Since the first description of the natural history of chronic lymphocytic leukemia (CLL) by David Galton in 1966, the considerable heterogeneity in the disease course has been well recognized. The Rai and Binet staging systems described ∼40 years ago have proven to be robust prognostic tools. Over the past 2 decades, several novel biological, genetic, and molecular markers have been shown to be useful adjuncts to the Rai and Binet staging systems. In this systematic review, we examined the role of immunoglobulin heavy-chain variable region gene (IGHV) mutation status and genetic abnormalities determined by interphase fluorescence in situ hybridization (FISH) in patients with newly diagnosed CLL. The cumulative evidence presented in this systematic review is sufficient to recommend that FISH and IGHV be performed as standard clinical tests for all patients with newly diagnosed CLL in those countries with the resources to do so. In addition to clinical stage, these parameters could represent the minimal standard initial prognostic evaluation for patients with CLL. This approach will allow the application of powerful, recently developed prognostic indices (all of which are dependent on IGHV and FISH results) to all patients with newly diagnosed CLL.

The individual response to targeted tyrosine kinase inhibitors (TKIs) in the treatment of metastatic renal cell cancer (mRCC) is highly variable. Outlined in this article are findings on potential biomarkers for TKI treatment outcome in mRCC and an evaluation of the status of clinical implementation.

The Hedgehog (Hh) signaling pathway has recently been reported to be associated with the prognosis of digestive system cancers. However, the results are inconsistent.

Genetic predisposition for childhood cancer is under diagnosed. Identifying these patients may lead to therapy adjustments in case of syndrome-related increased toxicity or resistant disease and syndrome-specific screening programs may lead to early detection of a further independent malignancy. Cancer surveillance might also be warranted for affected relatives and detection of a genetic mutation can allow for reproductive counseling. Here we present an easy-to-use selection tool, based on a systematic review of pediatric cancer predisposing syndromes, to identify patients who may benefit from genetic counseling. The selection tool involves five questions concerning family history, the type of malignancy, multiple primary malignancies, specific features and excessive toxicity, which results in the selection of those patients that may benefit from referral to a clinical geneticist.

Basic fibroblast growth factor (bFGF) is known to stimulate angiogenesis and thus to influence the proliferation, migration and survival of tumor cells. Many studies examined the relationship between human bFGF overexpression and survival in lung cancer patients, but the results have been mixed. To systematically summarize the clinical prognostic function of bFGF in lung cancer, we performed this systematic review with meta-analysis.

Metastatic colorectal cancer (mCRC) tumours harbouring a RAS mutation are associated with a lack of treatment benefit from anti-EGFR monoclonal antibodies (mAbs). However, observational evidence has led to speculation that mCRC patients with KRAS G13D mutant (MT) tumours may derive a benefit from treatment with anti-EGFR mAbs.

One of the most significant risk factors for the development of ovarian cancer (OC) is a genetic mutation in BRCA1 (breast cancer gene 1) or BRCA2. Here we describe the impact of previous and current guidance on BRCA testing practices and provide evidence about which characteristics best identify patients with OC and an underlying germline BRCA mutation.

Short noncoding RNAs known as microRNAs (miRNAs) control protein expression through the degradation of RNA or the inhibition of protein translation. The miRNAs influence a wide range of biologic processes and are often deregulated in cancer. This family of small RNAs constitutes potentially valuable markers for the diagnosis, prognosis, and therapeutic choices in prostate cancer (PCa) patients, as well as potential drugs (miRNA mimics) or drug targets (anti-miRNAs) in PCa management.

Previous studies have revealed that the expression level of microRNA-29a (miR-29a) was remarkably different in colorectal cancer (CRC) patients and healthy controls, indicating that miR-29a can be used as a diagnostic marker of CRC, but the results have been inconsistent. We conducted this meta-analysis to assess the diagnostic performance of blood-based miR-29a for CRC. We performed a systematic review of studies published over the past two decades to investigate the diagnostic performance of serum miR-29a for the diagnosis of CRC. QUADAS-2 was used to evaluate the quality of the studies. Performance characteristics (diagnostic sensitivity, specificity, and other measures of accuracy) were pooled and examined using random-effect models. Five studies, which included 281 CRC patients and 299 healthy controls, met the inclusion criteria. The summary estimates for miR-29a in CRC diagnoses showed a diagnostic sensitivity of 0.59 (95%CI = 0.53-0.65), a specificity of 0.89 (95%CI = 0.85-0.93), and a diagnostic odds ratio of 12.22 (95%CI = 5.07-29.44). The area under curve and Q value for the summary receiver operating characteristic curves were 0.9128 and 0.8453, respectively. In conclusion, miR-29a may be a novel potential biomarker for CRC diagnosis.

Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of CRC-related liver metastases (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status.

Consistency of procedures for the evaluation of a predictive biomarker (including sample collection, processing, assay and scoring system) based on adequate evidence is necessary to implement research findings in clinical practice. As a case study we evaluated how a particular predictive biomarker, ERCC1, was assessed in research on platinum-based chemotherapy in non-small-cell lung cancer and what motivated the choice of procedure.

The aim was to systematically review the characteristics of ovarian cancer in women with Lynch syndrome (LS) and evaluate the role of surveillance in detection of ovarian cancer in LS.

The prognostic significance of KIT mutations in core-binding factor acute myeloid leukemia (CBF-AML), including inv(16) and t(8;21) AML, is uncertain. We performed a systematic review and meta-analysis of the effect of KIT mutations on the complete remission (CR) and relapse rates and overall survival (OS) of CBF-AML. PubMed, Embase, Web of Science, and the Cochrane Library were searched and relevant studies were included. Negative effect was indicated on relapse risk of CBF-AML (RR [relative risk], 1.43; 95%CI [confidence interval], 1.20-1.70) and t(8;21) AML (RR, 1.70; 95% CI, 1.31-2.21), not on OS of CBF-AML (RR, 1.09; 95% CI, 0.97-1.23), CR (OR [odds ratio], 0.95; 95% CI, 0.52-1.74), relapse risk (RR, 1.12; 95% CI, 0.90-1.41) or OS (RR, 1.03; 95% CI, 0.90-1.18) of inv(16) AML. Subgroup analysis of t(8,21) AML showed negative effect of KIT mutations on CR (OR, 2.03; 95%CI: 1.02-4.05), relapse risk (RR, 1.89; 95%CI: 1.51-2.37) and OS (RR, 2.26; 95%CI: 1.35-3,78) of non-Caucasians, not on CR (OR, 0.61; 95%CI: 0.19-1.95) or OS (RR, 1.12; 95%CI: 0.90-1.40) of Caucasians. This study indicates KIT mutations in CBF-AML to be included in the initial routine diagnostic workup and stratification system of t(8,21) AML. Prospective large-scale clinical trials are warranted to evaluate these findings.

Nestin has been identified as a molecular marker of neural progenitor cells and putative glioma stem cells (GSCs). Various studies examining the relationship between nestin expression with the clinical outcome in glioma patients have yielded inconclusive results. Thus, we conducted a systematic review to evaluate the association of nestin with prognosis and clinicopathological features of glioma patients. The electronic searches were performed through the database of PubMed, MEDLINE, Embase, and CNKI. In total, this meta-analysis included 14 studies covering 897 nestin + cases and 704 controls. The correlation between nestin expression and clinicopathological or prognostic parameters was evaluated by Stata 11.0 software. Our results showed that nestin protein abundance was significantly correlated with the histological grade [odds ratio (OR) = 4.36, 95 % confidence interval (CI) = 2.14-8.88, P = 0.003] of glioma. With respect to prognosis, nestin expression was positively correlated with overall survival (OS) [hazard ratio (HR) = 1.98, 95 % CI = 1.30-3.02, P = 0.000] and progression-free survival (PFS) (HR = 1.90, 95 % CI = 1.18-3.07, P = 0.040). The further stratified analysis not only defined the predictive function of nestin in different ages but also revealed that different antibodies did not alter the positive outcomes and higher standard cutoff values were more suitable for the accurate assay of nestin. Taken together, our results indicate that nestin may play an important role in the prediction of the clinicopathology and poor prognosis of glioma patients. This study should be taken into consideration in the development of new diagnostic and therapeutic programs.

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer deaths. Erlotinib is the first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), the National Comprehensive Cancer Network (NCCN) guidelines recommend it as a first-line agent in patients with sensitizing EGFR mutations.We conducted a meta-analysis to compare the efficacy of erlotinib and chemotherapy for advanced NSCLC, and evaluated the efficacy of them to provide references for further clinical practice and research.PubMed, EMBASE, CBM, CNKI, WanFang database, The Cochrane library, and Web of Science, as well as abstracts presented at ASCO conferences and ClinicalTrials.gov were searched to identify relevant studies. HR with 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS), relative risk (RR) with 95% CIs for objective response rate (ORR) and 1-year survival rate (OSR) were all extracted. If the I was ≤40%, then the trial was considered to be heterogeneous, and a fixed-effects model was selected. Otherwise, a random-effects model was used. Meta-regression and sensitivity analyses were conducted to determine the possible heterogeneity causes and to further identify the influence of the various exclusion criteria on the overall risk estimate.The pooled analysis demonstrated a PFS HR of 0.93 (95% CI = 0.73, 1.19) for erlotinib versus chemotherapy and an ORR of 18.43% versus 22.07%, respectively. The OS HR was 1.02 (95%CI = 0.93, 1.12). The HRs for PFS estimated based on 10 trials involving 1101 patients were 0.22 (95% CI = 0.15, 0.29) and 1.27 (95% CI = 1.04, 1.48) in EGFR mutation-type and wild-type patients, respectively. The HRs for OS calculated from 4 studies including 681 participants were 0.83 (95% CI = 0.61, 1.05) and 0.86 (95% CI = 0.68, 1.04) in EGFR mutation-type and wild-type patients, respectively. The 1-year survival rates were 31.31% and 32.41%, respectively.Overall, the present meta-analysis suggested that erlotinib did not improve the ORR, PFS, OS or the 1-year survival rate for whole patients. However, erlotinib could benefit patients with EGFR mutation in terms of PFS, but the OS does not benefit from it for these patients. Further studies of erlotinib for these subgroup patients are warranted.

To clarify the prognostic role of tumour protein 53 (TP53) mutations in patients with oesophageal adenocarcinoma (OAC) as there is a need for biomarkers that assist in guiding management for patients with OAC.

The prognostic value of the telomerase reverse transcriptase (TERT) promoter mutation, resulting in poor clinical outcomes of papillary thyroid carcinoma (PTC), has been generally confirmed. To data, there is no high-level evidence approving the association of TERT promoter mutation and aggressive clinical behaviours in PTC. To systematically evaluate it, a systematic review and meta-analysis of the published literatures were carried out.

To date, many studies have reported that microRNAs participate in human carcinogenesis as tumor suppressors or oncogenes and may play important roles as prognostic biomarkers of cancer. The aim of this meta-analysis was to assess the prognostic value of circulating miR-125 in human malignant neoplasms by summarizing the results from all available studies.

Extensive epidemiological studies have demonstrated that there are associations between variants in intron 2 of FGFR2 and the breast cancer risk in various populations; however, the relationships are not yet conclusively established. To comprehensively review the epidemiological studies showing associations between the variants of FGFR2 and the breast cancer risk, and to establish correlations via a meta-analysis. The PubMed and MEDLINE databases were searched for eligible studies. The associations between the variants and breast cancer risk were evaluated using a random-effects model. The heterogeneity among the studies and the potential publication bias were also evaluated. Fifty-three studies with a total of 121,740 cases and 198,549 controls have examined the associations between 23 variants in intron 2 of FGFR2 and the breast cancer risk. The relationships for the 10 most frequently evaluated variants-rs1078806, rs11200014, rs1219648, rs2420946, rs2981578, rs2981579, rs2981582, rs3135718, rs10736303, and rs3750817-were synthesized based on a meta-analysis. Interestingly, we found that all 10 variants were significantly associated with the risk of breast cancer. In studies stratified by ethnicity, we found that the associations were more notable in Caucasians and Asians compared to Africans. Similar pooled results were found in population-based and hospital-based case-control studies and in studies with small and large sample sizes. FGFR2 is a breast cancer susceptibility gene, and various variants of FGFR2 are significantly associated with the breast cancer risk. However, the biological mechanisms underlying the associations need to be elucidated in future studies.

A DNA repair protein, X-ray repair cross-complementing group 1 (XRCC1), has been implicated in the development of multiple cancers, including non-Hodgkin lymphoma (NHL). Recent studies evaluating the association between XRCC1 polymorphisms and NHL risk have been published. However, the published studies are controversial. This systematic review and meta-analysis of case-control studies aimed to evaluate the association between three single nucleotide polymorphisms (SNPs) of XRCC1, Arg194Trp, Arg280His and Arg399Gln, with risk for developing NHL. We conducted a comprehensive literature search using PubMed, Embase, and the Cochrane Library databases for relevant studies regarding the association between XRCC1 SNPs and NHL risk. Thirteen published case-control studies involving the Arg194Trp (3897 cases and 5371 controls), Arg280His (2140 cases and 3158 controls) and Arg399Gln (2722 cases and 4856 controls) SNPs were selected for meta-analysis. The Arg194Trp SNP was associated with increased NHL risk within the Asian population, and increased diffuse large B cell lymphoma (DLBCL) risk within the overall population under dominant model. The Arg399Gln SNP was associated with decreased risk for NHL and DLBCL under heterozygous and dominant models of inheritance. The Arg280His SNP was not associated with NHL risk by overall or subgroup analyses.