summarize the current findings in the literature concerning the potential prognostic expression of tissue miR-155 in patients with HNSCC. The revision was performed according to PRISMA indications: three databases (PubMed, Scopus, and the Cochrane Register) were consulted through the use of keywords relevant to the revision topic. Totally, eight studies were included and meta-analyzed. The main results report for the aggregate HR values of 1.40 for OS, 1.36 for DFS, and 1.09 for DPS. Finally, a trial sequencing analysis was also conducted to test the robustness of the proposed meta-analysis.

Project description:IntroductionBreathlessness in advanced cancer, a frequent multicomponent and debilitating disorder, severely reduces function and quality of patients' life. Multiple studies have shown that non-pharmacological therapies can effectively palliate breathlessness in advanced cancer. However, no systematic review has investigated the application of acupuncture, as a non-pharmacological treatment, for breathlessness in advanced cancer. A systematic review will be conducted to summarise evidence supporting the efficacy and safety of acupuncture as a therapeutic option for breathlessness in advanced cancer based on existing randomised controlled trials (RCTs).MethodsRCTs will be retrieved from nine scientific databases, including the MEDLINE via PubMed, Web of Science via the Web of Knowledge, Embase via Ovid, the Cochrane Central Register of Controlled Trials via the Cochrane Library, and Allied and Complementary Medicine Database via EBSCO, China National Knowledge Infrastructure, Wanfang Database, VIP Database, Chinese Biomedical Literature Database; three clinical registry platforms, including the WHO International Clinical Trials Registry Platform, NIH Clinical trials.gov and Chinese Clinical Trial Registry, as well as from other sources. Studies published since inception of these databases to 1 August 2021 will be retrieved. Search terms will include breathlessness, cancer, acupuncture and RCT. Two investigators will independently select and extract data from RCTs and assess the risk of bias. The primary outcome, which is alleviation of breathlessness, will be assessed. Meta-analysis will be performed using RevMan V.5.4 and STATA V.15.0. The TSA 0.9.5.10 β software will be used to conduct trial sequential analysis. Finally, the quality of evidence from RCTs will be assessed using the Grading of Recommendations Assessment, Development and Evaluation System tool.Ethics and disseminationResults will be disseminated through peer-reviewed journals or conference reports. Since this study involves acquisition of secondary data, ethical approval requirements will be waived.Prospero registration numberCRD42021240085.

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Prognostic Value of CD44 and Its Isoforms in Advanced Cancer: A Systematic Meta-Analysis With Trial Sequential Analysis.

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