Genetic variants of DNA repair pathway genes on lung cancer risk

As is commonly perceived, polymorphisms in genes of deoxyribonucleic acid (DNA) repair pathway plays a fundamental role in defective DNA repair and mutagenesis prevention and serves to contribute to the individual susceptibility to the development of a variety of cancers. Recently, an increasing number of studies have been dedicated to the contentious and ambiguous links between polymorphisms in genes of DNA repair pathway and lung cancer (LC) risk. In response, a comprehensive updated meta-analysis has been proposed herein to assess the correlation between polymorphisms of DNA repair pathway genes and susceptibility to LC. This paper has identified and retrieved eligible articles from PubMed, Google Scholar, Web of Science, and CNKI databases till February 20, 2019. Finally, 295 case-control studies as to the fourteen polymorphisms of DNA repair pathway genes were enrolled. When the results have been pooled, we have brought to light the conclusion that ERCC2-rs13181 polymorphism has an elevated association with LC risk under allele, heterozygote, and dominant comparisons. In the subgroup analysis by ethnicity, we have found that the Caucasian individuals with “B” variant possess risk of LC which was more than twice as much as allele, homozygote, and recessive models. In comparison, Asian carriers of rs13181 polymorphism in ERCC2 gene are more susceptible to LC in heterozygote, dominant models. To sum up, ERCC2-rs13181 polymorphism could be a critical factor in stimulating LC evolvement. Future studies with a larger sample size and multivariate factors are needed to vindicate these findings.     

Non-coding RNAs: Regulators of glioma cell epithelial-mesenchymal transformation

GBM (glioblastoma multiforme) is the most malignant form of glioma and is the most commonly occurring primary malignant brain tumour. GBM is difficult to completely excise, resulting in an extremely high recurrence rate. The occurrence of an aggressive glioma phenotype depends on EMT (epithelial-mesenchymal transformation), in which epithelial cells transform into mesenchymal cells by losing their cell-cell adhesion and polarity. NcRNAs (non-coding RNAs) play a significant role in the cellular progression from a normal phenotype to a cancerous phenotype. Recently, many studies have shown that there are two essential regulatory ncRNAs, miRNAs (microRNAs) and lncRNAs, which are closely related to EMT. In this review, we conducted a comprehensive investigation of the dysregulated lncRNAs and miRNAs in gliomas with particular attention to the function and regulatory mechanisms of several important lncRNAs and miRNAs, and we discussed their roles as glioma diagnostic and prognostic biomarkers and their potential clinical applications as therapeutic targets.     

NTRK-Fusions – A new kid on the block

The neurotrophic tyrosine receptor kinases (NTRK) play an important role in the development and function of the nervous system. Fusions involving NTRK and a wide range of genes that act as fusion partners are oncogenic and activate well-known signal transduction pathways like the MAPK-ERK pathway. NTRK fusions occur in many very different tumor entities in children and youth as well as in adults. There are a few tumors like secretory breast cancer and congenital fibrosarcoma for which NTRK fusions are pathognomonic. At the same time there a large number of tumors in which NTRK fusions occur in very rare frequency (e.g., lung cancer). TRK inhibitors offer now the possibility to use NTRK fusion as antitumorigenic targets in a tumor agnostic fashion regardless of the basic histology. It is the task of modern pathology to identify such targetable fusions in a highly effective and efficient manner.     

Galectin-3 may serve as a marker for poor prognosis in colorectal cancer: A meta-analysis

Galectin-3 has an important function in the development of tumors. The purpose of this meta-analysis was to explore the relationships between the expression of galectin-3 on clinicopathological features and prognosis of colorectal cancer (CRC). A comprehensive literature search was used to identify eligible studies, and Stata software was conducted using in this meta-analysis. A total of 15 studies, including 1661 cases, were matched in the inclusion criteria. The pooled analysis indicated that galectin-3 expression was related to the poor overall survival (OS) in CRC patients (HR: 1.77, 95% CI: 1.36–2.31, P < 0.0001). Our meta-analysis also showed that cancerous tissues have higher levels of galectin-3 expression than normal tissues. Besides, positive galectin-3 expression was also related to advanced TNM stages(III/IV vs. I/II: OR 5.30, 95% CI: 2.42–11.61, P < 0.0001), higher Duke’s stages (C/D vs. A/B: OR 4.00, 95% CI: 2.22–7.22, P < 0.0001), venous invasion (venous invasion vs. not: OR 3.02, 95%CI: 1.75–5.22, P < 0.0001) and higher CEA level (CEA≥5 ng/ml vs. ≤ 5 ng/ml: OR 2.09, 95% CI: 1.09–4.03, P = 0.03). In summary, our results indicated that overexpression of galectin-3 is significantly related to the tumor progression and could be a efficient in predicting the prognosis of patients with CRC.     

Clinicopathological and prognostic significance of TINCR in caner: A meta-analysis

BackgroundIn a variety of cancers, the expression of TINCR is linked to the development, progression, metastasis, invasion, and prognosis of cancer. Our study is the first study used meta-analysis to explore the relationship between TINCR expression and cancer.MethodsBy looking up PubMed, Web of Science, CNKI database, we obtained 10 articles for analysis. The statistical analysis was all calculated by Stata 15.1 software.ResultsWe found that the expression of TINCR was a risk factor to the size of the tumor (OR = 1.772, 95%CI: 1.246–2.520, P = 0.001). In univariate analysis, patients with high expression of TINCR had poor OS (pooled HR = 1.533, 95%CI: 1.025–2.294, P = 0.038). Similar result was also found in multivariate analysis In subgroup analysis (pooled HR = 1.610, 95%CI: 1.356–1.913, P = 0.000).We also found that over-expression of TINCR had poor OS in breast cancer (pooled HR = 1.582, 95%CI: 1.126–2.223, P = 0.008).ConclusionIn this study, we found that over-expression of TINCR may influence the tumor size and contribute to the poor prognosis of cancer.     

Expression and prognostic value of FOXP1 in esophageal squamous cell carcinoma

BackgroundForkhead box protein P1 (FOXP1) has been suggested as a prognostic marker in several malignant tumors. However, the significance of FOXP1 in esophageal squamous cell carcinoma (ESCC) is still unclear. The purpose of this study was to investigate the expression pattern of FOXP1 in normal esophageal tissue and ESCC and to analyze the clinicopathological significance and prognostic value of FOXP1 in ESCC.MethodsFOXP1 was detected by immunohistochemistry using tissue microarrays containing tumor tissues and adjacent normal tissues from 270 ESCC patients with oncological follow-up data.ResultsNormal esophageal tissues predominantly showed an exclusive nuclear FOXP1 (n-FOXP1) expression pattern, and no exclusive cytoplasmic FOXP1 (c-FOXP1) staining was found. In ESCC, the expression rates of exclusive n-FOXP1-positive, exclusive c-FOXP1-positive, both nuclear and cytoplasmic positive and complete negative were 14.4%, 28.9%, 10.4% and 46.3%, respectively. High n-FOXP1 expression was significantly correlated with decreased postoperative recurrence and distant metastasis (P < 0.05). Furthermore, elevated c-FOXP1 expression was significantly associated with regional lymph node metastasis and distant metastasis (P < 0.05). High c-FOXP1 expression had an effect on shorter overall survival (OS) time, but the difference was not statistically significant (P > 0.05). Kaplan–Meier analysis showed that ESCC patients with high n-FOXP1 expression survived significantly longer than patients with low n-FOXP1 expression. Multivariate analysis confirmed that patients with high n-FOXP1 staining exhibit good prognosis and n-FOXP1 was an independent factor for ESCC prognosis.ConclusionsOur results suggest that FOXP1 plays an essential role in ESCC progression and prognosis and may be a useful biomarker for predicting survival.     

MicroRNA-301b-3p accelerates the growth of gastric cancer cells by targeting zinc finger and BTB domain containing 4

MicroRNAs (miRNAs) have been found to be aberrantly expressed and exert essential roles in the tumorigenesis and progression of gastric cancer (GC). miR-301b-3p has been recognized as a cancer-related miRNA in lung cancer, bladder cancer and hepatocellular carcinoma. However, the function of miR-301b-3p in GC progression and its underlying mechanism have not been studied yet. In this study, we found that miR-301b-3p expression was up-regulated in GC tissues compared to adjacent noncancerous tissues. Furthermore, the elevated levels of miR-301b-3p were detected in GC cell lines (SGC-7901, AGS, MKN-45 and MGC-803) as compared with GES-1 cells. Interestingly, GC tissues from patients with tumor size ≥ 5 cm and advanced tumor stages showed obvious higher levels of miR-301b-3p compared to matched controls. Functionally, miR-301b-3p knockdown prominently inhibited cell proliferation, and induced cell cycle arrest at G1 phase and apoptosis in MGC-803 cells. Meanwhile, ectopic expression of miR-301b-3p conversely regulated these biological behaviors of MKN-45 cells. Next, we found that miR-301b-3p knockdown increased, whereas miR-301b-3p overexpression reduced the expression of zinc finger and BTB domain containing 4 (ZBTB4) in GC cells. Accordingly, luciferase reporter assay identified ZBTB4 as a direct target of miR-301b-3p. ZBTB4 overexpression markedly restrained the growth of MGC-803 cells. More importantly, ZBTB4 silencing partially reversed miR-301b-3p knockdown-induced tumor suppressive effects on MGC-803 cells. In conclusion, we firstly revealed that miR-301-3p was highly expressed in GC and contributed to tumor progression via attenuating ZBTB4, which might provide a novel molecular-targeted strategy for GC treatment.     

Expression of co-inhibitory molecules B7-H4 and B7-H1 in Epstein-Barr virus positive diffuse large B-cell lymphoma and their roles in tumor invasion

To investigate the relationship between immunoregulatory molecules B7-H4 and B7-H1 in Epstein-Barr positive diffuse large B-cell lymphoma (EBV⁺DLBCL). Immunohistochemistry was used to detect the expression of B7-H4 and B7-H1 in tumor tissues of 13 patients with EBV⁺DLBCL. The expression levels of B7-H4 and B7-H1 in four diffuse large B-cell lymphoma cell lines (SU-DHL-4, SU-DHL-10, SU-DHL-6, Pfeiffer) were analyzed by flow cytometry. Transwell invasion assays were conducted to observe the invasive ability of cell lines. B7-H4 and B7-H1 were expressed in 84.62% and 100% tumor specimens of EBV⁺DLBCL. The overexpression of B7-H4 and B7-H1 was found in 46.15% and 23.08% tumor samples of EBV⁺DLBCL. There was a medium negative correlation between the expression levels of B7-H4 and B7-H1 (r = -0.667, P = 0.013, spearman rank correlation). The expression levels of B7-H1 in four diffuse large B-cell lymphoma cell lines were positively correlated with their invasive ability, whereas the expression levels of B7-H4 were not. Here, we provide evidence for the negative relationship between B7-H4 and B7-H1 in EBV⁺DLBCL. The expression of B7-H1 in EBV⁺DLBCL appears to be the dominant factor which affects tumor aggressiveness. When B7-H1 expression weakens, the molecule B7-H4 may become the dominant factor of prognosis in patients with EBV⁺DLBCL.