Dental agenesis - a congenital lack of teeth - is one of the most frequently diagnosed developmental defects of dentition. Genetics is a crucial factor in the etiology of this disorder. Missing teeth can be caused by mutation in genes including MSX1, PAX9, AXIN2, and EDARADD. As is also true for ovarian cancer, over 20% of cases are associated with hereditary factors. Mutations in the BRCA1 and BRCA2 genes are said to be the most frequent of these. The aim of this study was to provide a systematic review of the literature on the coexistence of ovarian cancer and tooth agenesis.

CD28H and B7-H5 have been identified as receptor-ligand pairs in the B7/CD28 family, and have co-stimulatory activity in immune cells. Here, we have systematically reviewed the research reports concerning the CD28H/B7-H5 pathway. It was found that CD28H is mainly expressed in T cells and natural killer (NK) cells with naive and poorly differentiated properties, and repeated antigen stimulation leads to permanent loss of CD28H. In tumors, CD28H is mainly expressed in tissue-resident memory (TRM ) lymphocyte T cells, which is associated with improved tumor prognosis. B7-H5 is a ligand for CD28H and is widely expressed in tumor cells. B7-H5 expression is closely related to the prognosis of the tumor. Studies have shown that high expression of B7-H5 in tumor is related to a worse prognosis for lung cancer, osteosarcoma, oral squamous cell carcinoma (OSCC), breast carcinoma, human clear cell renal cell carcinoma (ccRCC), intrahepatic cholangiocarcinoma (ICC), bladder urothelial carcinoma (BUC) and colorectal cancer (CRC), but is associated with a better prognosis for pancreatic ductal adenocarcinoma (PDAC) and glioma. Controversial views exist in studies on gastric cancer prognosis.

To provide a comprehensive summary of risk factors, molecular machinery as well as potential therapeutic targets with a particular focus on literature published in the last 2 years on prognosis and treatment of penile cancer (PeCa).

Several meta-analyses have evaluated the value of biomarkers in diagnosing breast cancer, but which biomarker has the optimal diagnostic value remains unclear. This overview aimed to compare the accuracy of different biomarkers in diagnosing breast cancer. PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science were searched. The assessment of multiple systematic reviews-2 (AMSTAR-2) was used to assess the methodological quality and preferred reporting items for a systematic review and meta-analysis of diagnostic test accuracy (PRISMA-DTA) for reporting quality. Pairwise meta-analyses were performed to estimate the pooled results for each biomarker, and indirect comparisons were conducted to compare diagnostic accuracy between biomarkers. Eleven systematic reviews (SRs) involving 218 original studies were included. All SRs were of critically low methodological quality, 3 SRs had minimal reporting flaws and 8 SRs had minor flaws. The pooled sensitivity and specificity were 0.77 and 0.87 for miRNA, 0.70 and 0.87 for circulating cell-free DNA, 0.29 and 0.96 for APC gene promoter methylation, 0.69 and 0.99 for 14-3-3σ promoter methylation, 0.63 and 0.82 for CA153, 0.58 and 0.87 for CEA, and 0.73 and 0.56 for PSA. Compared with CA153 and PSA, miRNA had a higher sensitivity and specificity. The sensitivity of miRNA was higher than circulating cell-free DNA and CEA, although they had the same specificities. APC gene promoter methylation and 14-3-3σ promoter methylation were more specific than miRNA, but they had unacceptably low sensitivity. In conclusion, miRNA had better diagnostic accuracy than the other six biomarkers. But due to the low quality of included SRs, the results need to be interpreted with caution. Further study should investigate the diagnostic accuracy of different biomarkers in direct comparisons and focus on the value of combined biomarkers.

Previous studies investigated the prognostic role of programmed death-ligand 1 (PD-L1) expression in patients with biliary tract cancer (BTC); however, the results remained controversial. Therefore, we conducted the current meta-analysis with the aim of clarifying the association between PD-L1 expression and prognosis as well as with several important clinicopathological features of BTC. We searched PubMed, Embase, and Web of Science for relevant studies. Studies that detected PD-L1 expression in tumor cells by using immunohistochemistry (IHC) were selected. Pooled hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the correlations. In total, 15 independent studies with 1,776 patients were included in this meta-analysis. The pooled data demonstrated that high PD-L1 expression was associated with poor overall survival (n=15, HR=1.79, 95% CI=1.55-2.07, p<0.001). The correlation between PD-L1 expression and disease-free survival was not significant (n=6, HR=1.38, 95% CI=1.00-1.91, p=0.051). In addition, no significant correlation was observed between PD-L1 expression and clinical features in patients with BTC. Our study results showed that PD-L1 expression could play a pivotal role as an effective factor of poor prognosis in patients with BTC.

A meta-analysis was formulated to appraise the diagnostic accuracy of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC).

Molecular profiling of tumor derived cell free DNA (cfDNA) is gaining ground as a prognostic and predictive biomarker. However to what extent cfDNA reflects the full metastatic landscape as currently determined by tumor tissue analysis remains controversial. Though technically challenging, whole exome sequencing (WES) of cfDNA enables thorough evaluation of somatic alterations. Here, we review the feasibility of WES of cfDNA and determine the sensitivity of WES-detected single nucleotide variants (SNVs) in cfDNA on individual patient data level using paired tumor tissue as reference (sharedSNVsAlltissueSNVs×100%). The pooled sensitivity was 50% (95% credible interval (CI): 29-72%). The tissue mutant allele frequency (MAF) of variants exclusively identified in tissue was significantly lower (12.5%, range: 0.5-18%) than the tissue MAF of variants identified in both tissue and cfDNA (23.9%, range: 17-38%), p = 0.004. The overall agreement (sharedSNVsAllSNVs×100%)between SNVs in cfDNA and tumor tissue was 31% (95% CI: 15-49%). The number of detected SNVs was positively correlated with circulating tumor DNA (ctDNA) fraction (p = 0.016). A sub analysis of samples with ctDNA fractions ≥ 25% improved the sensitivity to 69% (95% CI: 46-89%) and agreement to 46% (95% CI: 36-59%), suggesting that WES is mainly feasible for patients with high ctDNA fractions. Pre- and post-analytical procedures were highly variable between studies rendering comparisons problematic. In conclusion, various aspects of WES of cfDNA are largely in its investigative phase, standardization of methodologies is highly needed to bring this promising technique to its clinical potential.

Microsatellite stable (MSS) BRAF p.V600E mutation colorectal cancer (BRAF-CRC) has a poor prognosis, whereas microsatellite instability (MSI) in BRAF-CRC is associated with a favorable prognosis. Although usually considered a single clinical entity, the MSI BRAF-CRC subtype shows some distinct characteristics in comparison with the MSS BRAF-CRC subtype.

Perivascular epithelioid cell tumor (PEComa) of the urinary bladder is a rare neoplasm showing distinct melanocytic and smooth muscle differentiation. We aimed to review the clinicopathologic features of bladder PEComa using all the available cases in the literature, along with 2 new cases from our database. The patients included 15 females and 15 males with a mean age of 39.2 ± 15.3 years. Painless hematuria was the most common clinical presentation. The tumors were usually well circumscribed with a mean tumor size of 4.4 ± 2.7 cm. Bladder PEComas demonstrated nests, trabeculae, or sheets of epithelioid cells with intermixed spindled cells and numerous thin-walled vessels. Immunohistochemical studies showed that the tumors were positive for HMB45 (27/27), cathepsin (4/4), SMA (20/22), and caldesmon (3/3) and were negative for pan cytokeratin (0/18) and EMA (0/4). Molecular studies revealed that PEComa was associated with the TFE3 (n = 3) and EWSR1 (n = 1) gene rearrangements. Treatment included partial cystectomy (n = 18), transurethral resection (n = 8), and radical cystectomy (n = 4). Twenty patients had no evidence of disease during a mean follow-up time of 19.4 ± 17.2 months. Two patients had recurrence, and 1 patient died of metastatic disease. In conclusion, bladder PEComas demonstrate distinct morphologic and immunohistochemical features. Although most tumors follow a benign course, a small subset may develop metastasis and cause death.

Studies have shown that the prevalence of RAS and BRAF mutations may differ by tumor sidedness among metastatic colorectal cancer (mCRC) patients. Both mutation status and tumor sidedness may impact survival and disease progression and RAS mutation status has been shown to predict response to anti-epidermal growth factor receptor (EGFR) therapy. A systematic literature review and meta-analysis were conducted to estimate the pooled prevalence of RAS and BRAF mutations by tumor sidedness in studies of mCRC patients. Forty-four studies comprising 15 981 mCRC patients tested for RAS and/or BRAF mutations were included in the meta-analyses. The prevalence of RAS mutations differed significantly by tumor side (32.4% among left-sided tumors, 41.3% among right-sided tumors; P = .017), as did the prevalence of KRAS mutations (35.8% among left-sided tumors, 46.3% among right-sided tumors; P < .0001) and BRAF mutations (4.3% among left-sided tumors, 16.3% among right-sided tumors; P < .0001). Among right-sided tumors, the prevalence of RAS and KRAS mutations varied significantly by study design, with higher prevalence among observational studies than clinical trials, and there was significant variation by study location for the prevalence of KRAS mutations in left-sided tumors and the prevalence of BRAF mutations in right-sided tumors. These results help to better characterize the mCRC population to better inform clinicians and researchers. Few of the included studies reported overall or progression-free survival (PFS) by both tumor sidedness and mutation status. As both of these factors may have prognostic impact, future studies should consider evaluating survival by these variables.

This study aims to assess the relationship between Rab1A expression and clinicopathological parameters and prognosis of patients with human solid cancer by summarizing the studies included.

Aim: A meta-analysis was conducted to assess the application of circulating cell-free DNA (cfDNA) in non-small-cell lung carcinoma (NSCLC) screening, EGFR and KRAS mutation detection. Materials & methods: A comprehensive literature search was conducted. The summary sensitivity and specificity for cfDNA in NSCLC diagnosis, EGFR and KRAS mutation detection were calculated. Results: The sensitivity and specificity for NSCLC diagnosis, EGFR and KRAS mutation detection were 0.80 (95% CI: 0.72-0.87) and 0.81 (95% CI: 0.68-0.91), 0.780 (95% CI: 0.711-0.853) and 0.962 (95% CI: 0.942-0.984), 0.628 (95% CI: 0.244-0.919) and 0.959 (95% CI: 0.932-0.998), respectively. Conclusion: cfDNA was a minimally invasive approach for NSCLC diagnosis, but its clinical utility warranted more future investigations because of the suboptimal sensitivity.

The impact of KRAS mutation status on outcomes of metastatic colorectal cancer (mCRC) treated with anti-angiogenic agents is controversial. A total of 4,066 mCRC patients from nine randomized controlled trials (RCTs) were included for analysis. The pooled results showed that the use of anti-angiogenic agents significantly improved progression-free survival (PFS) in mCRC patients with KRAS wide type (HR 0.63, 95%CI: 0.53-0.75, p<0.001) or mutated (HR 0.55, 95%CI: 0.38-0.79, p=0.001). In addition, the use of anti-angiogenic agents significantly improved overall survival (OS) in mCRC patients with KRAS wide type (HR 0.78, 95%CI: 0.70-0.86, p<0.001) or KRAS mutant status (HR 0.87, 95%CI: 0.77-0.98, p=0.018). No publication bias was detected for OS and PFS in mCRC patients. The findings of this study show that the use of anti-angiogenic agents significantly improved PFS and OS in mCRC independent of K-RAS gene status. KRAS gene status does not significantly influence the activity of antiangiogenic agents.

Despite remarkable improvements in survival of childhood acute lymphoblastic leukemia (ALL), nonresponding or relapsing patients still represent one of the most frequent causes of death by disease in children. Accurate patient risk stratification based on genetic markers could increases survival rates. miRNAs can represent novel candidates with diagnostic, predictive and prognostic potential; however, many groups investigated their involvement with contradictory results. Aim: To clarify the role of miRNAs as biomarkers through a systematic review. Results: From a revision of 45 manuscripts, we found that miR-128 and miR-181 overexpression could represent markers for ALL diagnosis and underexpression of miR-708 and miR-99a could be markers for bad prognosis. Conclusion: These signatures could refine classification and risk stratification of patients and improve ALL outcome.

Recently, extensive researches have explored the potential biomarker roles of microRNA-210 (miR-210) in non-small cell lung cancer (NSCLC). Inconsistent results, however, have prevented its widespread use in diagnosis. In the present study, we aimed to clarify the biomarker roles of miR-210 in NSCLC through a comprehensive meta-analysis and an integrative bioinformatics analysis.

This guideline provides recommendations for available tissue-based prostate cancer biomarkers geared toward patient selection for active surveillance, identification of clinically significant disease, choice of postprostatectomy adjuvant versus salvage radiotherapy, and to address emerging questions such as the relative value of tissue biomarkers compared with magnetic resonance imaging.

To provide an understanding of the role of common genetic variations in colorectal cancer (CRC) risk, we report an updated field synopsis and comprehensive assessment of evidence to catalogue all genetic markers for CRC (CRCgene2).

Deregulated miR-379/miR-656 cluster expression is considered as important for carcinogenesis and can be used as a potential prognostic marker. Hence, the meta-analysis was conducted to test the utility of miR-379/miR-656 cluster as a prognostic marker in various cancers. A literature search was performed using Web of Science, PubMed and Cochrane Library to obtain relevant studies and were subjected to various subgroup and bioinformatics analyses. Selected twenty-three studies contained 13 cancer types comprising of 3294 patients from 7 nations. Univariate and multivariate data showed an association of high expression of miRNAs with the poor prognosis of cancer patients (p < 0.001). The subgroup analysis showed that lung cancer, breast cancer and papillary renal cell carcinoma (p < 0.001) have a negative association with the survival of patients. Our study is the first meta-analysis showing the association of miR-379/miR-656 cluster expression and overall survival, suggesting its potential as a prognostic indicator in multiple cancers.

To analyze outcomes of non-small cell lung cancer (NSCLC) patients with brain metastases harboring EGFR or ALK mutations and examine for differences between tyrosine kinase inhibitors (TKIs) alone, radiotherapy (RT) alone (either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS)), or combined TKIs and RT.

In patients with thyroid fine-needle aspiration (FNA) report of suspicious for malignancy (SFM), both lobectomy and thyroidectomy might be considered. BRAF mutation analysis could guide towards accurate surgical therapy. The primary outcome was the reliability of BRAF (V600E) in detecting malignancy in nodules with FNA reading of SFM. The secondary outcome was to analyze its positive predictive value (PPV) and negative predictive value (NPV) considering the surgical histology as gold standard. A literature search of online databases was performed in June 2019. BRAF prevalence among thyroid nodules with FNA read as SFM according to the most popular classification systems (i.e., Bethesda V, Thy4, TIR4 category) was searched. The random-effects model was used. Three hundred sixty original articles were identified and 34 were finally included in the study. There were 1428 thyroid nodules with FNA read as SFM and 1287 (90.1%) lesions underwent surgery with a cancer rate 89.6%. The pooled prevalence of BRAF (V600E) mutation among all nodules with SFM cytology was 47% (95% CI = 40 to 54, I2 = 85.5%). Pooled PPV and NPV of BRAF testing were 99% (95% CI, 97-99) and 24% (95% CI, 16-32), respectively. BRAF (V600E) mutation was found in about one in two nodules with thyroid FNA read as SFM, its PPV to detect cancers was excellent, and its NPV was very poor. The routine BRAF testing in FNA read as SFM cannot be recommended. BRAF (V600E) test may be useful to extend surgical approach in selected cases with further suspicious clinical/ultrasound features.