Do statins improve outcomes for patients with non-small cell lung cancer? A systematic review and meta-analysis protocol

Introduction Lung cancer is the most common neoplasm and the leading cause of cancer-related death worldwide. Non-small cell lung cancer (NSCLC), accounting for 85% of all lung cancer cases, is frequently diagnosed at an advanced and metastatic stage. In addition, survival of patients with NSCLC has not improved significantly over the recent decades. Statins are used as a cholesterol-lowering agent, but recently preclinical and clinical studies have revealed their anticancer effects. Thus, this systematic review and meta-analysis aims to clarify whether statins improve the prognosis of patients with NSCLC. Methods and analysis We will search MEDLINE (PubMed), EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov with no restriction on language. Both randomised controlled trials (RCTs) and observational cohort studies evaluating the prognostic role of statins in patients with NSCLC will be included. The primary outcome will be overall survival, and the secondary outcomes will include cancer-specific survival, disease-free survival and cancer recurrence. Two assessors will assess the RCTs using the Cochrane Collaboration's risk of bias tool and the observational cohort studies according to ROBINS-I. Publication bias will be assessed by funnel plot using the STATA software v.13.1. Ethics and dissemination No ethical issues are predicted. This systematic review and meta-analysis aims to describe the prognostic effects of statins in patients with NSCLC, which would help clinicians to optimise treatment for patients with NSCLC. These findings will be published in a peer-reviewed journal and presented at national and international conferences. PROSPERO registration number CRD42016047524

Predictive and Prognostic Value of Non-Coding RNA in Breast Cancer

For decades since the central dogma, cancer biology research has been focusing on the involvement of genes encoding proteins. It has been not until more recent times that a new molecular class has been discovered, named non-coding RNA (ncRNA), which has been shown to play crucial roles in shaping the activity of cells. An extraordinary number of studies has shown that ncRNAs represent an extensive and prevalent group of RNAs, including both oncogenic or tumor suppressive molecules. Henceforth, various clinical trials involving ncRNAs as extraordinary biomarkers or therapies have started to emerge. In this review, we will focus on the prognostic and diagnostic role of ncRNAs for breast cancer

Development and Validation of a Prognostic Signature for Malignant Pleural Mesothelioma

Introduction: Dysregulated genes play a critical role in the development and progression of cancer, suggesting their potential as novel independent biomarkers for cancer diagnosis and prognosis. Prognostic model-based gene expression profiles are not widely utilized in clinical medicine. We investigated the prognostic significance of an expression profile-based gene signature for outcome prediction in patients with malignant pleural mesothelioma (MPM).Methods: The gene expression profiles of a large cohort of patients with MPM were obtained and analyzed by repurposing publicly available microarray data. A gene-based risk score model was developed with the training dataset and then validated with the TCGA-MESO (mesothelioma) dataset. The time-dependent receiver operating characteristic (ROC) curve was used to evaluate the prognostic performance of survival prediction. The biological function of the prognostic genes was predicted using bioinformatics analysis.Results: Three genes in the training dataset (GSE2549) were identified as significantly associated with the overall survival (OS) of patients with MPM and were combined to develop a three-gene prognostic signature to stratify patients into low-risk and high-risk groups. The MPM patients of the training dataset in the low-risk group exhibited longer OS than those in the high-risk group (HR = 0.25, 95% CI = 0.11–0.56, P < 0.001). Similar prognostic values for the three-gene signature were observed in the validated TCGA-MESO cohort (HR = 0.53 95% CI = 0.33–0.85, P = 0.008). ROC analysis also demonstrated the good performance in predicting 3-year OS in the GEO and TCGA cohorts (KM-AUC for GEO = 0.989, KM-AUC for TCGA = 0.618). The C-statistic for the 3-gene model was 0.761. Validation with TCGA-MESO confirmed the model's ability to discriminate between risk groups in an alternative data set with fair performance (C-statistic: 0.68). Functional enrichment analysis suggested that these three genes may be involved in genetic and epigenetic events with known links to MPM.Conclusions: This study has identified and validated a novel 3-gene model to reliably discriminate patients at high and low risk of death in unselected populations of patients with MPM. Further larger, prospective multi-institutional cohort studies are necessary to validate this model

CTLA-4 in Regulatory T Cells for Cancer Immunotherapy

Immune checkpoint inhibitors (ICIs) have obtained durable responses in many cancers, making it possible to foresee their potential in improving the health of cancer patients. However, immunotherapies are currently limited to a minority of patients and there is a need to develop a better understanding of the basic molecular mechanisms and functions of pivotal immune regulatory molecules. Immune checkpoint cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and regulatory T (Treg) cells play pivotal roles in hindering the anticancer immunity. Treg cells suppress antigenpresenting cells (APCs) by depleting immune stimulating cytokines, producing immunosuppressive cytokines and constitutively expressing CTLA-4. CTLA-4 molecules bind to CD80 and CD86 with a higher affinity than CD28 and act as competitive inhibitors of CD28 in APCs. The purpose of this review is to summarize state-of-the-art understanding of the molecular mechanisms underlining CTLA-4 immune regulation and the correlation of the ICI response with CTLA-4 expression in Treg cells from preclinical and clinical studies for possibly improving CTLA-4-based immunotherapies, while highlighting the knowledge gap

The Role of Genomics and Proteomics in Lung Cancer Early Detection and Treatment

Lung cancer is the leading cause of cancer-related death worldwide, with non-small-cell lung cancer (NSCLC) being the primary type. Unfortunately, it is often diagnosed at advanced stages, when therapy leaves patients with a dismal prognosis. Despite the advances in genomics and proteomics in the past decade, leading to progress in developing tools for early diagnosis, targeted therapies have shown promising results; however, the 5-year survival of NSCLC patients is only about 15%. Low-dose computed tomography or chest X-ray are the main types of screening tools. Lung cancer patients without specific, actionable mutations are currently treated with conventional therapies, such as platinum-based chemotherapy; however, resistances and relapses often occur in these patients. More noninvasive, inexpensive, and safer diagnostic methods based on novel biomarkers for NSCLC are of paramount importance. In the current review, we summarize genomic and proteomic biomarkers utilized for the early detection and treatment of NSCLC. We further discuss future opportunities to improve biomarkers for early detection and the effective treatment of NSCLC

Antimicrobial Peptides As Biologic and Immunotherapeutic Agents against Cancer: A Comprehensive Overview

Antimicrobial peptides (AMPs) are a pervasive and evolutionarily ancient component of innate host defense which is present in virtually all classes of life. In recent years, evidence has accumulated that parallel or de novo mechanisms by which AMPs curb infectious pathologies are also effective at restraining cancer cell proliferation and dissemination, and have consequently stimulated significant interest in their deployment as novel biologic and immunotherapeutic agents against human malignancies. In this review, we explicate the biochemical underpinnings of their tumor-selectivity, and discuss results of recent clinical trials (outside of oncologic indications) which substantiate their safety and tolerability profiles. Next, we present evidence for their preclinical antitumor activity, systematically organized by the major and minor classes of natural AMPs. Finally, we discuss the barriers to their clinical implementation and envision directions for further development

p53 Antibodies as a Diagnostic Marker for Cancer: A Meta-Analysis

Importance: The protein p53 is an unequivocal tumor suppressor that is altered in half of all cancers. The immune system produces systemic p53 autoantibodies (p53 Abs) in many cancer patients. Objective: This systemic review and meta-analysis focuses on the prognostic value of p53 Abs expressed in the serum of patients with solid tumors. Data Sources: All the clinical investigations were searched on PubMed from the first study dated 1993 until May 2021 (date of submission of the manuscript). Study Selection: Studies were included that met the following criteria: (1) participants with cancer; (2) outcome results expressed in relation to the presence of a p53 antibody; (3) a primary outcome (disease-free survival, overall survival or progression-free survival) expressed as hazard ratio (HR). The following exclusion criteria were used: (1) insufficient data available to evaluate outcomes; (2) animal studies; (3) studies with less than 10 participants. As a result, 12 studies were included in the analysis. Data Extraction and Synthesis: PRISMA guidelines were used for abstracting and assessing data quality and validity by three independent observers. The summary estimates were generated using a fixed-effect model (Mantel–Haenszel method) or a random-effect model (DerSimonian–Laird method), depending on the absence or presence of heterogeneity (I2). Main Outcome(s) and Measure(s): The primary study outcome was to determine the prognostic value of p53 Abs from a large population of patients with solid tumors, as determined before data collection. Results: In total, 12 clinical studies involving 2094 patients were included in the meta-analysis, and it was determined that p53 Abs expression in the serum significantly correlated with poorer survival outcomes of cancer patients (95% CI 1.48 [1.24, 1.77]; p < 0.00001). Conclusions and Relevance: This is the first meta-analysis proving the diagnostic utility of p53-Abs for cancer patients in predicting poorer outcomes. The serum-p53 value (s-p53-value) may be useful for future theranostics