Immune checkpoint inhibitors (ICIs) have changed the treatment pattern of advanced and metastatic NSCLC. A series of ICI based therapies have emerged in the first-line treatment field, but the comparative efficacy was unclear.

The rate of pathological complete response (pCR) with both chemotherapy alone (CT) and endocrine therapy (ET) in the neoadjuvant (Na) treatment of hormone receptor (HR)-positive/HER2-negative breast cancer (BC) is unsatisfactory. Limited data on neoadjuvant concomitant chemotherapy and endocrine therapy (NaCET) are available.

Adult gliomas are divided into isocitrate dehydrogenase (IDH) wild-type and IDH mutant subtypes according to the new 2021 World Health Organization classification system. However, the local and systemic effects of IDH mutations on primary glioma patients are not well illustrated. Retrospective analysis, immune-cell infiltration analysis, meta-analysis, and immunohistochemistry assay were applied in the present study. The results from our cohort showed that IDH mutant gliomas own a lower proliferating rate compared to that in wild-type gliomas. Patients with mutant IDH exhibited a higher frequency of seizures in both our cohort and the cohort from the meta-analysis. Mutations in IDH result in lower levels of intra-tumour but higher levels of circulating CD4+ and CD8+ T lymphocytes. Levels of neutrophils in both intra-tumour and circulating blood were lower in IDH mutant gliomas. Moreover, IDH mutant glioma patients receiving radiotherapy in combination with chemotherapy exhibited better overall survival with respect to radiotherapy alone. Mutations in IDH alters the local and circulating immune microenvironment, and increases the sensitivity of tumour cell to chemotherapy.

Using meta-analyses, we introduce a unicellular attractor (UCA) model integrating essential features of the 'atavistic reversal', 'cancer attractor', 'somatic mutation', 'genome chaos', and 'tissue organization field' theories. The 'atavistic reversal' theory is taken as a keystone. We propose a possible mechanism of this reversal, its refinement called 'gradual atavism', and evidence for the 'serial atavism' model. We showed the gradual core-to-periphery evolutionary growth of the human interactome resulting in the higher protein interaction density and global interactome centrality in the UC center. In addition, we revealed that UC genes are more actively expressed even in normal cells. The modeling of random walk along protein interaction trajectories demonstrated that random alterations in cellular networks, caused by genetic and epigenetic changes, can result in a further gradual activation of the UC center. These changes can be induced and accelerated by cellular stress that additionally activates UC genes (especially during cell proliferation), because the genes involved in cellular stress response and cell cycle are mostly of UC origin. The functional enrichment analysis showed that cancer cells demonstrate the hyperactivation of energetics and the suppression of multicellular genes involved in communication with the extracellular environment (especially immune surveillance). Collectively, these events can unleash selfish cell behavior aimed at survival at all means. All these changes are boosted by polyploidization. The UCA model may facilitate an understanding of oncogenesis and promote the development of therapeutic strategies.

Multiple myeloma (MM) is an incurable disease characterized by the presence of malignant plasma cells in the bone marrow that secrete specific monoclonal immunoglobulins into the blood. Obesity has been associated with the risk of developing solid and hematological cancers, but its role as a risk factor for MM needs to be further explored. Here, we evaluated whether 32 genome-wide association study (GWAS)-identified variants for obesity were associated with the risk of MM in 4189 German subjects from the German Multiple Myeloma Group (GMMG) cohort (2121 MM cases and 2068 controls) and 1293 Spanish subjects (206 MM cases and 1087 controls). Results were then validated through meta-analysis with data from the UKBiobank (554 MM cases and 402,714 controls) and FinnGen cohorts (914 MM cases and 248,695 controls). Finally, we evaluated the correlation of these single nucleotide polymorphisms (SNPs) with cQTL data, serum inflammatory proteins, steroid hormones, and absolute numbers of blood-derived cell populations (n = 520). The meta-analysis of the four European cohorts showed no effect of obesity-related variants on the risk of developing MM. We only found a very modest association of the POC5rs2112347G and ADCY3rs11676272G alleles with MM risk that did not remain significant after correction for multiple testing (per-allele OR = 1.08, p = 0.0083 and per-allele OR = 1.06, p = 0.046). No correlation between these SNPs and functional data was found, which confirms that obesity-related variants do not influence MM risk.

Survivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI.

Previous studies found that the circadian clock gene participated in the genesis and development of breast cancer. However, research findings on the relationship between polymorphisms in the CLOCK gene and breast cancer risk were inconsistent. This study performed a meta-analysis of the association between CLOCK gene polymorphisms and breast cancer risk. PubMed, Cochrane Library, and Embase databases were electronically searched to collect studies on the association between CLOCK gene polymorphisms and breast cancer risk from inception to February 14, 2022. The quality of the included literature was assessed using the Newcastle-Ottawa Scale. For statistical analysis, odds ratio (OR) and 95% confidence intervals (CIs) were calculated using STATA 14.0. In addition, publication bias was performed by the funnel diagram and the Harbord's regression test. And sensitivity analysis was assessed by the trim and fill method. A total of 6 eligible studies, including 10,164 subjects (5488 breast cancer cases and 4676 controls), were screened in this meta-analysis. Though we did not find a significant association between the polymorphisms in the overall CLOCK gene with breast cancer risk [OR (95%CI) = 0.98 (0.96, 1.01), P = 0.148], we found that compared with T/T types of rs3749474 in CLOCK, T/C and C/C types of rs3749474 were associated with lower risk of breast cancer [OR (95%CI) = 0.93 (0.88, 0.98), P = 0.003]. The sensitivity analysis confirmed the robustness of the results. The funnel plot showed no significant publication bias. Polymorphisms in the CLOCK gene might be associated with breast cancer risk. More studies are needed to confirm the conclusion.

Background: Circulating tumour DNA (ctDNA) has demonstrated robust diagnostic accuracy in several digestive cancers. However, the prognostic role of ctCDNA in gastric cancer (GC) is still controversial. This systematic review and meta-analysis aimed to evaluate the prognostic value of ctDNA in GC.Methods: PubMed, Web of Science and Cochrane databases were searched to identify studies reporting the use of ctDNA to predict GC outcome and all relevant studies published until November 2022 were enrolled for our analysis. Data were extracted by two authors independently and statistic analysis was conducted by R program with 'meta' and 'metafor' packages.Results: A total of 34 qualified articles with 5091 subjects were incorporated into our meta-analysis. The corresponding Hazard ratio (HR) of overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS) were 2.74 (95% CI:2.24-3.35), 3.13 (95% CI:2.08-4.72) and 3.04 (95% CI:2.46-3.76), respectively, in GC patients.Conclusion: Blood-based ctDNA assay would be a potential novel biomarker for GC evaluation and prediction.Simple Summary: This is the integrated meta-analysis on the association of circulating tumour DNA (ctDNA) and prognosis of gastric cancer (GC) with an increasing number of studies exploring the prognostic value of GC in the last few years, which depicted that the detection of ctDNA could be a promising predictor in GC patients.

A high level of circulating tumor DNA (ctDNA) has been linked to poor survival in patients with certain solid tumors. In spite of this, it is still unclear whether ctDNA is associated with poor survival in small cell lung cancer (SCLC). To investigate the above association, we conducted a systematic review and meta-analysis. PubMed, Web of Science, Cochrane's Library, and Embase were searched for relevant cohort studies from the inception of the databases to November 28, 2022. Data collection, literature search, and statistical analysis were carried out independently by two authors. To account for heterogeneity, we used a random-effects model. In this meta-analysis, 391 patients with SCLC were identified, and the data were pooled from nine observational studies and followed for 11.4 to 25.0 months. A high ctDNA was associated with worse overall survival (OS, risk ratio [RR] 2.50, 95% confidence interval [CI]1.85 to 3.38, p < 0.001; I2 = 25%) and progression-free survival (PFS, RR 2.33, 95% CI 1.48 to 3.64, p < 0.001, I2 = 42%). Subgroup analyses retrieved consistent results in prospective and retrospective studies, in studies with ctDNA measured with polymerase chain reaction or next-generation sequencing, and in studies analyzed with univariate or multivariate regression models. Studies suggest that ctDNA may be an important factor in predicting poor OS and PFS in SCLC patients.

O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that maintains the stability of genetic information. MGMT is a strong prognostic biomarker in patients with glioblastoma. However, the effect of its gene hypermethylation and expression on the survival rate of head and neck cancer (HNC) patients is still disputed. Therefore, we conducted a meta-analysis to evaluate the prognostic value of MGMT hypermethylation and expression in HNC patients.

The PARP inhibitors (PARPis) olaparib and talazoparib are currently approved for the treatment of deleterious germline BRCA1/2-mutated (gBRCA+) metastatic breast cancer (MBC). These approvals were based on improvements in progression-free survival (PFS) observed in two randomized controlled trials (RCTs). Other PARPis, such as veliparib and niraparib, have also been studied. We conducted this meta-analysis of RCTs to assess the PFS and overall survival (OS) benefits of PARPis in gBRCA + MBC.

What is the influence of body composition during childhood, adolescence, and adulthood, as well as metabolic parameters, on incident polycystic ovary syndrome (PCOS)?

Human gut microbiome has complex relationships with the host, contributing to metabolism, immunity, and carcinogenesis.

Aberrant expression of lncRNAs in cancer cells can impact their key phenotypes. We aimed to summarize available evidence on clinicopathological and prognostic value of lncRNA TPT1-AS1 in cancer.

A new era of next-generation sequencing has changed our perception of the oral microbiome in health and disease, and with this there is a growing understanding that the oral microbiome is a contributing factor to oral squamous cell carcinoma (OSCC), a malignancy of the oral cavity. This study aimed to analyse the trends and relevant literature based on the 16S rRNA oral microbiome in head and neck cancer using next-generation sequencing technologies, and to conduct a meta-analysis of the studies with OSCC cases and healthy controls. A literature search using the databases Web of Science and PubMed was conducted in a scoping-like review to collect information based on the study design, and plots were generated using RStudio. We selected case-control studies using 16S rRNA oral microbiome sequencing analysis in OSCC cases versus healthy controls for re-analysis. Statistical analyses were conducted using R. Out of 916 original articles, we filtered and selected 58 studies for review, and 11 studies for meta-analysis. Differences between sampling type, DNA extraction methods, next-generation sequencing technology and region of the 16S rRNA were identified. No significant differences in the α- and β-diversity between health and oral squamous cell carcinoma were observed (p < 0.05). Random Forest classification marginally improved predictability of four studies (training set) when split 80/20. We found an increase in Selenomonas, Leptotrichia and Prevotella species to be indicative of disease. A number of technological advances have been accomplished to study oral microbial dysbiosis in oral squamous cell carcinoma. There is a clear need for standardization of study design and methodology to ensure 16S rRNA outputs are comparable across the discipline in the hope of identifying 'biomarker' organisms for designing screening or diagnostic tools.

JC Polyomavirus (JCV) is a human polyomavirus encoding T-antigen protein, which is implicated in carcinogenesis. JCV is prevalent in the upper and lower gastrointestinal track. Several studies have reported JCV associations with the risk of developing colorectal cancer (CRC), however, these findings remain controversial. Since JCV DNA may be present in healthy tissues as well as transformed tissues, JCV T-antigen expression could be a more useful measure of JCV's association with cancer development. The aim of this study is to conduct a meta-analysis of case-control studies to investigate if there is a significant association between JCV T-antigen protein expression and risk of CRC. A systematic review was performed to identify studies reporting JCV DNA prevalence in CRC and JCV T-antigen expression. The strength of the association was estimated by odds ratios (ORs). Five (of 66) studies satisfied analysis inclusion criteria, and spanned years 1999 to 2022. Random effects meta-analysis of CRC cases versus controls showed an 11-fold increased risk of CRC development in JCV DNA positive samples with JCV T-antigen expression versus normal tissues (OR 10.95; 95% CI: 2.48-48.24; P = 0.0016). The results of this meta-analysis of JCV infection followed by JCV T-antigen protein expression for the risk of CRC support the argument that JCV infection significantly increases the risk of colorectal cancer in tissues where the JCV T-antigen protein is expressed. Further research with JCV T-antigen expression in relation to CRC development is needed.

Several studies have revealed the relationships between telomere length and the risk and mortality of numerous cancers. This meta-analysis aims to insightfully clarify the potential relationship between telomere length and the recurrence of multiple cancers.

Extracellular matrix protein 2 (ECM2), which regulates cell proliferation and differentiation, has recently been reported as a prognostic indicator for multiple cancers, but its value in lower grade glioma (LGG) remains unknown. In this study, LGG transcriptomic data of 503 cases in The Cancer Genome Atlas (TCGA) database and 403 cases in The Chinese Glioma Genome Atlas (CGGA) database were collected to analyze ECM2 expression patterns and the relationship with clinical characteristics, prognosis, enriched signaling pathways, and immune-related markers. In addition, a total of 12 laboratory samples were used for experimental validation. Wilcoxon or Kruskal-Wallis tests demonstrated highly expressed ECM2 in LGG was positively associated with malignant histological features and molecular features such as recurrent LGG and isocitrate dehydrogenase (IDH) wild-type. Also, Kaplan-Meier (KM) curves proved high ECM2 expression could predict shorter overall survival in LGG patients, as multivariate analysis and meta-analysis claimed ECM2 was a deleterious factor for LGG prognosis. In addition, the enrichment of immune-related pathways for ECM2, for instance JAK-STAT pathway, was obtained by Gene Set Enrichment Analysis (GSEA) analysis. Furthermore, positive relationships between ECM2 expression with immune cells infiltration and cancer-associated fibroblasts (CAFs), iconic markers (CD163), and immune checkpoints (CD274, encoding PD-L1) were proved by Pearson correlation analysis. Finally, laboratory experiments of RT-qPCR and immunohistochemistry showed high expression of ECM2, as well as CD163 and PD-L1 in LGG samples. This study identifies ECM2, for the first time, as a subtype marker and prognostic indicator for LGG. ECM2 could also provide a reliable guarantee for further personalized therapy, synergizing with tumor immunity, to break through the current limitations and thus reinvigorating immunotherapy for LGG. AVAILABILITY OF DATA AND MATERIALS: Raw data from all public databases involved in this study are stored in the online repository (chengMD2022/ECM2 (github.com)).

A gene or variant has pleiotropic effects, and genetic variant identification across multiple phenotypes can provide a comprehensive understanding of biological pathways shared among different diseases or phenotypes. Discovery of genetic loci associated with multiple diseases can simultaneously support general interventions. Several meta-analyses have shown genetic associations with gastric cancer (GC); however, no study has identified associations with other phenotypes using this approach.

Studies have revealed that miR-21 is abnormally expressed in breast cancer patients, suggesting that miR-21 could be exploited as a possible diagnostic biomarker for clinical applications. In order to provide clinical evidence that is supported by research, we investigate the diagnostic utility of miR-21 in breast cancer in this study.