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Introduction Central lymph node status in papillary thyroid microcarcinoma (PTMC) plays an important role in treatment decision-making clinically, however, it is not easy to predict central lymph node metastasis (CLNM). The present work focused on finding the more rational alternative for evaluating central lymph node status while identifying influencing factors to construct a model to predict CLNM incidence. Methods In this study, we retrospectively analyzed the typical sonographic and clinicopathologic features of 546 PTMC patients who underwent surgery, among which, the data of 382 patients were recruited in the training cohort and that of 164 patients in the validation cohort. Based on the outcome of the training cohort, significant influencing factors were further identified through univariate analysis and were considered as independent variables in multivariable logistic regression analysis and incorporated in and presented with a nomogram. Results In total, six independent predictors, including the age, sex, tumor size, multifocality, capsular invasion, Hashimotos thyroiditis were entered into the nomogram. Both internal validation and external validation revealed the favorable discrimination of our as-constructed nomogram. Calibration curves exhibited high consistency. As suggested by decision-curve analyses, the as-constructed nomogram might be applied in clinic. Besides, the model also distinguished patients according to risk stratification. Conclusions The novel nomogram containing remarkable influencing factors for CLNM cases was established in the present work. The nomogram can assist clinicians in clinical decision-making.

BackgroundCircular RNAs (circRNAs) are closely associated with the occurrences and progress of gastric cancer (GC). We aimed to delve into the function and pathological mechanism of Circular RNA-0002570 (circ-0002570) in GC progression.MethodsCircRNAs differentially expressed in GC were screened using bioinformatics technology. The expression of circ-0002570 was detected in GC specimens and cells via qRT-PCR, and the prognostic values of circ-0002570 were determined. The functional roles of circ-0002570 on proliferation, migration, and invasion in GC cells were explored in vitro and in vivo. Interaction of circ-0002570, miR-587, and VCAN was confirmed by dual-luciferase reporter assays, Western blotting, and rescue experiments.ResultsCirc-0002570 expression was distinctly increased in GC tissues compared to adjacent normal specimens, and GC patients with higher circ-0002570 expressions displayed a short survival. Functionally, knockdown of circ-0002570 resulted in the inhibition of cell proliferation, migration, and invasion, and suppressed tumor growth in vivo. Mechanistically, miR-587 was sponged by circ-0002570. VCAN expression in NSCLC was directly inhibited by miR-587. Overexpression of circ-0002570 prevented VCAN from miR-587-mediated degradation and thus facilitated GC progression.ConclusionThe circ-0002570-miR-587-VCAN regulatory pathway promoted the progression of GC. Our findings provided potential new targets for the diagnosis and therapy of GC.

BackgroundPrevious studies have revealed the key functions of N6-methyladenosine (m6A) modification in breast cancer (BC). MALAT1 as a highly m6A modified lncRNA associated with cancer development and metastasis, but the functional relevance of m6A methyltransferase and MALAT1 in BC is still unknown. Here, our study investigated the effects of the novel m6A methyltransferase METTL3 on epithelial-mesenchymal transition (EMT) in BC via the MALAT1/miR-26b/HMGA2 axis.MethodsFirstly, we collected clinical BC samples and cultured BC cells, and detected mRNA and protein levels in the human samples and human cell lines by RT-qPCR and Western blot, respectively. Then, the binding of MALAT1 and miR-26b and the targeting relationship between miR-26b and HMGA2 were examined by dual-luciferase assay. Moreover, the binding of MALAT1 and miR-26b was tested by RNA pull down and RNA immunoprecipitation (RIP) assays. Methylated-RNA immunoprecipitation (Me-RIP) was used to detect the m6A modification level of MALAT1. The interaction of METTL3 and MALAT1 was detected by photoactivatable ribonucleoside-crosslinking immunoprecipitation (PAR-CLIP). Finally, effects on invasion and migration were detected by Transwell.ResultsIn BC, the level of miR-26b was consistently low, while the levels of METTL3, MALAT1 and HMGA2 were high. Further experiments showed that METTL3 up-regulated MALAT1 expression by modulating the m6A modification of MALAT1, and that MALAT1 could promote the expression of HMGA2 by sponging miR-26b. In BC cells, we found that silencing METTL3 could inhibit EMT and tumor cell invasion by suppressing MALAT1. Furthermore, MALAT1 mediated miR-26b to target HMGA2 and promote EMT, migration, and invasion. In summary, METTL3 promoted tumorigenesis of BC via the MALAT1/miR-26b/HMGA2 axis.ConclusionsSilencing METTL3 down-regulate MALAT1 and HMGA2 by sponging miR-26b, and finally inhibit EMT, migration and invasion in BC, providing a theoretical basis for clinical treatment of BC.

Epigenetics is a kind of heritable change that involves the unaltered DNA sequence and can have effects on gene expression. The regulatory mechanism mainly includes DNA methylation, histone modification and non-coding RNA regulation. DNA methylation is currently the most studied aspect of epigenetics. It is widely present in eukaryotic cells and is the most important epigenetic mark in the regulation of gene expression in the cell. DNA methyltransferase inhibitors (DNMTi) have been increasingly recognized in the field of cancer immunotherapy, have been approved for the treatment of acute myeloid leukaemia (AML) and are widely being used in clinical trials of cancer immunotherapies. DNMTi promote the reactivation of tumour suppressor genes, enhance tumour immunogenicity, and stimulate a variety of immune cells to secrete cytokines that exert cytotoxic effects, promote tumour cell death, including macrophages, natural killer (NK) cells and CD8+ T cells, and upregulate major histocompatibility complex (MHC) class I expression levels. Here, we mainly summarize the epigenetics related to DNMTi and their regulation of the antitumour immune response and DNMTi combined with immuno-therapeutics or histone deacetylase inhibitors to demonstrate the great development potential and clinical application value of DNMTi.

Purpose In this study, we investigated the expression and function of Epidermal growth factor receptor kinase substrate 8 (EPS8) in glioblastoma (GBM), and further explored the underlying mechanisms that regulate it. Patients and methods The expression and potential mechanisms of EPS8 in GBM were evaluated through multiple online public databases. The expression level EPS8 in GBM tissues and cell lines were detected by immunohistochemical staining and Western blot. Then, the prognosis of EPS8 and GBM patients were analyzed. Loss-of-function experiments were conducted to determine the role of EPS8 for the biological behavior of GBM cells. In addition, the tumorigenic ability of nude mice was tested in vivo. Results EPS8 is highly expressed in GBM tissues and indicates poor patient prognosis. In cell experiments, EPS8 can promote the proliferation, migration and invasion of GBM cells. In vivo, EPS8 promotes tumor formation in nude mice. EPS8 can activate the PI3K/Akt signaling pathway to function. Conclusion EP8S plays a role in the development of GBM and may be a potential therapeutic target for GBM.

Background Circular RNAs (circRNAs) are closely associated with the occurrences and progress of gastric cancer (GC). We aimed to delve into the function and pathological mechanism of Circular RNA-0002570 (circ-0002570) in GC progression. Methods CircRNAs differentially expressed in GC were screened using bioinformatics technology. The expression of circ-0002570 was detected in GC specimens and cells via qRT-PCR, and the prognostic values of circ-0002570 were determined. The functional roles of circ-0002570 on proliferation, migration, and invasion in GC cells were explored in vitro and in vivo. Interaction of circ-0002570, miR-587, and VCAN was confirmed by dual-luciferase reporter assays, Western blotting, and rescue experiments. Results Circ-0002570 expression was distinctly increased in GC tissues compared to adjacent normal specimens, and GC patients with higher circ-0002570 expressions displayed a short survival. Functionally, knockdown of circ-0002570 resulted in the inhibition of cell proliferation, migration, and invasion, and suppressed tumor growth in vivo. Mechanistically, miR-587 was sponged by circ-0002570. VCAN expression in NSCLC was directly inhibited by miR-587. Overexpression of circ-0002570 prevented VCAN from miR-587-mediated degradation and thus facilitated GC progression. Conclusion The circ-0002570-miR-587-VCAN regulatory pathway promoted the progression of GC. Our findings provided potential new targets for the diagnosis and therapy of GC.

Background: To date, the pathogenesis of gastric cancer (GC) remains unclear. We combined public database resources and bioinformatics analysis methods, explored some novel genes and verified the experiments to further understand the pathogenesis of GC and to provide a promising target for anti-tumor therapy. Methods: We downloaded the chip data related to GC from the Gene Expression Omnibus (GEO) database, extracted differentially expressed genes (DEGs), and then determined the key genes in the development of GC via PPI networks and model analysis. Functional annotation via GO and KEGG enrichment of DEGs was used to understand the latent roles of DEGs. The expression of the triggering receptor expressed on myeloid cells 2 (TREM2) gene in GC cell lines was verified via RT-PCR and western blotting. Moreover, the CCK-8, wound healing assay, and transwell migration and invasion assays were used to understand the changes in the proliferation, migration, and invasion abilities of GC cells after silencing TREM2. Western blotting verified the interaction between TREM2 and PI3K predict of the string website, as well as the effect of TREM2 on EMT. Finally, a lung metastasis model was used to explore the relationship between TREM2 and metastasis. Results: Our study identified 16 key genes, namely BGN, COL1A1, COL4A1, COL5A2, NOX4, SPARC, HEYL, SPP1, TIMP1, CTHRC1, TREM2, SFRP4, FBXO32, GPX3, KIF4A, and MMP9 genes associated with GC. The EMT-related pathway was the most significantly altered pathway. TREM2 expression was higher in GC cell lines and was remarkably associated with tumor invasion depth, TNM stage, histological grade, histological type, anatomic subdivision, and Helicobacter pylori state. Knockdown of TREM2 expression inhibited the proliferation, migration, and invasion of GC cells as well as the progression of EMT by PI3K/AKT signaling in vitro. In addition, lung metastasis were decreased in vivo. Conclusions: We identified some important genes associated with the progression of GC via public database analysis, explored and verified the effects of proto-oncogene TREM2 on EMT via the PI3K/AKT pathway. TREM2 may be a novel target in the GC therapy.

Background Mounting evidence implicates circular RNAs (circRNAs) in various biological processes during cancer progression. Gastric cancer is a main cause of cancer-related deaths worldwide. Herein, we aimed at investigating whether circ_002117 mediates gastric cancer progression through endoplasmic reticulum (ER) stress. Methods Bioinformatics analysis detected differentially expressed circRNAs and their target miRNA candidates, and RT-qPCR was performed to detect expression of circ_002117, microRNA (miRNA)-370 and HERPUD1 in gastric cancer tissues and cells. Gastric cancer cells were transfected with plasmids and their proliferative ability and apoptosis were detected with gain- and loss-of-function assay. The ER of treated cells was observed under a transmission electron microscope. Dual-luciferase reporter gene assay and RIP were performed to detect the interaction between HEPRUD1, miR-370 and circ_002117-treated cells were injected into mice to establish xenograft tumor model. Results Circ_002117 and HEPRUD1 were poorly expressed whereas miR-370 was highly expressed in clinical cancer tissues and cells. Circ_002117 was indicated to target and suppress miR-370 expression, while HERPUD1 was directly targeted by miR-370. Circ_002117 overexpression or miR-370 deficiency promoted ER stress-induced apoptosis and decreased proliferation of gastric cancer cells, which was reversed by silencing of HEPRUD1. Circ_002117 overexpression or miR-370 depletion significantly suppressed gastric cancer tumorigenesis in vivo. Conclusions Taken altogether, circ_002117 facilitated ER stress-induced apoptosis in gastric cancer by upregulating HERPUD1 through miR-370 inhibition.

There is a significant correlation between the degree of tumor differentiation and the survival of patients with gastric cancers. In this report, we compared proteomic differences between poorly differentiated gastric adenocarcinoma tissues and well-differentiated gastric adenocarcinoma tissues in order to identify differentiation-related proteins that may be closely correlated with differentiation of gastric cancer pathogenesis. We identified 7 proteins, of which calreticulin precursor, tapasinERP57 heterodimer, pyruvate kinase isozymes M1/M2 isoform M2, class Pi glutathione S-transferase, and chain A crystal structure of human enolase 1 were upregulated in poorly differentiated gastric adenocarcinoma compared with well-differentiated gastric adenocarcinoma, while myosin-11 isoform SM2A and actin alpha cardiac were downregulated. Two of them, pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 are enzymes involved in glycolytic pathway. The upregulation of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 in poorly differentiated gastric adenocarcinoma was confirmed by Western blotting and immunohistochemistry. Furthermore, we observed 107 cases with gastric adenocarcinoma and found that the high expression of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 correlates with tumor size ( P = .0001 and P = .0017, respectively), depth of invasion ( P = .0024 and P = .0261, respectively), and poor prognosis of patients. In conclusion, with this proteomic analysis, pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 were identified upregulated in poorly differentiated gastric adenocarcinoma comparing with well-differentiated gastric adenocarcinoma. The expression level of pyruvate kinase isozymes M1/M2 isoform M2 and enolase 1 was significantly correlated with overall survival. Some of them would be differentiation-related cancer biomarkers and are associated with tumor metastasis, invasion, and prognosis.

Background Colorectal cancer (CRC) mainly refers to colon and rectum cancer, which is the most common gastrointestinal malignant tumor. MicroRNAs (miRNAs) in tumors participate in multiple processes of malignancy development, including cell differentiation, proliferation, invasion, and metastasis. In this study we explored the relationship of miR-1260b abnormal expression with clinical pathological features in CRC patients. Material/Methods The expression of miR-1260b was detected by real-time quantitative polymerase chain reaction (real-time PCR) in 120 cases of CRC tissues. The correlation of miR-1260b expression with the clinicopathologic features of CRC was analyzed by SPSS 21.0 statistical software. The Kaplan-Meier method was used for survival analysis. Cox regression analyses were conducted to determine whether miR-1260b was an independent predictor of survival for CRC patients. Results The miR-1260b expression in CRC was significantly higher than the expression levels in the corresponding para-carcinoma tissues (P0.05). The high miR-1260b expression patients survived for shorter times than those CRC patients with low miR-1260b expression (P

BACKGROUND MicroRNAs (miRNAs) are responsible for regulating proliferation, differentiation, apoptosis, invasion, and metastasis in tumor cells. miRNA-506 is abnormally expressed in multiple tumors, indicating that it might be oncogenic or tumor-suppressive. However, little is known about the association between miRNA-506 expression and esophageal squamous cell carcinoma (ESCC). MATERIAL AND METHODS We examined the expression of miRNA-506 in the plasma of ESCC patients using quantitative real-time polymerase chain reaction (qRT-PCR) to determine the association between miRNA-506 expression and clinicopathological features of ESCC. ROC curves were produced for ESCC diagnosis by plasma miRNA-506 and the area under curve was calculated to explore its diagnostic value. RESULTS Average miRNA-506 expression levels were remarkably higher in the plasma of ESCC patients than in healthy volunteers (P

BACKGROUND Circulating tumor cells (CTCs) are tumor cells that leave the primary tumor site and enter the bloodstream, where they can spread to other organs; they are very important in the diagnosis, treatment, and prognosis of malignant tumors. However, few studies have investigated CTCs in esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the CTCs in blood of ESCC patients and its potential relevance to clinicopathological features and prognosis. MATERIAL AND METHODS CTCs were acquired by a negative enrichment method that used magnetic activated cell sorting (MACSTM). Fluorescent immunohistochemistry (IHC) was used to identify the CTCs. Then, the positive CTC patients with ESCC were analyzed, after which the relationship between CTCs and clinicopathologic features was evaluated. RESULTS In the present study, 62 out of 140 (44.3%) patients with ESCC were positive for CTCs. The positive rate of CTCs was significantly related with stage of ESCC patients (P=0.013). However, there was no relationship between CTC status and age, sex, smoking tumor history, tumor location, differentiation of tumor, lymphatic invasion, or lymph venous invasion (P>0.05). Kaplan-Meier analysis showed that patients positive for CTCs had significantly shorter survival time than patients negative for CTCs. Multivariate analysis demonstrated that stage and CTC status were significant prognostic factors for patients with ESCC. CONCLUSIONS CTCs positivity is an independent prognostic biomarker that indicates a worse prognosis for patients with ESCC.

This meta-analysis was conducted to quantitatively assess the prognostic significance of p53 expression in gastric cancer patients. A systematic literature search was conducted to identify eligible studies in PubMed and Embase. The pooled hazard ratios (HRs) or odds ratios (ORs) with their corresponding 95 % confidence intervals (95 % CIs) were used to estimate the effect sizes. Moreover, meta-regression analysis and subgroup analysis were carried out. A total of 34 studies comprising 6,599 patients were subjected to final analysis. Positive/high p53 expression was significantly associated with poorer overall survival (HR 1.56, 95 % CI 1.23–1.98) and disease-specific survival (HR 1.52, 95 % CI 1.35–1.73). The results also indicated that positive/high p53 expression was significantly associated with gender (OR 1.26, 95 % CI 1.09–1.45), Lauren’s classification (OR 1.68, 95 % CI 1.23–2.29), the depth of invasion (OR 0.68, 95 % CI 0.56–0.83), lymph node metastasis (OR 1.56, 95 % CI 1.23–1.97), TNM stage (OR 0.57, 95 % CI 0.47–0.69), vascular invasion (OR 1.51, 95 % CI 1.18–1.92) and lymphatic invasion (OR 1.38, 95 % CI 1.11–1.72), but not with Bormann type (OR 1.24, 95 % CI 0.91–1.70), grade of differentiation (OR 1.08, 95 % CI 0.82–1.44) or distant metastasis (OR 1.37, 95 % CI 0.92–2.03). This meta-analysis suggests positive/high p53 expression may be a useful biomarker to predict a poorer prognosis for patients with gastric cancer.

Background The mannose receptor is an immune adhesion molecule mainly expressed on the surface of antigen-presenting cells such as nonmature dendritic cells and macrophages. This study aimed to investigate mannose receptor expression and its predictive role in papillary gastric cancer patients. Methods The expression of the mannose receptor was measured in 120 samples of gastric cancer tissues and corresponding paracarcinoma tissues, by immunohistochemical and quantitative real-time PCR analysis. The relationships between mannose receptor expression and clinicopathological features of gastric cancer patients were analyzed. Results The expression rate of the mannose receptor in gastric cancer cells was 45.8% (54/120), significantly higher than that in the paracarcinoma tissue (20.0%, 36/120) (χ2 = 6.286, p = 0.012). High expression of the mannose receptor was closely related to tumor size, T stage, N stage and Union for International Cancer Control (UICC) stage of gastric cancer (pConclusions High mannose receptor expression indicates poor prognosis for gastric cancer patients. The mannose receptor may be an important molecular marker for gastric cancer prognosis.

The objectives of this review are to compare the effectiveness and safety of radiochemotherapy (RTCT) with radiotherapy (RT) alone in locally advanced cervical cancer (LACC). We comprehensively searched the Cochrane library, Medline, EMBASE, Chinese biomedicine literature database, Chinese scientific full-text database and Chinese journal full-text database for relevant articles. The computer search was supplemented with a manual search of reference lists for all available review articles. Also reference lists of the included studies were reviewed. We included 18 randomized trials involving 3,517 patients. Meta-analysis results are as follows: the response rate, 3 and 5-year survival rates were significantly better in patients in the RTCT group than in RT group. As adverse effects, limited evidence suggests that there was no significant difference between the two groups with regard to rectitis, cystitis, nausea and vomiting. But RTCT group has higher incidence rates than RT group in gastrointestinal, myelosuppression and leucopenia. The combination of radiotherapy and chemotherapy was more effective for LACC than radiotherapy alone. There was no significant difference between the RTCT regimen group and RT regimen group with regard to adverse effects.

α-Enolase is a significant subunit of enolase and acts as a glycolytic enzyme responsible for catalyzing the conversion of 2-phosphoglycerate to phosphoenolpyruvate in the anaerobic glycolysis pathway. The research about their role is known little in tumor invasion and metastasis. This research analyzed the effect of α-enolase in proliferation and progression of human gastric cancer. The constructed PLKO.1-ENO1 shRNA vector was transfected into 293 T cells and used to infect gastric cancer cells, MKN45, by using lentivirus method. Negative controls were generated by infection with viruses containing empty vector PLKO.1-scramble-shRNA by the same protocol and using wild-type MKN45 cells as blank control. The silencing effect was confirmed by reverse transcription polymerase chain reaction and Western blotting at messenger RNA and protein levels, respectively. Cell proliferation and chemosensitivity were tested by methyl-thiazolyl-tetrazolium assay. Cell apoptosis was tested by flow cytometry. The cell line α-enolase short hairpin RNA stabling silence α-enolase was successfully constructed. In the α-enolase short hairpin RNA cell lines, messenger RNA and protein expression of α-enolase were significantly lower than those in negative control and blank control groups. The proliferation and clone formation ability were significantly inhibited, cell apoptosis was increased significantly, and the inhibition rate of chemotherapy drugs was increased ( P < .05). Our data provide strong evidence that α-enolase short hairpin RNA interference vector can effectively suppress the proliferation and increase chemosensitivity of MKN45 cells, which may provide a novel gene therapy for gastric cancer.

Numerous studies examined the association between excision repair complementation group 1 (ERCC1) expression and the prognosis of gastric cancer patients receiving platinum-based chemotherapy but yielded controversial results. We thus conducted a meta-analysis to quantitatively evaluate the prognostic value of ERCC1 expression in gastric cancer patients receiving platinum-based chemotherapy. A systematic literature search was performed to identify relevant studies in PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and WanFang Database up to December 17, 2013. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95 % confidence intervals (CIs) were estimated. Moreover, meta-regression analysis and subgroup analysis were conducted according to ethnicity, HR extraction, detection methods, survival analysis, and quality score. A total of 1,409 patients from 21 studies were subjected to final analysis. Positive/high ERCC1 expression was significantly associated with poorer overall survival (HR, 1.58; 95 % CI, 1.09-2.28), especially in Asians (HR, 1.81; 95 % CI, 1.20-2.73), and lower response rate (OR, 0.26; 95 % CI, 0.18-0.36), but not with clinicopathological features, such as gender (OR, 1.01; 95 % CI, 0.68-1.51), grade (OR, 0.66; 95 % CI, 0.43-1.01), and stage (OR, 1.05; 95 % CI, 0.58-1.90). This meta-analysis suggested that ERCC1 expression might be a useful biomarker to predict response and survival for gastric cancer patients receiving platinum-based chemotherapy, particularly in Asians.

To assess the evidence for improved outcomes in hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE) plus percutaneous ethanol injection (PEI). A systematic search of MEDLINE, EMBASE, the Cochrane library, Chinese biomedicine literature database, Chinese scientific full-text database, and Chinese journal full-text database was undertaken for relevant articles. The computer search was supplemented with a manual search of reference lists for all available review articles, primary studies, and books to identify other studies not found in the computer search. The initial search identified seven randomized trials that included 623 patients. Meta-analysis results are as follows: the 6-month, 1-, 2-, and 3-year survival rates were significantly better in patients with the TACE+PEI group than TACE group; in the decline rates of the AFP level and the reduction rates of tumor size (>50%), the TACE+PEI group has better effects than TACE group; as adverse effects, TACE+PEI group has lower incidence rates than TACE group. In patients with HCC, the efficacy of TACE combined with PEI is significantly better than that of TACE alone. Although there is convincing evidence to confirm the results mentioned, they still need to be confirmed by large sample, multicenter, randomized, controlled trials.