The previous studies on angiotensin converting enzyme (ACE) insertion/deletion (I/D) genetic polymorphism and glioma risk were inconsistent. Therefore, we performed a meta-analysis to assess the association between ACE I/D polymorphisms and glioma risk.

Despite numerous reports in syndromic gliomas, the underlying genetic and molecular basis of familial, non-syndromic gliomas, in first degree relatives, remains unclear. This rare cohort of patients harboring invasive primary brain tumors with poor prognosis may provide a potential substrate of understanding the complex genetic cascade triggering tumorigenesis.

To compare the efficacy and safety of treatments based on the Stupp protocol for adult patients with newly diagnosed glioblastoma and to determine the optimal treatment option for patients with different O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation statuses. We estimated hazard ratios (HRs) for overall survival (OS) and odds ratios (ORs) for adverse events of grade 3 or higher (AEs ≥ 3). Twenty-one randomized controlled trials involving 6478 patients treated with 21 different treatment strategies were included. Results of the pooled HRs indicated tumor-treating fields (TTF) combined with the Stupp protocol resulted in the most favorable OS for patients with and without MGMT promoter methylation. Subgroup analyses by the two MGMT promoter statuses indicated that lomustine-temozolomide plus radiotherapy or TTF combination therapy was associated with the best OS for patients with methylated MGMT promoter (HR, 1.03; 95% credible interval [CI], 0.54-1.97), and standard cilengitide combination therapy or TTF combination treatment was associated with the best OS for patients with unmethylated MGMT promoter (HR, 1.05; 95% CI, 0.67-1.64). Regarding AEs ≥ 3, there were no significant differences in pooled ORs. However, Bayesian ranking profiles that demonstrated intensive cilengitide combination therapy and TTF combination therapy have a similar possibility to cause the least toxicity. These results indicated that TTF combination therapy was associated with increased survival, irrespective of the MGMT promoter methylation status, and a relatively tolerated safety profile compared with other combination treatments. The optimal treatment option for glioblastoma patients with different MGMT promoter methylation statuses was different.

Methylated cell-free DNA in liquid biopsies are promising non-invasive biomarkers for colorectal cancer (CRC). Optimal markers would have high sensitivity and specificity for early detection of CRC and could be detected in more than one type of material from the patient. We systematically reviewed the literature on DNA methylation markers of colorectal cancer, detected in more than one type of material, regarding their potential as contributors to a panel for screening and follow-up of CRC.

This objective of this systematic review was to estimate live birth rate and explore prognostic indicators in fetuses with 45,X karyotype and a posterior cystic hygroma (CH). Electronic databases were searched and studies reporting pregnancy outcomes (termination, spontaneous abortion, demise, or live birth) for fetuses with 45,X karyotype and a CH diagnosed on ultrasound were included. For cases of survival, CH characteristics, presence of hydrops fetalis, or concomitant anomalies, delivery details, and postnatal outcomes were summarized. A total of 95 studies, including 535 cases, met inclusion criteria: 285 (53.3%) pregnancies were terminated, 72 (13.5%) had spontaneous abortion or demise, 164 (30.7%) had unspecified pregnancy failure, and 14 (2.6%) were live births. Among live births with data available, all CH measured 2-7 cm, more than half were septate, and almost all regressed in size or eventually disappeared. Hydrops fetalis was noted in five cases. Of the eight live births with neonatal outcomes available, three neonates died shortly after birth and five survived past the neonatal period. This review suggests that diagnosis of CH in a 45,X fetus is associated with an estimated live birth rate of 2.6%, but only 1% survive to infancy. Prognosis appears to improve with CH regression.

The objective of this meta-analysis was to estimate the association of ACE I/D, -240 A > T and AT1R 1166 A > C polymorphisms with breast cancer (BC) risk. A comprehensive search on databases was conducted to identify all eligible case-control studies. Finally, 35 case-control studies, including 20 studies for ACE I/D, seven studies for ACE 240 A > T, and eight studies for AT1R 1166 A > C were included. The pooled analysis showed a significant association between ACE I/D polymorphism and BC risk under three genetic models, i.e., heterozygote (ID vs. DD: OR = 0.707, 95% CI 0.528-0.946, p = 0.020), homozygote (II vs. DD: OR = 0.662, 95% CI 0.462-0.947, p = 0.024), and dominant (II + ID vs. DD: OR = 0.691, 95% CI 0.507-0.941, p = 0.019). A significant association was also observed in ACE I/D polymorphism with BC risk among Asians and Caucasians. However, ACE -240 A > T and AT1R 1166 A > C polymorphisms were not associated with BC. Stratified analyses by ethnicity showed a significant association of ACE -240 A > T and AT1R 1166 A > C polymorphisms with BC risk in Latinos populations, but not in Asians. This meta-analysis inconsistence with all previous meta-analyses suggests that the ACE I/D might be associated with BC in overall and by ethnicity. However, the ACE -240 A > T and AT1R 1166 A > C were associated with BC risk only among Latinos populations.

The epidermal growth factor receptor (EGFR) mutation status related to the treatment approach for advanced non-small cell lung cancer (NSCLC) patients. This study aimed to evaluate the diagnostic accuracy of peripheral blood circulating tumor DNA (ctDNA) in EGFR mutated advanced NSCLC patients.

Non-coding RNA-activated by DNA damage (NORAD), a novel identified lncRNA, was found to be aberrantly expressed in various types of cancer. This meta-analysis was performed to evaluate the value of lncRNA NORAD as a prognostic biomarker in human cancers.

The aim of the present study was to systematically review the role of circulating miRNAs as potential prognostic biomarkers in head and neck cancer patients.

Hyperparathyroidism is an almost universal feature of multiple endocrine neoplasia type 1 syndrome. We present a systematic review and meta-analysis of the postoperative outcomes of patients undergoing initial operative treatment of primary hyperparathyroidism complicating multiple endocrine neoplasia 1.

Head and neck squamous cell carcinoma (HNSCC) is a group of tumours which exhibit low 5 year survival rates. Thus, there is an urgent need to identify biomarkers that may improve the clinical utility of patients with HNSCC. Emerging studies support a role of toll-like receptors (TLRs) in carcinogenesis. Therefore, this systematic review and meta-analysis was performed to assess the prognostic value of TLR immunoexpression in HNSCC patients. We compiled the results of thirteen studies comprising 1825 patients, of which six studies were deemed qualified for quantitative synthesis. The higher immunoexpression of TLR-1 to 5 and 9 was associated with a worsening of the clinical parameters of patients with HNSCC. Furthermore, induced levels of TLR-3, 4, 5, 7 and 9 were found to predict the patients' survival time. The meta-analysis revealed that TLR-7 overexpression is associated with a decreased mortality risk in HNSCC patients (HR 0.51; 95%CI 0.13-0.89; I2 34.6%), while a higher expression of TLR-5 predicted shorter, but non-significant, survival outcome. In conclusion, this review suggests that TLRs may represent some prognostic value for patients with HNSCC. However, due to small sample sizes and other inherent methodological limitations, more well designed studies across different populations are still needed before TLRs can be recommended as a reliable clinical risk-stratification tool.

Homologous recombination repair deficiency (HRD) is a frequent feature of high-grade serous ovarian, fallopian tube and peritoneal carcinoma (HGSC) and is associated with sensitivity to PARP inhibitor (PARPi) therapy. HRD testing provides an opportunity to optimise PARPi use in HGSC but methodologies are diverse and clinical application remains controversial.

The prognostic significance and optimal management of tetraploidy/near-tetraploidy acute myeloid leukemia (T/NT AML) remains unclear given its limited data. This is especially true after factoring in additional chromosomal alterations, which carry their own prognostic weight. Here, we analyze 128 cases of T/NT in AML from the literature along with two additional cases, which is the largest review of this subject to date. Based on our retrospective analysis, we found that regardless of the risk status attributed to cytogenetics, the prognosis of tetraploid or near-tetraploid AML is dismal and should be incorporated within the unfavorable risk group. Complete remission is paramount to survival in this population. Specific induction protocols for high-risk AML appear to have higher rates of complete remission in the T/NT AML population. Moreover, longer overall survival can be achieved with chemotherapy followed by allogeneic stem cell transplantation at first complete remission.

Background: Multiple studies have explored the prognostic role and clinical significance of the expression of the programmed cell death-1 (PD-1) gene in hepatocellular carcinoma (HCC). However, the results have been inconsistent. This study evaluated PD-1 expression and its clinical significance in patients with HCC, as well as the correlation between HCC pathological features and prognoses. Methods: All related research in PubMed, Embase, and Web of Science prior to October 31, 2019, was retrieved. The Newcastle-Ottawa Scale was used to evaluate the quality of the literature. Stata 14.0 statistical software was used to analyze the data, and the correlations between PD-1 expression and the clinicopathological characteristics of patients were analyzed using the odds ratio (OR) and its 95% confidence interval (CI). The hazard ratio (HR) and its 95% CI were used to analyze the correlation between PD-1 high expression and patient prognosis. Begg's test was used to evaluate publication bias. Results: A total of 581 patients were analyzed in the six studies included in the meta-analysis. Pooled analysis revealed that high levels of PD-1 expression did not correlate with overall survival (HR = 0.79; 95% CI: [0.41-1.54]; p = 0.493). PD-1 positivity was associated with better disease-free survival (HR = 0.52; 95% CI: [0.38-0.72]; p < 0.0001). Furthermore, elevated PD-1 expression corrected for age (OR = 0.62, 95% CI: [0.41-0.96]; p = 0.030) and alpha-fetoprotein levels (OR = 2.27, 95% CI: [1.46-3.55]; p < 0.0001), were not correlated with patient sex, tumor size, tumor multiplicity, hepatitis B virus history, tumor node metastasis stage or Barcelona Clinic Liver Cancer stage. Conclusions: This meta-analysis revealed that PD-1 expression may be a useful prognostic marker in HCC patients. Prospective clinical studies are needed to support these findings.

The prognostic and clinicopathological significance of POU Class 5 Homeobox 1 (POU5F1) among various cancers are disputable heretofore. The diagnostic value and functional mechanism of POU5F1 in liver hepatocellular carcinoma (LIHC) have not been studied thoroughly.

The addition of daratumumab to backbone multiple myeloma (MM) regimens is associated with improved response rates and progression-free survival (PFS). Whether improved outcomes are also associated with this regimen among patients with cytogenetically defined high-risk MM (HRMM) remains unclear.

Several biomarkers such as tumor mutation burden (TMB), neoantigen load (NAL), programmed cell-death receptor 1 ligand (PD-L1) expression, and lactate dehydrogenase (LDH) have been developed for predicting response to immune checkpoint inhibitors (ICIs) in melanoma. However, some limitations including the undefined cut-off value, poor uniformity of test platform, and weak reliability of prediction have restricted the broad application in clinical practice. In order to identify a clinically actionable biomarker and explore an effective strategy for prediction, we developed a genetic mutation model named as immunotherapy score (ITS) for predicting response to ICIs therapy in melanoma, based on whole-exome sequencing data from previous studies. We observed that patients with high ITS had better durable clinical benefit and survival outcomes than patients with low ITS in three independent cohorts, as well as in the meta-cohort. Notably, the prediction capability of ITS was more robust than that of TMB. Remarkably, ITS was not only an independent predictor of ICIs therapy, but also combined with TMB or LDH to better predict response to ICIs than any single biomarker. Moreover, patients with high ITS harbored the immunotherapy-sensitive characteristics including high TMB and NAL, ultraviolet light damage, impaired DNA damage repair pathway, arrested cell cycle signaling, and frequent mutations in NF1 and SERPINB3/4. Overall, these findings deserve prospective investigation in the future and may help guide clinical decisions on ICIs therapy for patients with melanoma.

Isocitrate dehydrogenase (IDH) mutation status has important prognostic implications in glioma patients, with IDH wild-type (IDH-WT) gliomas being associated with worse prognosis and shorter survival when compared with IDH mutant (IDH-mut) gliomas. Optimization of quality of life is a priority in the management of glioma patients. The goal of this systematic review was to identify studies that explored the association of IDH mutation status with patient-reported outcomes (PROs) and cognitive functioning of glioma patients.

To assess the expression and clinical value of miR-19 in gastrointestinal malignancy. Setting. Embase, Web of Science, PubMed, and other databases were retrieved to screen out relevant studies until December 31, 2019. Participants. Gastrointestinal cancer patients with the description of miR-19 expression, as well as the correlation between miR-19 and clinicopathological characteristics or prognosis. Main Outcome Measures. Pooled odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI) was obtained to determine miR-19 expression in gastrointestinal malignancy and the association between miR-19 and patients' clinical characteristics and survival.

Background: Five EGFR-tyrosine kinase inhibitors (EGFR TKIs) are currently available in the first-line setting for non-small-cell lung cancer (NSCLC) in Japan. The aim here was to compare the relative efficacy of EGFR TKIs in the Japanese population. Materials & methods: A systematic review identified randomized controlled trials examining the efficacy of first-line EGFR TKIs. A Bayesian network meta-analysis was used to assess these EGFR TKI comparisons for progression-free survival (PFS). Results: A total of seven randomized controlled trials were identified and considered for network meta-analysis. Dacomitinib showed a trend toward improved PFS versus all comparators. Conclusion: Dacomitinib demonstrated a trend toward improved PFS and therefore, should be considered one of the standard first-line therapies for Japanese patients diagnosed with EGFR+ non-small-cell lung cancer.