DNA mismatch repair (MMR) status was considered to be a potential prognostic factor for colorectal cancer (CRC) but with conflicting reports, and varied in terms of TNM stages. Its relationship with prognosis in stage II-III CRC had not yet been systematically established. Therefore, we retrieved eligible studies published through May 2019, and screened out 51 studies that reported survival data (overall survival [OS] and/or disease-free survival [DFS]) in 28 331 CRC patients at stage II-III, totally 16.4% of whom were characterized as deficient MMR (dMMR). Significant associations of dMMR status were observed with longer OS (Hazard Ratio [HR] = 0.74, 95% CI: 0.68-0.82; P < .001), as well as DFS (HR = 0.67, 95% CI: 0.59-0.75, P < .001). However, dMMR patients received no statistically significant benefit from fluoropyrimidine-based treatment for either OS (HR = 0.84, 95%CI: 0.60-1.17; P = .31) or DFS (HR = 0.83, 95%CI: 0.60-1.15; P = .27), compared with that in proficient MMR (pMMR) patients for both OS (HR = 0.55, 95% CI: 0.43-0.71; P < .001) and DFS (HR = 0.60, 95% CI: 0.50-0.73; P < .001). Our analysis indicate that dMMR CRC patients at stage II-III had higher OS and DFS than pMMR ones, and fluoropyrimidine-based chemotherapy could improve survival in pMMR patients rather than dMMR ones.

Osteosarcoma (OS) is one of the most malignant tumors in children and young adults. To better understand the underlying mechanism, five related datasets deposited in the Gene Expression Omnibus were included in the present study. The Bioconductor 'limma' package was used to identify differentially expressed genes (DEGs) and the 'Weighted Gene Co‑expression Network Analysis' package was used to construct a weighted gene co‑expression network to identify key modules and hub genes, associated with OS. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes overrepresentation analyses were used for functional annotation. The results indicated that 1,405 genes were dysregulated in OS, including 927 upregulated and 478 downregulated genes, when the cut off value was set at a ≥2 fold‑change and an adjusted P‑value of P<0.01 was used. Functional annotation of DEGs indicated that these genes were involved in the extracellular matrix (ECM) and that they function in several processes, including biological adhesion, ECM organization, cell migration and leukocyte migration. These findings suggested that dysregulation of the ECM shaped the tumor microenvironment and modulated the OS hallmark. Genes assigned to the yellow module were positively associated with OS and could contribute to the development of OS. In conclusion, the present study has identified several key genes that are potentially druggable genes or therapeutics targets in OS. Functional annotations revealed that the dysregulation of the ECM may contribute to OS development and, therefore, provided new insights to improve our understanding of the mechanisms underlying OS.

Pathogenic mutations in breast cancer susceptibility genes BRCA1 and BRCA2 increase risks for breast, ovarian, fallopian tube, and peritoneal cancer in women; interventions reduce risk in mutation carriers.

The development of minimally invasive and low-cost assay enabling early diagnosis, treatment response and prognosis in cancer patients may provide a promising alternative to tumor biopsy. Circulating cell-free DNA (cfDNA) is probably the most promising tool among all components of liquid biopsy. This review includes studies exploring cfDNA as the diagnostic, prognostic or predictive biomarker for all types of cancer. In this article, we systematically reviewed the relevant literature from PubMed about cfDNA. All articles presented higher cfDNA concentration in cancer patients when compared with patients with benign disease or healthy individuals. Most of the articles showed a connection between cfDNA and prognosis. The presence of high cfDNA level in serum or plasma was associated with worse overall patient's survival. This review supports the idea that the cfDNA analysis represents a promising research area and hopefully in the future, could be applied as a new biomarker for cancer detection, prognosis determination and prediction of the response to therapy.

Multiple myeloma (MM) is a clonal plasma cell malignancy associated with hypercalcemia, bone lesions, and renal failure. The prognostic significance of the mutation of miRNAs, one kind of small noncoding RNA molecules that can modulate gene expression, should be confirmed in non-Hodgkin lymphomas (NHL). This study aimed to identify the prognostic value of miRNAs in patients with MM.

OBJECTIVE. The purpose of this study was to perform a systematic review and meta-analysis regarding CT features of non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement. MATERIALS AND METHODS. The PubMed and Embase databases were searched up to February 20, 2019. Studies that evaluated CT features of NSCLC with and without ALK rearrangement was included. Methodologic quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. The association between CT features and ALK rearrangement was pooled in the form of the odds ratio (OR) or the mean difference (MD) using the random-effects model. Heterogeneity was examined using the inconsistency index (I2). Publication bias was examined using funnel plots and Egger tests. RESULTS. Sixteen studies were included, consisting of 3113 patients with NSCLC. The overall prevalence of patients with ALK rearrangement was 17% (528/3113). Compared with NSCLC without ALK rearrangement, on CT images those with ALK rearrangement were more frequently solid (OR = 2.86), central in location (OR = 2.72), and 3 cm or smaller (OR = 0.57); had lower contrast-enhanced CT attenuation (MD = -4.79 HU); more frequently had N2 or N3 disease (OR = 5.63), lymphangitic carcinomatosis (OR = 3.46), pleural effusion (OR = 1.91), or pleural metastasis (OR = 1.81); and less frequently had lung metastasis (OR = 0.66). Heterogeneity varied among CT features (I2 = 0-80%). No significant publication bias was seen (p = 0.15). CONCLUSION. NSCLC with ALK rearrangement had several distinctive CT features compared with that without ALK rearrangement. These CT biomarkers may help identify patients likely to have ALK rearrangement.

Previous studies on associations of leptin receptor (LEPR) and peroxisome proliferator-activated receptor gamma (PPARG) polymorphisms with polycystic ovary syndrome (PCOS) yielded conflicting results.

We aimed to assess (1)-whether nuclear β-catenin is a marker of endometrial precancer, and (2)-the diagnostic accuracy of β-catenin immunohistochemistry in the differential diagnosis between benign and premalignant endometrial hyperplasia (EH), defining criteria for its use. Electronic databases were searched for studies evaluating β-catenin immunohistochemistry in normal endometrium (NE), benign and/or premalignant EH, and endometrioid carcinoma (EC). Odds ratio (OR; p < 0.05), sensitivity, specificity, diagnostic OR (DOR), positive and negative likelihood ratios (LR+, LR-) were calculated. Subgroup analyses were based on the classification system used (WHO or EIN) and criteria to define aberrant β-catenin expression (only nuclear or cytoplasmic/nuclear). Twelve studies with 1510 specimens were included. Nuclear β-catenin rate significantly increased from NE to benign EH (OR = 26.01; p = 0.0002, only in WHO subgroup), and from benign EH to premalignant EH (OR = 3.89; p = 0.0002; more markedly in EIN subgroup), but not from premalignant EH to EC (OR = 0.78; p = 0.29). Nuclear β-catenin accuracy was very low in WHO subgroup (sensitivity = 0.40, specificity = 0.76, LR+ = 1.85, LR- = 0.72; DOR = 2.89) and moderate in EIN subgroup (sensitivity = 0.19, specificity = 1.00, LR+ = 14.80, LR- = 0.83; DOR = 18.14). Cytoplasmic/nuclear β-catenin accuracy was absent in WHO subgroup (sensitivity = 0.45, specificity = 0.54, LR+ = 1.01, LR- = 1.01; DOR = 0.99) and low in EIN subgroup (sensitivity = 0.57, specificity = 0.86, LR+ = 3.63, LR- = 0.51; DOR = 8.30). Considering nuclear expression and using EIN system, β-catenin immunohistochemistry might be reliable as rule-in test for diagnosis of endometrial precancer, with perfect specificity and moderate overall accuracy.

The 5-yr survival of early-stage renal cell carcinoma (RCC) is approximately 93%, but once metastasised, the 5-yr survival plummets to 12%, indicating that early RCC detection is crucial to improvement in survival. DNA methylation biomarkers have been suggested to be of potential diagnostic value; however, their current state of clinical translation is unclear and a comprehensive overview is lacking.

The treatment of chronic myeloid leukaemia (CML) requires quantitative polymerase chain reaction (qPCR) to monitor BCR-ABL1 in International Scale (IS). Some normal subjects were found to harbour BCR-ABL1. We performed a systematic review on normal subjects harbouring BCR-ABL1. A literature search was done on July 16, 2017 using EBSCOhost Research Databases interface and Western Pacific Region Index Medicus. Two authors selected the studies, extracted the data, and evaluated the quality of studies using the modified Appraisal Tool for Cross-Sectional Studies independently. The outcomes were prevalence, level of BCR-ABL1IS, proportion, and time of progression to CML. The initial search returned 4,770 studies. Eleven studies, all having used convenient sampling, were included, with total of 1,360 subjects. Ten studies used qualitative PCR and one used qPCR (not IS). The mean prevalence of M-BCR was 5.9, 15.5, and 15.9% in cord blood/newborns/infants (CB/NB/I) (n = 170), children (n = 90), and adults (n = 454), respectively, while m-BCR was 15, 26.9, and 23.1% in CB/NB/I (n = 786), children (n = 67), and adults (n = 208), respectively. No study reported the proportion and time of progression to CML. Nine studies were graded as moderate quality, one study as poor quality, and one study as unacceptable. The result of the studies could neither be inferred to the general normal population nor compared. Follow-up data were scarce.

Previous investigations yielded inconsistent results for the associations between pancreatic cancer (PC) risk and genetic polymorphisms. The study aimed to perform a systematic review and meta-analysis of studies exploring association of some genetic polymorphisms and PC risk.

Colorectal cancer (CRC) represents the third-most common cancer worldwide and one of the main challenges for public health. Despite great strides in the application of neoadjuvant and adjuvant therapies for rectal and colon cancer patients, each of these treatments is still associated with certain adverse effects and different response rates. Thus, there is an urgent need for identifying novel potential biomarkers that might guide personalized treatments for specific subgroups of patients. However, until now, there are no biomarkers to predict the manifestation of adverse effects and the response to treatment in CRC patients. Herein, we provide a systematic review of epidemiological studies investigating epigenetic biomarkers in CRC patients receiving neoadjuvant or adjuvant therapy, and their potential role for the prediction of outcomes and response to treatment. With this aim in mind, we identified several epigenetic markers in CRC patients who received surgery with adjuvant or neoadjuvant therapy. However, none of them currently has the robustness to be translated into the clinical setting. Thus, more efforts and further large-size prospective studies and/or trials should be encouraged to develop epigenetic biomarker panels for personalized prevention and medicine in CRC cancer.

Background The prognostic value of Chemokine (C-X-C motif) ligand 1 (CXCL1) in various types of cancer remains controversial. Here we aimed to evaluate the prognostic role of CXCL1 for cancer. Methods A comprehensively search of the PubMed, Embase, Web of Science, Wanfang and China National Knowledge Internet databases was conducted to retrieve eligible studies meeting the inclusion criteria. Overall survival (OS), progression-free survival (PFS) and various clinicopathological parameters were defined as endpoints. Stata SE12.0 software was used for quantitative meta-analysis. Results A total of 17 studies encompassing 2265 cancer patients were included. Our meta-analysis showed that patients with higher CXCL1 expression had significantly shorter OS, according to both multivariate (HR 1.51, 95% CI 1.19-1.83, P < .01) and univariate analysis (HR 2.08, 95% CI 1.62-2.54, P < .01). Furthermore, higher CXCL1 expression was significantly correlated with advanced TNM stage and lymph node metastasis (both P < .05). Conclusions High CXCL1 expression is a risk factor for cancer prognosis indicating a poor OS, and advanced TNM stage and lymph node metastasis, demonstrating that it may be a promising prognostic biomarker for different cancers.

Pancreatic adenocarcinoma is the third most common cause of cancer death among men and women in the United States.

Associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity have been reported. To consolidate the results from all available reports in scientific databases, systematic review and meta-analysis techniques were used to quantify these associations. Studies investigating associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity were systematically searched in PubMed, Human Genome Epidemiology Network, and the Cochrane Library. Primary outcomes were the associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity. Overall odds ratios (ORs) with the corresponding 95%CIs were calculated using a random-effect model to determine the associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity. A clear association between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity was identified in our analyses. The summary OR was 6.23 (95%CI = 4.11-9.45). Similar associations were also found in the subgroup analyses by lapatinib treatment regimens. ORs were 10.04 (95%CI = 6.15-16.39), 8.65 (95%CI = 4.52-16.58), and 3.88 (95%CI = 2.20-6.82) in the lapatinib group, lapatinib + trastuzumab group, and lapatinib + chemotherapy or lapatinib + trastuzumab + chemotherapy group, respectively. Since HLA-DRB1*07:01 is associated with lapatinib-induced hepatotoxicity, genetic screening of HLA-DRB1*07:01 in breast cancer patients prior to lapatinib therapy is warranted for patient safety. In addition, further studies should define the risk of HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity in specific ethnicities.

Piles of evidence have supported the relationship between miR-618 rs2682818 polymorphism and tumorigenesis, but the conclusion remains inconsistent. In the present study, we conducted a meta-analysis to sniff out the potential risk between miR-618 rs2682818 and overall cancers. Crude odds ratios (ORs) and 95% confidence intervals (CIs) analyzed by Z-test were employed to estimate the potential interrelation in five genetic models. We also prospected how the rs2682818 affects the second structure of miR-618. Finally, 10 independent studies meet the enrolled criteria, along with 4099 cancer cases and 5057 healthy controls. Overall, no exceeding interrelation was sniffed out in the pooled data among five inherited models, as well as stratified analyses. Whereas, the enhanced cancer risk of miR-618 rs2682818 variant stratified by breast cancer was revealed, in heterozygote genetic model (AC vs. CC: OR = 1.291, 95%CI = 1.012-1.648, P = 0.040) and dominant contrast model (AA + AC vs. CC: OR = 1.280, 95%CI = 1.009-1.623, P = 0.042). The second structure prediction result shown that the mutant A allele might change the first stem-loop of miR-618, and the free energy of it would turn from -39.1 to -35.1 kcal/mol. All in all, our meta-analysis had successfully chased down that miR-618 rs2682818 polymorphism is not linked with overall cancer risk, but in the dominant genotype of breast cancer.

BACKGROUND This meta-analysis aimed to clarify the diagnostic role of plasma methylated SEPT9 (mSEPT9) in colorectal cancer (CRC) and examined its association with CRC. MATERIAL AND METHODS A systematic review was conducted prior to July 2018. Summary sensitivity, specificity, and positive and negative likelihood ratio (PLR/NLR) were calculated for the diagnostic value of mSEPT9 for CRC. The areas under the receiver operating curves (AUCs) were used to summarize the overall test performance. RESULTS Twenty-two studies with 2271 CRC patients were enrolled. The summary sensitivity, specificity, PLR, NLR, DOR, and AUC of the overall analysis of mSEPT9 were 0.69, 0.92, 8.1, 0.34, 24, and 0.89, respectively. Subgroup and meta-regression analyses demonstrated that the diagnostic value was higher for the Epi proColon 2.0 assay, Asian ethnicity, and mSEPT9 test combined with fecal occult blood test (FOBT) or fecal immunochemical test (FIT) than for other test methods, white ethnicity, and mSEPT9 test alone. The rate of mSEPT9 positivity was higher in advanced CRC cases compared with early-stage CRC cases, and was higher in CRC cases than in adenoma cases. No significant difference in mSEPT9 positivity rate was found between left- and right-sided CRC. CONCLUSIONS Plasma mSEPT9 has a high diagnostic value for CRC, especially on the newly developed Epi proColon test 2.0 method. The diagnostic sensitivity is superior among Asians compared to whites, and the combination of mSEPT9 and FOBT/FIT has a better performance than mSEPT9 alone. Finally, the expression of mSEPT9 is associated with CRC stage but not with location.

Mendelian randomization (MR) analyses have been increasingly used to seek evidence of causal associations. This systematic review aims at characterizing and evaluating the reporting of MR analyses in oncological studies.

Female BRCA1 and BRCA2 mutation carriers have an increased lifetime risk of developing breast and/or ovarian cancer. Hence, they face the difficult decision of choosing a preventive strategy such as risk-reducing surgeries or intensified breast screening. To help these women during their decision process, several patient decision aids (DA) were developed and evaluated in the last 15 years. Until now, there is no conclusive evidence on the effectiveness of these DA. This study aims 1) to provide the first systematic literature review about DA addressing preventive strategy decisions for female BRCA1 and BRCA2 mutation carriers, 2) to analyze the quality of the existing evidence, 3) to evaluate the effects of DA on decision and information related outcomes, on the actual choice for preventive measure and on health outcomes.