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.

Previous studies have reported that miR-196a is upregulated in cervical cancer tissues and cell lines. However, whether serum miR-196a is increased in patients with cervical cancer or cervical intraepithelial neoplasia (CIN), and its potential clinical value remained unknown. In total, 105 cervical cancer patients, 86 CIN patients, and 50 healthy volunteers were recruited. Quantitative reverse transcription-polymerase chain reaction was performed to compare the serum levels miR-196a in all participants. The associations between serum miR-196a and CIN grade/clinicopathological parameters of cervical cancer were also examined. A survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were conducted to explore the independent risk factors for cervical cancer. Our results revealed that serum miR-196a levels were higher in patients with cervical cancer (P < 0.01) and CIN (P < 0.05) compared to those in healthy controls. Serum miR-196a was associated with CIN grade and various cervical cancer parameters including tumor size (P = 0.031), lymph node metastasis (P = 0.018), FIGO stage (P = 0.004), and grade (P = 0.011). Cervical cancer patients with higher serum miR-196a levels had a poorer overall survival rate (P = 0.004). Multivariate analysis revealed that high serum miR-196a was an independent predictor for poor survival of cervical cancer (HR = 3.510; 95%CI = 1.961-6.874; P = 0.025). In conclusion, our findings suggest that serum miR-196a overexpression is associated with CIN grade and cervical cancer progression. Therefore, serum miR-196a may be a reliable biomarker for early detection and prognosis of cervical cancer.

Breast cancer is the most common gynecologic tumor globally that threatens women's health. Lipoic acid is a type of antioxidant that can alleviate oxidative stress damage. Studies showed that lipoic acid could inhibit the proliferation of tumor cells in cervical cancer and colon cancer. This paper intends to explore the combined effect of lipoic acid and paclitaxel on breast cancer cells. Breast cancer MCF-7 cells were divided into four groups: control group, lipoic acid group, paclitaxel group, and a combination group. MTT was applied to detect the drugs' influence on breast cancer cell proliferation. A colony formation test was used to determine the effects on breast cancer cell clone formation rate. Western blot was performed to detect the effects on nuclear factor (NF)-κB. Lipoic acid alone can inhibit tumor cell proliferation and clone formation with time dependence. Compared with the control, paclitaxel alone can significantly suppress tumor cell proliferation and clone formation (P < 0.05). Lipoic acid and paclitaxel in combination obviously strengthened their individual inhibitory effects on tumor cells (P < 0.05). Compared with the paclitaxel alone group, the combination group exhibited more remarkable inhibitory effect (P < 0.05). Lipoic acid alone or combined with paclitaxel can inhibit NF-κB expression and inhibit breast cancer cell proliferation.

Dysregulated miR-125 observed in multiple cancer types has suggested that it is involved in malignant proliferation and invasion. However, the clinical significance of miR-125 in human breast cancer (BC) has not yet been fully elucidated. In the present study, the expression of miR-125a-5p/3p and miR-125b in 143 pairs of BC and normal adjacent tissues (NATs) was measured by real-time quantitative PCR, and the correlation between expression and clinicopathological features was explored. miR-125a-5p and miR-125b were significantly down-regulated in BC tissue samples compared with their matched NAT samples, while the difference in miR-125a-3p expression between BC tissues and NATs was not statistically significant. The expression level of miR-125a-5p was found to be significantly higher in younger patients (<35 years) than in older patients (≥35, P = 0.005). When the patients were divided into three groups according to age (<35, 36-48, and ≥48 years), a gradual reduction in miR-125a-5p expression was observed in BC tissue samples that correlated to increases in age (P = 0.009). There were no significant correlations between miR-125 expression and other clinicopathological features including tumor size, histological grade, hormone receptor status, Her-2 status, and lymph node metastasis. Taken together, these findings suggest that miR-125a-5p may play an important role in BC progression in an age-dependent manner, and that the down-regulation of miR-125a-5p and miR-125b may serve as independent predictors for breast cancer.

The specific correlation between CXCR4 expression and survival in non-small cell lung cancer (NSCLC) has been investigated independently; however, these have yielded inconsistent results. Therefore, we examined the exact relationship between CXCR4 expression and NSCLC in this meta-analysis. The bibliographic databases in English and Chinese were carefully searched and data regarding the prognostic value of CXCR4 and its association with pathological parameters of NSCLC were collected. Pooled odds ratios (OR) with 95% confidence interval (CI) were applied. A total of twelve studies (CXCR4 positive cases = 565, CXCR4 negative = 755; 2003-2013) that matched our predefined criteria were finally incorporated into our study. The pooled OR revealed that expression of CXCR4 in NSCLC patients was apparently correlated with lymphatic metastasis, distant metastasis, and TNM stages (lymphatic metastasis: OR = 1.91, 95%CI = 1.21-3.27, P = 0.018; distant metastasis: OR = 4.81, 95%CI = 1.69-13.66, P = 0.003; TNM stages: OR = 3.91, 95%CI = 1.22-12.55, P = 0.022). Positive expression of CXCR4 was also strongly correlated with a shorter overall survival (OS) rate in NSCLC patients (hazard ratio = 2.10, 95%CI = 1.21-2.99, P < 0.05). Further stratification by ethnicity indicated a negative association between CXCR4 expression and NSCLC development and prognosis in Asians NSCLC patients in all four models (P < 0.05). This indicated that elevated CXCR4 expression may be correlated with aggressive metastasis, advanced TNM stages, and shorter OS rate in NSCLC patients, suggesting a poor prognostic outcome of this disease.

Many epidemiological studies have shown the association between certain genetic variations in the Toll-like receptor 4 (TLR4) gene (for example, rs4986790 and rs4986791) and cancer risk. However, the results from investigations into the association between rs11536889, a genetic variant in the 3'-untranslated region of TLR4, and cancer risk lack consensus. We performed a meta-analysis to investigate the effect of rs11536889 on cancer risk. A total of 12 relevant case-control studies were included in this analysis (6222 cases and 7948 controls). The pooled ORs with their corresponding 95%CIs were estimated. We did not detect any association between rs11536889 and overall cancer risk (P = 0.13). However, stratification analysis by cancer type revealed a borderline statistically significant increased risk in both genotype comparison (OR for the variant genotype in the dominant model = 1.17; 95%CI = 0.98-1.40; P = 0.08) and allele comparison (OR for variant allele = 1.14; 95%CI = 0.99-1.32; P = 0.07) for prostate cancer. In contrast, no statistically significant or borderline result was found for gastric cancer. These findings indicate that rs11536889 in TLR4 might be specifically associated with prostate cancer. However, owing to the modest and underpowered results, and the limitations of the original studies included for analysis, further prospective studies with larger sample sizes are required to confirm our findings.

We evaluated the associations between three common polymorphisms in the AGER gene and the risks of breast (BC) and lung (LC) cancer using meta-analysis. A systematic electronic search of the literature was conducted to identify all potential correlation studies in Embase, Web of Science, Cochrane Library, CINAHL, PubMed, CISCOM, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases. Five case-control studies that investigated the correlation of AGER gene polymorphisms with BC and LC were included in the meta-analysis, representing 4337 subjects. An increased frequency of the AGER rs1800625 T>C polymorphism was observed in patients with either BC or LC. We found that the frequencies of AGER rs1800624 T>A and rs2070600 G>A variants were positively related to the risks of BC and LC under allelic models, but that these relationships were not detected under dominant models. Disease-stratified results under allelic models demonstrated that the frequencies of the AGER rs1800625 T>C and rs2070600 G>A polymorphisms were positively correlated with the susceptibility to LC, while the same correlations were not found in BC. Further subgroup analysis by genotyping method indicated that the rs1800624 T>A variant was associated with increased risks of BC and LC under a dominant model in both non-polymerase chain reaction-restriction fragment length polymorphism (non-PCR-RFLP) and PCR-RFLP subgroups. In conclusion, these data indicated that common polymorphisms in the AGER gene might increase the risks of BC and LC.

The PAX5 gene, which encodes the B-cell specific activator protein, is one of the most important factors in determination of B-cell development. This gene is the main target of somatic mutations in acute B lymphoblastic leukemia (B-ALL). For example, point mutations, deletions, as well as other gene rearrangements may lead to several forms of B-cell malignancy. In this study, we obtained 50 blood samples from patients diagnosed with ALL, and screened for PAX5 mutations using sequencing in exons 1, 2 and 3. We found a heterozygous germline variant, c.113G>A (p.Arg38His), which affects the paired domain of PAX5. It seems that this mutation is pathogenic, but is recessive. Our findings suggest that this mutation in a single allele of the PAX5 gene is not sufficient to cause disease, and it is possible that other alleles are also involved in the onset of B-ALL.

Despite recent advances in osteosarcoma diagnosis and therapy, much remains unclear about the molecular mechanisms involved in the disorder, and the discovery of novel drug-targeted genes is essential. We explored the potential molecular mechanisms and target genes involved in the development and progression of osteosarcoma. First, we identified the differentially expressed genes in osteosarcoma patients and matching normal controls. We then constructed a differential expression network based on differential and non-differential interactions. Pathway-enrichment analysis was performed based on the nodes contained in the main differential expression network. Centrality analysis was used to select hub genes that may play vital roles in the progression of human osteosarcoma. Our research revealed a total of 176 differentially expressed genes including 82 upregulated and 94 downregulated genes. A differential expression network was constructed that included 992 gene pairs (1043 nodes). Pathway-enrichment analysis indicated that the nodes in the differential expression network were mainly enriched in several pathways such as those involved in cancer, cell cycle, ubiquitin-mediated proteolysis, DNA replication, ribosomes, T-cell receptor signaling, spliceosomes, neurotrophin signaling, oxidative phosphorylation, and tight junctions. Six hub genes (APP, UBC, CAND1, RPA, YWHAG, and NEDD8) were discovered; of these, two genes (UBC and RPA) were also found to be disease genes. Our study predicted that UBC and RPA had potential as target genes for the diagnosis and treatment of osteosarcoma.

It is well known that chemokine receptors and their ligands play important roles in mediating the invasion and metastasis of malignant tumors. This aim of this study was to investigate the expression and clinical significance of chemokine receptor CXCR4 and its ligand CXCL12 in bladder tumor tissues. Cancerous and adjacent normal bladder tissues were collected from 42 patients. The expressions of CXCR4 and CXCL12 proteins were then detected by immunohistochemistry, and the expressions of CXCR4 and CXCL12 mRNAs were detected by RT-PCR. Bladder cancer tissues showed higher positive expressions of CXCR4 and CXCL12 than those in normal bladder mucosal tissues (z = 7.332, 6.758, P < 0.001). Positive expressions of CXCR4 and CXCL12 were related to the differentiation degree and invasive depth of cancer tissues (z = 2.598-4.594, P < 0.05), but not to patient gender or age (z = 0.273-0.554, P > 0.05). The expression of CXCR4 was positively correlated to CXCL12 expression in bladder cancer tissues (r = 0.661, P < 0.05). RT-PCR revealed that CXCR4 and CXCL12 mRNAs were not expressed in normal tissues. Moreover, with increased depth of invasion, CXCR4 and CXCL12 mRNA expressions gradually increased in bladder cancer tissues and showed significant intergroup differences (F = 56.642, 67.928, P < 0.01). Taken together, these results indicate that the chemokine receptor CXCR4 and its ligand CXCL12 play important roles in the occurrence and development of bladder cancer.

MicroRNA-34a (miR-34a) has been found to be downregulated in esophageal squamous cell carcinoma (ESCC) tissues compared with that in normal tissues (P < 0.05), and miR-34a overexpression increased apoptosis and decreased clonogenic formation. However, the clinical significance and prognostic value of miR-34a in ESCC has not yet been investigated. In total, 111 patients with ESCC diagnosed and treated at the Department of Thoracic Surgery of Fujian Provincial Hospital between March 2008 and February 2014 were included in this retrospective study. Quantitative real-time PCR was performed to detect expression levels of miR-34a. The associations between miR-34a expression and clinicopathological features were analyzed using χ(2) tests. For analysis of survival data, Kaplan-Meier curves were constructed, and the log-rank test was performed. The expression levels of miR-34a in ESCC tissues were significantly decreased (P < 0.01), compared with those in adjacent normal esophageal tissues. Low miR-34a expression in ESCC tissues was significantly associated with tumor differentiation (P = 0.013), lymph node status (P = 0.038), and advanced clinical stage (P < 0.001). The Kaplan-Meier analysis and log-rank test revealed that low miR-34a levels had a significant impact on overall survival of patients with ESCC (P = 0.006). Multivariate analyses showed that the expression of miR-34a was an independent prognostic factor for ESCC (P = 0.018). Our findings indicate that there is reduced expression of miR-34a in human ESCC tissues and suggest a crucial role for miR-34a downregulation in ESCC progression and prognosis.

Based on gene expression, we have classified 53 colon cancer patients with UICC II into two groups: relapse and no relapse. Samples were taken from each patient, and gene information was extracted. Of the 53 samples examined, 500 genes were considered proper through analyses by S-Kohonen, BP, and SVM neural networks. Classification accuracy obtained by S-Kohonen neural network reaches 91%, which was more accurate than classification by BP and SVM neural networks. The results show that S-Kohonen neural network is more plausible for classification and has a certain feasibility and validity as compared with BP and SVM neural networks.

We performed a study to investigate the role of ERCC1 (rs11615, rs2298881, and rs3212986) and ERCC2 (rs13181, rs238406, and rs1799793) polymorphisms in the prognosis of gastric cancer. A total of 346 patients with gastric cancer were recruited between May 2009 and May 2012. Single nucleotide polymorphism genotyping was performed using the Sequenom MassARRAY platform. The GA+AA genotype of ERCC2 rs1799793 showed significant and favorable response to chemotherapy than the wide-type GG genotype in multivariate analysis (OR = 1.78, 95%CI = 1.13-2.81). In a Cox proportional hazard model, carriers of ERCC2 rs1799793 GA+AA genotype exhibited longer duration of survival than did those with the GG genotype (hazards ratio = 0.57, 95%CI = 0.35-0.92). In conclusion, our study suggests that ERCC2 rs1799793 polymorphic variation could be used as a predictor for the prognosis of gastric cancer.

We evaluated the influence of the vascular endothelial growth factor (VEGF) -C936T polymorphism on prognosis of hepatocellular carcinoma (HCC), cirrhosis, and hepatitis C virus (HCV) infection. Serum VEGF and alpha-fetoprotein (AFP) levels were determined and used to characterize sensitivity and specificity. A total of 285 subjects were studied: 68 HCC, 118 cirrhosis, 43 HCV, and 56 healthy controls. Prevalence of the VEGF -C936T polymorphism and serum levels of VEGF and AFP were analyzed by polymerase chain reaction-restriction fragment length polymorphism and enzyme-linked immunosorbent assay, respectively. The genotype CC (frequencies between 63.24 and 76.79%; P > 0.05) and the C allele (absolute frequencies from 0.816 to 0.884, P > 0.05) were prevalent in all groups. Higher VEGF levels in HCC patients (588.0 ± 501.0 pg/mL) were observed, particularly in patients with the T allele in VEGF -C936T (764.4 ± 571.7 pg/mL) compared to those in the other groups (P < 0.05). The same trend occurred with AFP levels (HCC = 8.522 ± 23.830; cirrhosis = 12.7 ± 59.3; HCV = 4.6 ± 4.7; control = 2.7 ± 1.8 ng/mL; P = 0.005). Levels of VEGF and AFP showed sensitivity of 65 and 28% and specificity of 85 and 99%, respectively, for HCC patients. In conclusion, the VEGF -C936T polymorphism is not associated with HCC but the mutant allele (T) increases VEGF levels in HCC patients. VEGF could be a potential biomarker for HCC, while AFP could be used to distinguish between patients with HCC and cirrhosis or HCV.

Mitochondrial DNA mutations have been found to play important roles in carcinogenesis. The most common G10398A mutation, a non-conservative amino acid substitution from Thr to Ala, seems to be involved in the tumorigenesis of breast cancer. Results from studies concerning this mutation remain inconclusive. In the current study, we first took clinical and molecular datasets from case-control studies to determine the association between the G10398A mutation and breast cancer. We further used the Phylotree to determine the haplogroups of this mutation. The frequencies of this mutation in 500 unrelated healthy controls were also screened. We found that this mutation is very common in the human population, and may be a polymorph.

In this study, bioinformatic analysis of gene expression data of head and neck squamous cell carcinoma (HNSCC) was performed to identify critical genes. Gene expression data of HNSCC were downloaded from the Cancer Genome Atlas (TCGA) and differentially expressed genes were determined through significance analysis of microarrays. Protein-protein interaction networks were constructed and used to identify hub genes. Functional enrichment analysis was performed with DAVID. Relevant microRNAs, transcription factors, and small molecule drugs were predicted by the Fisher exact test. Survival analysis was performed with the Kaplan-Meier plot from a package for survival analysis in R. In the five groups of HNSCC patients, a total of 5946 DEGs were identified in group 1, 4575 DEGs in group 2, 5580 DEGs in group 3, 8017 DEGs in group 4, and 5469 DEGs in group 5. DEGs in the cell cycle and immune response were significantly over-represented. Five PPI networks were constructed from which hub genes were acquired, such as minichromosome maintenance complex component 7 (MCM7), MCM2, decorin (DCN), retinoblastoma 1 (RB1), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG). No significant difference in survival was observed among the 5 groups; however, a significant difference existed between two combined groups (groups 1, 3, and 5 vs groups 2 and 4). Our study revealed critical genes in HNSCC, which could supplement the knowledge about the pathogenesis of HNSCC and provide clues for future therapy development.

Previous studies have demonstrated that the CXCL12 G801A polymorphism is closely correlated with tumor susceptibility. In addition, the CXCL12/CXCR4 pathway is closely related to proliferation, metastasis, and invasion of glioma. However, the genetic effects of the CXCL12 G801A polymorphism on glioma risk in Chinese populations remain unknown. In this study, we investigated the potential associations between the CXCL12 G801A polymorphism with glioma susceptibility and its clinicopathological characteristics. Frequencies of CXCL12 G801A polymorphic variants between glioma patients (N = 750) and healthy controls (N = 750) were assessed using restriction length fragment polymorphism analysis. The association among the CXCL12 G801A polymorphism, glioma grade (WHO classification), and histological type was also evaluated. Our results showed that patients with glioma had significantly higher frequency of the CXCL12-3' A/A genotypes (P = 0.039) as compared with healthy controls. When stratified by the glioma histology, high-grade glioma patients had significantly higher frequency of the CXCL12-3' A/A genotypes (P = 0.019) as compared with low-grade glioma patients. When stratified by the WHO grade, significantly higher frequency of the CXCL12-3' A/A genotype was observed in stage IV glioma patients (P = 0.037). We conclude that the CXCL12 G801A polymorphism is a risk factor that increases susceptibility to gliomas in a subset of the general Han Chinese population.

Genetic polymorphisms are defined as changes within the DNA sequences of genes that have frequencies in the population higher than 1%. The glutathione S-transferases play an important role in the cellular detoxification systems involved in oxidative stress that can lead to accumulation of reactive oxygen species. Epidemiological studies have suggested that individuals with homozygous deletion of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) are at higher risk of developing several types of neoplasias. The p53 protein is highly expressed in tumors and transformed cells, and the p53 is a classical tumor suppressor gene involved in regulating cell growth and development. In this study, we investigated the prevalence of polymorphisms in the p53, GSTM1, and GSTT1 genes in a population from Goiânia. We evaluated the polymorphisms of these genes in peripheral blood samples. The null or present polymorphism of GSTM1 and GSTT1 genes and Arg/Pro of the p53 gene were analyzed. Our results revealed a higher frequency of the GSTM1-null polymorphism (72.4%) than the GSTM1-present genotype (27.6%). For GSTT1, we observed higher frequency for the null genotype (65.5%) compared to the present genotype (34.5%). Analysis of p53 gene polymorphisms showed a higher frequency for the genotype Arg/Pro (66%) and a lower frequency for the Arg/Arg (23%) and Pro/Pro (11%) genotypes. It is essential to understand polymorphism frequencies in different populations and to evaluate the role of genetic polymorphisms and their effects on health.

Slug (SNAI2) and Snail (SNAI1) are master regulatory transcription factors for organogenesis and wound healing, and they are involved in the epithelial to mesenchymal transition (EMT) of cancer cells. We found that the activity of phospholipase D isoform 2 (PLD2) is highly increased in cancers with larger size and poor prognosis (MDA-MB-231 versus MCF-7 cells), so we determined if Snail or Slug were responsible for PLD2 gene transcription regulation. Unexpectedly, we found that PLD2 expression was positively regulated by Slug but negatively regulated by Snail. The differential effects are amplified in breast cancer cells over normal cells and with MDA-MB-231 more robustly than MCF-7. Slug putatively binds to the PLD2 promoter and transactivates it, which is negated when Slug and Snail compete with each other. Meanwhile, PLD2 has a negative effect on Snail expression and a positive effect on Slug, thus closing a feedback loop between the lipase and the transcription factors. Further, PA, the product of PLD2 enzymatic reaction, has profound effects on its own and it further regulates the transcription factors. Thus, we show for the first time that the overexpressed PLD2 in human breast tumors is regulated by Slug and Snail transcription factors. The newly uncovered feedback loops in highly invasive cancer cells have important implications in the process of EMT.

To investigate C35 protein expression in breast carcinoma and to investigate its clinicopathological significance, a total of 68 cases of breast carcinoma and 20 cases of normal breast tissue samples were obtained from the clinic. Protein expression of C35, ER, PR and HER-2 were determined using immunohistochemistry. The correlations between C35 expression and clinicopathological parameters were analyzed on the basis of individual clinicopathologic records. Overexpression of C35 was detected in 56 of 68 (82.35%) breast carcinoma samples and only 3 of 20 (15%) normal breast tissue samples, and frequency of C35 expression was significantly associated with clinical Tumor Node Metastasis staging and Scarff-Bloom-Richardson grade (p < 0.05), but was not related to patients age, menstrual status and tumor diameter. C35 expression was positively related with the expression of HER-2 (r = 0.207), whereas negatively related with the expression of ER and PR. Further, C35 was prevalent in all four molecular subtypes of breast carcinoma with no significant difference of expression frequency. However, they have significant differences in lymphatic metastasis cases compared to the non-metastasis cases (p < 0.05). Since C35 protein was extensively expressed in all stages of breast carcinoma, and was closely associated with tumor progression and lymph node metastasis, it might be used as a reliable biomarker or therapeutic target for diagnosis and treatment.