To evaluate the impact of PIK3CA mutation status on clinical outcomes of HR+ breast cancer treated with PI3K inhibitors.

According to previous studies, linc-UBC1 is abnormally expressed in various human tumours. Nonetheless, the clinical significance and mechanism of linc-UBC1 in cancer remains unclear. In our present analysis, we wanted to explore the specific role of linc-UBC1 in malignant tumours by integrating all of the relevant literature and subsequently elucidating the relationship between linc-UBC1 expression level and clinical characteristics of cancers. An elaborate database search of PubMed, Embase, Wanfang Data, Web of Science, Ovid, Medline, Cochrane Library and PMC was carried out up to 8 August 2019. We further applied the pooled odds ratio (OR) and hazard ratio (HR) to evaluate OS. After filtering by strict criteria, 11 studies containing 1017 cases were included in this analysis. Our results implied that high expression of linc-UBC1 was obviously related to poor OS in cancer (HR =1.735, 95% 1.348-2.235, p < .001 random effects model). Analogously, the data revealed that high expression of linc-UBC1 was highly correlated with lymph node metastasis (OR = 2.912, 95% CI: 2.056-4.125, p < .001 fix effects model) and high tumour stage (OR = 2.678, 95% CI: 1.859-3.857, p < .001 fix effects model). In summary, linc-UBC1 overexpression is associated with poor OS and advanced tumour stage and could be used as a novel prognostic biomarker in various cancers.

Genome-wide approaches applied for the identification of new hereditary colorectal cancer (CRC) genes, identified several potential causal genes, including RPS20, IL12RB1, LIMK2, POLE2, MRE11, POT1, FAN1, WIF1, HNRNPA0, SEMA4A, FOCAD, PTPN12, LRP6, POLQ, BLM, MCM9, and the epigenetic inactivation of PTPRJ. Here we attempted to validate the association between variants in these genes and nonpolyposis CRC by performing a mutational screening of the genes and PTPRJ promoter methylation analysis in 473 familial/early-onset CRC cases, a systematic review of the published cases, and assessment of allele frequencies in control population. In the studied cohort, 24 (5%) carriers of (predicted) deleterious variants in the studied genes and no constitutional PTPRJ epimutations were identified. Assessment of allele frequencies in controls compared with familial/early-onset patients with CRC showed association with increased nonpolyposis CRC risk of disruptive variants in RPS20, IL12RB1, POLE2, MRE11 and POT1, and of FAN1 c.149T>G (p.Met50Arg). Lack of association was demonstrated for LIMK2, PTPN12, LRP6, PTPRJ, POLQ, BLM, MCM9 and FOCAD variants. Additional studies are required to provide conclusive evidence for SEMA4A, WIF1, HNRNPA0 c.-110G>C, and FOCAD large deletions.

Epidermal growth factor receptor (EGFR) mutation testing is recommended for selecting patients with non-squamous non-small cell lung cancer (NSCLC) for EGFR tyrosine kinase inhibitor drug treatment.

Ovarian cancer is the deadliest of gynecologic malignancies with the 5-year overall survival rate remaining at approximately 30%, a rate that has not improved over the last three decades. Standard of care for epithelial ovarian cancer patients consists of a platinum compound with a taxane given intravenously following debulking surgery; however, 80% of cases relapse within 2 years of diagnosis. This review sought to identify key underlying biomarkers related to platinum resistance in ovarian cancer to establish possible prognostic biomarkers of chemoresponse.

While genomics provides new clinical opportunities, its complexity generates uncertainties. This systematic review aimed to summarize what is currently known about the experience of uncertainty for adult patients undergoing cancer genomic testing. A search of five databases (2001 to 2018) yielded 6508 records. After removing duplicates, abstract/title screening, and assessment of full articles, ten studies were included for quality appraisal and data extraction. Qualitative studies were subjected to thematic analysis, and quantitative data were summarized using descriptive statistics. Cancer genomic results reduced uncertainty for patients regarding treatment decisions but did not reduce uncertainty in the risk context. Qualitative and quantitative data synthesis revealed four themes: (1) coexisting uncertainties, (2) factors influencing uncertainty, (3) outcomes of uncertainty, and (4) coping with uncertainty. Uncertainty can motivate, or be a barrier to, pursuing cancer genomic testing. Appraisal of uncertainty influences the patient experience of uncertainty, the outcome of uncertainty for patients, as well as the coping strategies utilized. While this systematic review found that appraisal of uncertainty is important to the patients' experience of uncertainty in the cancer genomic context, more mixed methods longitudinal research is needed to address the complexities that contribute to patient uncertainty across the process.

Various pathologies and lifestyle factors, such as nutritional factors and physical exercises, can alter the gene expression of proteins related to synthesis and degradation.

Folate receptor alpha (FOLR1), a glycosylphosphatidylinositol-linked protein, is a well characterized folate transporter. However, the prognostic power of FOLR1 in cancer remains controversial. We conducted a meta-analysis to assess the prognostic roles of FOLR1 on different cancers. Twelve studies involving 4471 patients were included in this meta-analysis. The pooled analysis indicated that high FOLR1 significantly predicted poor overall survival (OS) (pooled hazard ratio (HR) = 0.78, 95% confidence interval (CI) = 0.64-0.94, p = 0.009) and the disease-free survival (DFS) (HR = 1.25, 95% CI = 1.07-1.47, p = 0.005). Subgroup analyses based on tumour type found that high FOLR1 level was associated with poor OS in breast cancer (HR = 2.66, 95% CI = 1.54-4.59, p = 0.0005) and endometrial carcinoma (HR = 1.30, 95% CI = 1.05-1.61, p = 0.02). However, FOLR1 has relatively weakly correlation with gender, tumour size and chemotherapy. Additionally, overexpression of FOLR1 was correlated with grade, FIGO stage, vital status and nodule status. The present meta-analysis indicated that the high expression of FOLR1 is associated with the poor survival of cancer patients, which is helpful for the clinical decision-making process.

To provide a comprehensive account of the association of five Lymphotoxin-α (LTA) gene polymorphisms (rs1041981, rs2229094, rs2239704, rs746868, rs909253) with susceptibility to cancer.

The risk of cardiovascular adverse events from rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is not fully characterized.

The mismatch repair (MMR) pathway plays a crucial role in repairing DNA replication errors in normal and cancer cells. Defects in DNA MMR proteins that determine the microsatellite instability-high (MSI-H) condition lead to the accumulation of mutations and the generation of neoantigens, which may stimulate the antitumor immune response. Clinical trials have demonstrated that MSI-H status is associated with long-term benefit in patients treated with immune checkpoint inhibitors (ICIs).

A variety of studies have evaluated the association of polymorphisms at endothelial nitric oxide synthase (eNOS) gene with risk of prostate cancer. However, the results remain inconclusive. This meta-analysis was performed to derive a more precise estimation between eNOS polymorphisms and prostate cancer risk.

Recent studies have found that metastatic castrated-resistant prostate cancer (mCRPC) with positive androgen receptor splice variant 7 (AR-V7) may have poor prognosis during endocrine or chemotherapy treatment, but the specific mechanism was still unclear. We had finished literature search in March 2019 from PubMed, Web of Science database, and Embase. The final results were presented in this research. The pooled results showed that AR-V7 status predicted pooled PSA-PFS (HR = 4.31, 95% CI: 2.57-7.24, p < .001), rPFS (HR = 2.39, 95% CI: 1.28-4.48, p = .006) and OS (HR = 4.27, 95% CI: 3.22-5.66, p < .001) in mCRPC patients after endocrine or chemotherapy treatment. Subgroup analysis of different treatments revealed that mCRPC patients treated with chemotherapy had significant association between positive AR-V7 and OS (HR = 2.82, 95% CI: 1.72-4.62, p < .001), and also during endocrine therapy (HR = 4.78, 95% CI: 3.33-6.86, p < .001). Our study demonstrated that AR-V7-positive mCRPC patients may have worse prognosis. AR-V7 may be an independent prognostic factor for endocrine therapy or chemotherapy in patients with mCRPC.

Human epidermal growth factor (HER2) is an oncogene that codes for HER2 protein. The gene is amplified, and protein is overexpressed in 20% of patients and carries a poor prognosis. HER2-positive tumors tend to be more aggressive and highly proliferative. In 2006, trastuzumab, a monoclonal antibody targeting HER2, was approved for use with chemotherapy as an adjuvant treatment for women with HER2-positive breast cancer. The drug has shown improved survival rates for women with HER2-positive breast cancer. As promised for survival in HER2-positive patients continues with new research, and as novel drug approvals emerge, HER2 assessment plays a significant role in adjuvant and in metastatic setting. HER2 assays approved by the US Food and Drug administration include immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and bright field dual in situ hybridization (DISH). Accuracy of HER2 testing across laboratories has an impact on treatment as false-negative testing can deprive the patients of trastuzumab therapy. The current review will focus on the variability of HER2 testing across laboratories and the potential impact on treatment.

Accumulating studies have confirmed that mammary serine protease inhibitor (MASPIN) plays an essential role in non-small cell lung cancer (NSCLC). However, results are still controversial or inconsistent. In the present study, we attempted to identify the clinical significance of MASPIN and its potential molecular roles in NSCLC. The correlation of MASPIN with prognosis and clinicopathological characteristics was assessed by meta-analysis. Additionally, the potential molecular mechanisms of MASPIN in NSCLC was also investigated through several online databases. A total of 2220 NSCLC patients from 12 high quality studies were included and the results indicated that up-regulated MASPIN nucleus and cytoplasm expression was associated with poor overall survival (OS) (hazard ratio (HR) = 1.43, 95% confidence interval (CI) = 1.01-2.04, P<0.05), elevated MASPIN cytoplasm expression was associated with poor OS (HR = 1.45, 95% CI = 1.01-2.07, P<0.05), disease-free survival (DFS) (HR = 1.95, 95% CI = 1.31-2.88, P=0.001), and disease-specific survival (DSS) (HR = 2.17, 95% CI = 1.18-3.99, P=0.013). MASPIN both nucleus and cytoplasm location were associated with clinicopathological characteristics. Bioinformatics analysis validated the above results and suggested that human serpin family B member 5 (SERPINB5) hypomethylated levels were negatively correlated with its mRNA expression. Bioinformatics analysis also revealed the 85 most frequently altered neighboring genes of SERPINB5, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed 20 GO terms and 3 KEGG pathways with statistical significance. MASPIN had a statistically negative correlation with NSCLC prognosis, functioning as an oncoprotein by hypomethylation and influencing specific pathways involving the 85 genes identified herein. MASPIN might be a promising prognostic signature in NSCLC.

The most recent cIMPACT-NOW update highlighted the homozygous deletion of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene as a clinically important molecular alteration in IDH-mutant glioma. Correspondingly, we systematically reviewed the contemporary literature to affirm the contemporary stance of the literature on the prognostic significance of this alteration in this setting based on the current World Health Organization (WHO) Grade classification.

Microsatellite instability (MSI) defines one of the four molecular groups of endometrial carcinoma identified by The Cancer Genome Atlas (TCGA). Immunohistochemistry for mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, PMS2) has been proposed as a widely applicable technique to identify this group in the common practice. However, the diagnostic accuracy of such approach has never been calculated. We aimed to assess: 1) the diagnostic accuracy of MMR proteins immunohistochemistry as surrogate of MSI molecular testing in endometrial carcinoma; 2) whether a combination of only two MMR proteins may be used as a still cheaper test. A systematic review and meta-analysis of was performed by searching electronic databases from their inception to September 2019. All studies assessing endometrial carcinoma with both MMR proteins immunohistochemistry and MSI molecular testing were included. Diagnostic accuracy was assessed as sensitivity, specificity, positive and negative likelihood ratios (LR+, LR-), diagnostic odds ratio (DOR) and area under the curve (AUC) on SROC curves. A subgroup analysis was performed for a combination of only two MMR proteins (MLH1-MSH2 vs MSH6-PMS2). Ten studies with 3097 patients were included. Out of these, 1110 were suitable for the meta-analysis. Immunohistochemistry for all the four MMR proteins showed sensitivity = 0.96, specificity = 0.95, LR + =17.7, LR- = 0.05, DOR = 429.77, and high diagnostic accuracy (AUC = 0.988). The combination of MLH1 and MSH2 showed sensitivity = 0.88, specificity = 0.96, LR + =22.36, LR- = 0.15, DOR = 200.69, and high diagnostic accuracy (AUC = 0.9838). The combination of MSH6 and PMS2 showed the same results as the complete panel of four MMR proteins. In conclusion, MMR proteins immunohistochemistry is a highly accurate surrogate of MSI molecular testing in endometrial carcinoma. A combination of MSH6 and PMS2 may allow reducing the cost without decrease in the diagnostic accuracy.

No overall survival (OS) benefit has been reported from a mature randomized trial with the use of ALK inhibitors. We conducted a systematic review and meta-analysis to assess the efficacy of ALK inhibitors compared to chemotherapy (ALK vs. chemo) and 2nd generation ALK inhibitors compared to 1 st generation ALK inhibitors (ALK-2 G vs. ALK-1 G).

A great number of DNA-damage repair (DDR) pathways have been recognized to be frequently dysregulated in advanced stages of prostate cancer. DNA-repair defects in prostate cancer represents a clinically relevant disease subset. Tumors whose ability to repair double-strand DNA breaks by homologous recombination is compromised, are highly sensitive to blockade of the repair of DNA single-strand breaks via the inhibition of the enzyme poly(ADP) ribose polymerase (PARP).

The evaluation of surgically resected papillary thyroid carcinomas (PTC) by immunohistochemistry (IHC) for BRAF mutation has diagnostic, prognostic and therapeutic implications. The goal of this meta-analysis was to perform a systematic review of studies using the VE1 clone (specific for detection of the BRAF V600E mutation) on formalin-fixed paraffin embedded (FFPE) thyroid surgical resection specimens for primary papillary thyroid carcinoma. The authors' molecular techniques, immunohistochemistry protocols, and scoring methods for VE1 immunostaining were also evaluated. This study included 4079 PTCs representing data from 23 studies. The results extracted from each study were split into two different groups, direct sequencing group or PCR group, based on the molecular "gold standard" method used to compare VE1 IHC staining. In the direct sequencing group, the IHC sensitivity was 100% (95% CI 0.97-1.00) and specificity 84% (95% 0.72-0.91). In the PCR group the sensitivity was 98% (95% CI 0.96-0.99) and specificity 89% (95% CI 0.82-0.94). Although immunohistochemical procedures varied by author, the overall performance of the VE1 clone shows that it is highly sensitive and relatively specific for detecting the BRAF V600E mutation in surgical resection specimens. However, standardization of immunohistochemical procedural method and scoring/interpretation criteria may improve the reliability and reproducibility for the use of VE1 clone for future practice.