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Chengwen Zhao,1,* Yonghui Liu,1,* Shaoqing Ju,1,2 Xudong Wang1,2 1Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu, People’s Republic of China; 2Department of Public Health, Nantong University, Nantong, Jiangsu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xudong WangDepartment of Laboratory Medicine, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, Jiangsu, 226006, People’s Republic of ChinaTel +86 13951318000Email wangxudong88@hotmail.comBackground: Fat mass and obesity-associated protein (FTO) is a critical N6-methyladenosine (m6A) demethylase that participates in tumorigenesis and is associated with the prognosis of patients in some cancers. However, the key roles of FTO in pan-cancer are still largely obscure.Methods: FTO expression levels in pan-cancer were estimated via the Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), and The Cancer Genome Atlas (TCGA) databases. Univariate survival analysis was used to estimate the effects of FTO on prognosis. In addition, we used the Tumor Immune Evaluation Resource (TIMER) to assess the immune cell infiltration of FTO gene across cancers. The association of FTO expression with immune checkpoint genes expression, DNA mismatch repair (MMR) gene mutation, DNA methyltransferases, microsatellite instability (MSI), and tumor mutational burden (TMB) was investigated using Spearman’s correlation analysis. Moreover, Gene Set Enrichment Analysis (GSEA) was utilized to identify critical pathways in cancers. The STRING website was used to reveal the protein–protein interaction (PPI) network of FTO.Results: FTO was aberrantly expressed across cancers and survival analysis demonstrated that its expression was associated with clinical prognosis of many cancer patients. Specifically, FTO expression was significantly associated with immune infiltrating cells in colon adenocarcinoma, kidney renal clear cell carcinoma, and liver hepatocellular carcinoma. In addition, FTO expression was significantly associated with immune checkpoint genes expression, MMR, DNA methyltransferases levels, TMB, and MSI in multiple cancers. Moreover, the GSEA unveiled that FTO was involved in the regulation of tumors and immune-related signaling pathways. In addition, several m6A related genes were implicated in the PPI network of FTO.Conclusion: FTO was related to patients’ prognosis and tumor immune infiltrates in various cancers, and may serve as a novel and potential prognostic and immune biomarker in human pan-cancer.Keywords: FTO, biomarker, prognosis, tumor immune, pan-cancer

Background Homocysteine (Hcy) is considered to be a risk factor for cardiovascular and cerebrovascular diseases. Few studies have evaluated the distribution of Hcy on a large-scale health examination. Accordingly, this study aimed to investigate the level and distribution of Hcy in the population with healthy physical examination and the correlation with other biomarkers, and analyzed for cardiovascular and other diseases. Methods Measurements of serum Hcy, TC, TG, LDL-c, HDL-c, ALT, ALP, γ-GT, TBIL, GLU, urea, Cr, UA, and related metabolic risk factors were selected for analysis from 8063 medical examination samples collected from February 2017 to April 2020. The relationship between Hcy and other biochemical indicators were evaluated with the multivariate regression model of age, gender, smoking, drinking, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Results Among 8063 cases, the age, BMI, SBP, and DBP of the high-Hcy group were higher than those of the low-Hcy group, the difference was statistically significant (P P P = 0.002) and the Hcy of abnormal TG and HDL is higher than that of the normal blood lipid group (P P P = 0.007). In multivariate analysis, lnHDL-C was negatively correlated with lnHcy (β = − 0.038, SE = 0.016, P = 0.019), lnCr was positively correlated with lnHcy (β = 0.055, SE = 0.016, P P = 0.022). Conclusion Hcy is closely related to HDL-c, Cr, and UA, which indicates that Hcy may affect the metabolism of HDL-c and UA, and can also be used as an auxiliary diagnostic index for kidney injury.

The purpose of this study was to determine whether circular RNA hsa_circ_0002874 could serve as a novel biomarker for the diagnosis of gastric cancer (GC). The expression level of hsa_circ_0002874 mean (interquartile range [IQR]) in the plasma of patients with GC, patients with benign gastric lesions, and healthy individuals was 3.482 (IQR, 1.524–9.048), 1.261 (IQR, 0.817–2.000), and 1.00 (IQR, 0.726–1.382), respectively, whereas there was no significant difference between the latter 2 groups. The plasma expression level of hsa_circ_0002874 was significantly correlated with tumor stage (U = 234.0; P

Gastric cancer (GC) is one of the common malignant tumors with high mortality. The abundance of miRNAs in serum exosomes has proved to have a high application value as a new noninvasive diagnostic method. The purpose of this study was to investigate whether serum exosomal miR-92a-3p could be used as a new biomarker for early diagnosis of GC and evaluate its clinical application value by detecting the expression of serum exosomal miR-92a-3p in 131 patients with primary GC and 122 healthy controls by real-time quantitative (qRT)-PCR. The results showed that the expression level of serum exosomal miR-92a-3p in GC patients was significantly lower than that in normal controls (p < 0.0001). In addition, the level was closely correlated with lymph node metastasis and tumor node metastasis stage of GC patients. The area under the curve for serum exosomal miR-92a-3p was 0.829, significantly higher than for other indicators. Furthermore, combined detection of serum exosomal miR-92a-3p, CEA and CA19-9 was more sensitive than any of the three alone or any pair. These results showed that serum exosomal miR-92a-3p could be used as a novel new tumor biomarker to improve diagnostic efficiency in GC.

Colorectal cancer (CRC) is the second most incident cancer and third leading cause of cancer-related mortality worldwide. Small nucleolar RNAs (snoRNAs) are small non-coding RNAs located in the nucleoli of cells, and play key roles in multiple cancers. However, the role of serum snoRNAs in CRC remains unknown. We analyzed the expression of the snoRNA SNORD1C in the serum of patients with CRC using quantitative real-time polymerase chain reaction (qRT-PCR) (n = 122). The receiver operating characteristic (ROC) curves were estimated, and the area under the ROC curve (AUC) was calculated. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis of co-expressed genes was performed using the database for annotation, visualization, and integrated discovery (DAVID), and visualized by R language. The results showed that the expression of SNORD1C in patients with CRC (n = 122) was significantly higher than that in normal individuals (n = 50) and patients with benign colorectal disease (n = 33) (P < 0.05). The overexpression of serum SNORD1C was related to poor tissue differentiation and high carcinoembryonic antigen (CEA) levels (P < 0.05). In the ROC curve analysis, SNORD1C serum expression combined with CEA offered better predictive value for the diagnosis of CRC (AUC = 0.838) compared with SNORD1C (AUC = 0.748) or CEA (AUC = 0.715) alone. High expression of SNORD1C was found to be closely associated with prognosis and unfavorable outcomes in patient with CRC. Therefore, serum SNORD1C may be a noninvasive tumor biomarker for diagnosis of CRC.

BACKGROUND: Long intergenic non-coding RNA (lincRNA) belongs to a special type of RNA that is unable to encode proteins but has been proved to play a role in gene regulation and differentially expressed in various malignant tumors. OBJECTIVE: In this study, we aimed to identify whether lincRNA LINC00173 was differentially expressed in non-small-cell lung cancer (NSCLC) and whether it could serve as a potential diagnostic biomarker. METHODS: The quantification real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of LINC00173 in serum and cultured cells. For large sample analysis, the lncRNA expression matrix in TCGA database were generated via R software. To evaluate the diagnostic performance of serum LINC00173, the receiver operating characteristic (ROC) curve was used. RESULTS: The qRT-PCR analysis showed that the serum LINC00173 expression level in 108 NSCLC patients was higher than that in 91 healthy donors and 55 patients with benign pulmonary disease (BPD). And the area under the curve (AUC) of serum LINC00173 was 0.809 for the diagnosis of NSCLC (95% CI: 0.750–0.868, p< 0.001), 0.670 for BPD (95% CI: 0.584–0.756, P< 0.001), and 0.730 for small-cell lung cancer (SCLC, 95% CI: 0.636–0.825, P< 0.001). Besides, we established a diagnostic model of combined detection of LINC00173, CEA and Cyfra21-1, and found that combined detection of these indicators significantly improved the diagnostic efficiency. Analysis of the Clinicopathological parameters showed that high LINC00173 expression was correlated with histological typing of tumor, tumor metastasis and serum Cyfra21-1 levels. In addition, serum LINC00173 expression decreased in patients who received chemotherapy and rebound in recurrent NSCLC patients. CONCLUSION: Serum LINC00173 may prove to be a potential non-invasive auxiliary diagnostic biomarker for NSCLC patients.

Purpose Due to the lack of specific and sensitive detection indicators, most patients with GC are already in the advanced stage at the time of diagnosis. Therefore, it is urgent to search for effective diagnostic biomarkers that can be applied in clinic. Materials and Methods We screened out circ_0004771 through circRNA sequencing. Exonuclease digestion assay, agarose gel electrophoresis (AGE) and Sanger sequencing verified the potential of circ_0004771 being a biomarker. Additionally, we established quantitative real-time fluorescent polymerase chain reaction (qRT-PCR) to detect the expression level of circ_0004771 and evaluated the methodology. What's more, we collected plasma samples from 120 GC patients, 40 superficial gastritis patients, 20 postoperative GC patients, 20 postoperative recurrence patients and 120 healthy donors. We constructed the receiver operating characteristic curve (ROC) to appraise its diagnostic efficacy. Results The expression level of circ_0004771 is up-regulated in GC tissues, which is consistent with circRNA sequencing result (P=0.0001). Circ_0004771 can serve as a promising biomarker because of its stable structure and longer half-life. Plasma circ_0004771 expression is markedly richer in GC patients than that in normal people (P

Aim: Long noncoding RNA (lncRNA) B3GALT5-AS1 has been reported as a biomarker for cancer monitoring. This research aims to identify serum long noncoding RNA B3GALT5-AS1 as a new biomarker for the diagnosis of colorectal cancer (CRC) and evaluate its clinical value. Materials & methods: Serum B3GALT5-AS1 expression levels were measured by quantitative real-time PCR. Results: The level of B3GALT5-AS1 in CRC patients was significantly lower than that of healthy patients (p < 0.0001). Further exploration validated that high serum B3GALT5-AS1 level was related to tumor node metastasis (TNM) stage (p = 0.008) and histological differentiation (p = 0.027). Compared with the healthy control group, AUCROC of serum B3GALT5-AS1 in the CRC group was 0.762 with 95% CI: 0.698–0.826 (p < 0.0001). Conclusion: B3GALT5-AS1 may be served as a diagnostic marker for distinguishing CRC patients from healthy people.

Background: Colorectal cancer (CRC) is a leading cause of cancer death, and early diagnosis of CRC could significantly reduce its mortality rate. Previous studies suggest that the DNA methylation status of zinc finger genes (ZFGs) could be of potential in CRC early diagnosis. However, the comprehensive evaluation of ZFGs in CRC is still lacking.Methods: We first collected 1,426 public samples on genome-wide DNA methylation, including 1,104 cases of CRC tumors, 54 adenomas, and 268 para-tumors. Next, the most differentially methylated ZFGs were identified and validated in two replication cohorts comprising 218 CRC patients. Finally, we compared the prediction capabilities between the ZFGs and the SEPT9 in all CRC patients and the KRAS + and KRAS- subgroup.Results: Five candidate ZFGs were selected: ESR1, ZNF132, ZNF229, ZNF542, and ZNF677. In particular, ESR1 [area under the curve (AUC) = 0.91] and ZNF132 (AUC = 0.93) showed equivalent or better diagnostic capability for CRC than SEPT9 (AUC = 0.91) in the validation dataset, suggesting that these two ZFGs might be of potential for CRC diagnosis in the future. Furthermore, we performed subgroup analysis and found a significantly higher diagnostic capability in KRAS + (AUC ranged from 0.97 to 1) than that in KRAS- patients (AUC ranged from 0.74 to 0.86) for all these five ZFGs, suggesting that these ZFGs could be ideal diagnostic markers for KRAS mutated CRC patients.Conclusion: The methylation profiles of the candidate ZFGs could be potential biomarkers for the early diagnosis of CRC, especially for patients carrying KRAS mutations.

Colorectal cancer (CRC) is a common malignancy that has both low 5-year survival and high prevalence. Immunotherapy has achieved impressive progress for treatment of CRC, but still faces huge challenges. Although large tumor suppressor 2 (LATS2) is well accepted to be related to cancer progression, the prognostic potential and immune response role of LATS2 expression in CRC remain unclear. To investigate the value of LATS2 for prognosis and immune infiltration, a retrospective study of 213 CRC patients was carried out. We determined the expression of LATS2 in tumor tissues by immunohistochemistry. The results indicated that LATS2 expression was down-regulated in CRC tissues and clearly related to tumor differentiation (P = 0.002) and TNM stage (P = 0.002). Low LATS2 expression and TNM stage were subsequently identified as significant independent predictors of prognosis in CRC by univariate and multivariate analyses. In Kaplan–Meier survival analyses, CRC patients with elevated LATS2 expression and early TNM stage had better overall survival. We further found that LATS2 was involved in the regulation of immune-related pathways and that its expression was positively related to tumor-infiltrating immune cells by GSEA, TIMER, and ssGSEA analyses. In summary, our data imply that LATS2 may act as a cancer suppressor gene and be correlated with clinical prognosis and immune infiltration in CRC. Thus, LATS2 may be applied as a novel biomarker for predicting clinical outcomes and immune infiltration levels in CRC.

Gastric cancer (GC) is considered one of the most common gastrointestinal malignancies worldwide. Circular RNAs (circRNAs) are a new class of endogenous noncoding RNAs, which can be used as biomarkers and therapeutic targets for many tumors. However, the role and potential regulatory mechanisms of circRNAs in GC remain unclear. In this study, we demonstrated that a specific circRNA, circHAS2, was upregulated in GC tissues and cells and was positively correlated with tumor metastasis. In vitro experiments demonstrated that circHAS2 knockdown or the addition of hsa-miR-944 mimics inhibited the proliferation, migration, and invasion ability of GC cells and affected the epithelial-mesenchymal transition. In addition, hsa-miR-944 interacted with protein phosphatase, Mg2+/Mn2+-dependent 1E (PPM1E), and was found to be a target gene of circHAS2. The upregulation of PPM1E reversed the effects of circHAS2 knockout on GC cells. The circHAS2/hsa-miR-944/PPM1E axis may be involved in the progression of GC; thus, circHAS2 may be a potential biomarker and therapeutic target for GC.

Despite significant progress in the treatment of myeloma, multiple myeloma (MM) remains an incurable hematological malignancy due to cell adhesion-mediated drug resistance (CAM-DR) phenotype. However, data on the molecular mechanisms underlying the CAM-DR remains scanty. Here, we identified a miRNA-mRNA regulatory network in myeloma cells that are directly adherent to bone marrow stromal cells (BMSCs). Our data showed that the BMSCs up-regulated miR-30a-5p and down-regulated BCL2L11 at both mRNA and protein level in the myeloma cells. Besides, luciferase reporter genes demonstrated direct interaction between miR-30a-5p and BCL2L11 gene. Moreover, the BMSCs activated NF-ΚB signaling pathway in myeloma cells and the NF-κB P65 was shown to directly bind the miR-30a-5p promoter region. Moreover, suppression of the miR-30a-5p or upregulation of the BCL2L11 promoted apoptosis of the myeloma cells independent of the BMSCs, thus suggesting clinical significance of miR-30a-5p inhibitor and PLBCL2L11 plasmid in CAM-DR. Together, our data demonstrated the role of P65-miR-30a-5p-BCL2L11 loop in CAM-DR myeloma cells. These findings give new insights into the role of tumor microenvironment in the treatment of patients with myeloma.

Objective: Multiple myeloma (MM) as a hematological malignancy remains mostly incurable at present. The aim of the current study was to investigate the potential of serum microRNA (miRNA) as a novel biomarker for MM.Methods: This study recruited 90 MM patients and 30 healthy controls. Bone marrow samples were obtained from 12 MM patients and 6 healthy controls. The expression level of miR-148a/152 was determined by qRT-PCR. The diagnostic performance and prognostic prediction of miR-148a/152 expression were analyzed by ROC curve and Kaplan-Meier method respectively. Serum IgA, IgG, κ light chain, λ light chain and β2 microglobulin levels were detected by immunoturbidimetry. Serum LDH level was detected by lactic acid substrate method.Results: The expression levels of miR-148a and miR-152 were elevated in serum and CD138+ plasma cells of MM patients as compared with controls (PConclusion: The results of the present study suggest that circulating miR-148a and miR-152 may prove to be a marker for diagnosis and prognostic prediction of MM.

BackgroundGastric cancer (GC) is one of the malignant tumors with the highest morbidity and mortality in the world. Early diagnosis combined with surgical treatment can significantly improve the prognosis of patients. Therefore, it is urgent to seek higher sensitivity and specificity biomarkers in GC. tRNA-derived small RNAs are a new non-coding small RNA that widely exists in tumor cells and body fluids. In this study, we explore the expression and biological significance of tRNA-derived small RNAs in GC.Materials and MethodsFirst of all, we screened the differentially expressed tRNA-derived small RNAs in tumor tissues by high-throughput sequencing. Agarose gel electrophoresis (AGE), Sanger sequencing, and Nuclear and Cytoplasmic RNA Separation Assay were used to screen tRF-31-U5YKFN8DYDZDD as a potential tumor biomarker for the diagnosis of GC. Then, we detected the different expressions of tRF-31-U5YKFN8DYDZDD in 24 pairs of GC and paracancerous tissues, the serum of 111 GC patients at first diagnosis, 89 normal subjects, 48 superficial gastritis patients, and 28 postoperative GC patients by quantitative real-time PCR (qRT-PCR). Finally, we used the receiver operating characteristic (ROC) curve to analyze its diagnostic efficacy.ResultsThe expression of tRF-31-U5YKFN8DYDZDD has good stability and easy detection. tRF-31-U5YKFN8DYDZDD was highly expressed in tumor tissue, serum, and cell lines of GC, and the expression was significantly related to TNM stage, depth of tumor invasion, lymph node metastasis, and vascular invasion. The expression of serum tRF-31-U5YKFN8DYDZDD in the GC patients decreased after the operation (P = 0.0003). Combined with ROC curve analysis, tRF-31-U5YKFN8DYDZDD has better detection efficiency than conventional markers.ConclusionsThe expressions of tRF-31-U5YKFN8DYDZDD in the tumor and paracancerous tissues, the serum of GC patients and healthy people, and the serum of GC patients before and after operation were different. tRF-31-U5YKFN8DYDZDD is not only a diagnostic biomarker of GC but also a predictor of poor prognosis.

Despite the continuous improvement of various therapeutic techniques, the overall prognosis of tumors has been significantly improved, but malignant tumors in the middle and advanced stages still cannot be completely cured. It is now evident that cell adhesion-mediated resistance (CAM-DR) limits the success of cancer therapies and is a great obstacle to overcome in the clinic. The interactions between tumor cells and extracellular matrix (ECM) molecules or adjacent cells may play a significant role in initiating the intracellular signaling pathways that are associated with cell proliferation, survival upon binding to their ligands. Recent studies illustrate that these adhesion-related factors may contribute to the survival of cancer cells after chemotherapeutic therapy, advantageous to resistant cells to proliferate and develop multiple mechanisms of drug resistance. In this review, we focus on the molecular basis of these interactions and the main signal transduction pathways that are involved in the enhancement of the cancer cells’ survival. Furthermore, therapies targeting interactions between cancer cells and their environment to enhance drug response or prevent the emergence of drug resistance will also be discussed.

BackgroundIt has been reported that long non-coding RNAs (lncRNAs) can be regarded as a biomarker and had particular clinical significance for early screening and gastric cancer (GC) diagnosis. Therefore, this study aimed to investigate whether serum HCP5 could be a new diagnostic biomarker.MethodsFiltered out the HCP5 from the GEO database. The specificity of HCP5 was verified by real-time fluorescence quantitative PCR (qRT-PCR), and then the stability of HCP5 was verified by room temperature storage and repeated freeze-thaw experiments. Meanwhile, the accuracy of HCP5 was verified by agarose gel electrophoresis (AGE) and Sanger sequencing. Simultaneously, the expression level of serum HCP5 was detected by qRT-PCR in 98 patients with primary gastric cancer, 21 gastritis patients, 82 healthy donors, and multiple cancer types. Then, the methodology analysis was carried on. Moreover, receiver operating characteristic (ROC) was used to evaluate its diagnostic efficiency.ResultsqRT-PCR method had good repeatability and stability in detecting HCP5. The expression level of HCP5 in the serum of gastric cancer patients was remarkably higher than that of healthy controls, and it could distinguish gastritis patients from healthy donors. Besides, the expression of HCP5 was increased dramatically in MKN-45 and MGC-803. The FISH assay showed that HCP5 was mainly distributed in the cytoplasm of MKN-45 and BGC-823 cells. When HCP5 was combined with existing tumor markers, the diagnostic efficiency of HCP5 was the best, and the combined diagnosis of carcinoembryonic antigen (CEA), carbohydrate antigen199 (CA199), and HCP5 can significantly improve the diagnostic sensitivity. Besides, compared with the expression levels of thyroid cancer (THCA), colorectal cancer (CRC), and breast cancer (BRCA), serum HCP5 in gastric cancer was the most specific. Moreover, the high expression of serum HCP5 was related to differentiation, lymph node metastasis, and nerve invasion. The term of serum HCP5 after the operation was significantly lower than that of patients with primary gastric cancer.ConclusionSerum HCP5 can be used as a potential biomarker of non-invasive fluid biopsy, which had a unique value in the early diagnosis, development, and prognosis of gastric cancer.

Background: Homocysteine (Hcy) is considered to be an independent risk factor for cardiovascular and cerebrovascular diseases. No study has evaluated the distribution of Hcy on a large-scale health examination. Accordingly, this study aimed to investigate the level and distribution of Hcy in the healthy physical examination population and the correlation with other biomarkers, and analyzed for cardiovascular and other diseases. The prevention provides an important scientific basis.Methods: From February 2017 to April 2020, 8063 medical examination populations were selected for analysis. Determination of serum Hcy, TC, TG, LDL-c, HDL-c, ALT, ALP, γ-GT, TBIL, GLU, urea, Cr, UA and related metabolic risk factors. According to the multivariate regression model of age, gender, smoking, drinking, body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP), the relationship between Hcy and other biochemical indicators was evaluated. Results: Among 8063 cases, the age, BMI, SBP and DBP of the high-Hcy group were higher than those of the low-Hcy group, the difference was statistically significant (PPPPP>0.05). In multivariate analysis, lnHDL-C was negatively correlated with lnHcy (β=-0.038, SE=0.016, PPP Conclusion: Hcy is closely related to HDL-c, Cr and UA, which indicates that Hcy may affect the metabolism of HDL-c and UA, and can also be used as an auxiliary diagnostic index for kidney injury.

BackgroundGastric cancer (GC) is one of the most common malignant tumors globally and the third leading cause of cancer-related death. Currently, the sensitivity and specificity of diagnostic markers for GC are low, so it is urgent to find new biomarkers with higher sensitivity and specificity. tRNA-derived small RNAs are a kind of small non-coding RNAs derived from tRNAs. It is abundant in cancer cells and body fluids. Our goal is to find the differentially expressed tRNA-derived small RNAs in GC to explore their potential as a GC biomarker.MethodsQuantitative real-time PCR was used to detect the expression level of hsa_tsr016141. The molecular characteristics of hsa_tsr016141 were verified by agarose gel electrophoresis, Sanger sequencing, Actinomycin D Assay, and Nuclear and Cytoplasmic RNA Separation Assay. The diagnostic efficiency of hsa_tsr016141 was analyzed through receiver operating characteristic.ResultsThe expression level of hsa_tsr016141 in GC tissues and serum was significantly increased. The serum expression level showed a gradient change between GC patients, gastritis patients, and healthy donors and was positively correlated with the degree of lymph node metastasis and tumor grade. ROC analysis showed that the serum expression level of hsa_tsr016141 could significantly distinguish GC patients from healthy donors or gastritis patients. Besides, the expression level of hsa_tsr016141 in GC patients decreased significantly after the operation (PConclusionsSerum hsa_tsr016141 has good stability and specificity and can be used for dynamic monitoring of GC patients, suggesting that serum hsa_tsr016141 can be a novel biomarker for GC diagnosis and postoperative monitoring.

Background Aberrant DNA methylation has been firmly established as a factor contributing to the pathogenesis of colorectal cancer (CRC) via its capacity to silence tumour suppressor genes. However, the methylation status of multiple tumour suppressor genes and their roles in promoting CRC metastasis are not well characterised. Methods We explored the methylation and expression profiles of CPEB1 (the gene encoding cytoplasmic polyadenylation element-binding protein 1), a candidate CRC tumour suppressor gene, using The Cancer Genome Atlas (TCGA) database and validated these results in both CRC cell lines and cells from Han Chinese CRC patients (n = 104). The functional role of CPEB1 in CRC was examined in experiments performed in vitro and in vivo. A candidate transcription factor capable of regulating CPEB1 expression was predicted in silico and validated by luciferase reporter, DNA pull-down, and electrophoretic mobility shift assays. Results Hypermethylation and decreased expression of CPEB1 in CRC tumour tissues were revealed by TCGA database. We also identified a significant inverse correlation (Pearson’s R = − 0.43, P CPEB1 expression. We validated these results in CRC samples and two CRC cell lines. We also demonstrated that up-regulation of CPEB1 resulted in significantly decreased tumour growth, migration, invasion, and tumorigenicity and promoted tumour cell apoptosis both in vitro and in vivo. We identified the transcription factors CCAAT enhancer-binding protein beta (CEBPB) and transcription factor CP2 (TFCP2) as critical regulators of CPEB1 expression. Hypermethylation of the CPEB1 promoter resulted in a simultaneous increase in the capacity for TFCP2 binding and a decreased likelihood of CEBPB binding, both of which led to diminished expression of CPEB1. Conclusions Our results identified a novel tumour-suppressive role of CPEB1 in CRC and found that hypermethylation of the CPEB1 promoter may lead to diminished expression due to decreased chromatin accessibility and transcription factor binding. Collectively, these results suggest a potential role for CPEB1 in the diagnosis and treatment of CRC.

Regulated in development and DNA damage responses 1 (REDD1) is a highly conserved stress-response protein and can be induced by hypoxia/ischemia and DNA damage. However, it is not known whether REDD1 involves in neuronal damage caused by subarachnoid hemorrhage (SAH) that is known as one of the most important causes of disability and death worldwide. Here, we first found that SAH markedly induced the increase of REDD1 (35.467 ng/ml) in cerebrospinal fluid (CSF) of patients at acute stage (within 24 h from bleeding) compared to that of control (0.644 ng/ml). And, REDD1 level was positively correlated with severity of brain injuries (Hunt-Hess grade of SAH), but it showed an obvious decline at recovery stage 6.201 ng/ml (before discharge from hospital) because of good recovery. Moreover, it was found that the expression of REDD1 was significantly induced by hemolysate in a dose-dependent way in neurons. Knockdown of REDD1 by lentivirus encoded REDD1-shRNA could inhibit the neuronal apoptosis and LDH leakage caused by hemolysate. Importantly, the level of REDD1 in peripheral blood of SAH patients was significantly higher (4.364 ng/ml) than that of healthy persons (1.317 ng/ml) and also was positively correlated with that in CSF. Taken together, our findings provide the novel and direct evidence that REDD1 could play a critical role of process of neuronal damage caused by SAH, suggesting a new molecular target to protect brain function from SAH injury.

Gastric cancer is one of the leading causes of cancer-related deaths worldwide, and mortality remains high, especially in East Asia. At present, the main method to diagnose gastric cancer is pathological biopsy. At the time of diagnosis, most patients have been diagnosed with advanced cancer and metastasis. The treatment of gastric cancer patients is mainly radical surgical resection and chemoradiotherapy, while patients with metastatic tumor have great challenges to radical surgery and are prone to drug resistance. Metastasis is an important factor affecting tumor development. In addition, evidence accumulated in the literature indicates that non-coding RNA plays a key role in tumor metastasis. This article reviews the role of ncRNAs in gastric cancer metastasis and discusses the regulatory mechanism in the development and treatment of gastric cancer.

Long non-coding RNAs (lncRNAs) have emerged as important roles in gastric cancer (GC). However, the role of the dysregulated lncRNAs in GC remained large unknown. We investigated the clinical significance, biological function and mechanism of CTC-497E21.4 in GC. Firstly, RTFQ-PCR was used to detect the expression of CTC-497E21.4 in GC. Furthermore, knockdown of CTC-497E21.4 was conducted to assess the effect of CTC-497E21.4 in vitro and vivo. Subcellular localization of CTC-497E21.4 was determined by nuclear plasmolysis PCR and FISH. We also predicted CTC-497E21.4 binding miRNAs and downstream target genes and evaluated its regulation of miR-22 by acting as a ceRNA. CTC-497E21.4 was upregulated in GC tissues and GC cell lines (P

Early diagnosis of gastric cancer (GC) is an effective method to improve prognosis. Increasing number of long noncoding RNAs (lncRNAs) have been reported as biomarkers for several cancers. We aim to detect the level of lncRNA B3GALT5-AS1 and its association with clinical parameters and to further explore its application value in GC. We measured serum B3GALT5-AS1 expression in 107 patients with GC, 40 polyp patients, and 87 normal controls to explore the significance of serum B3GALT5-AS1 in GC using the quantitative real-time polymerase chain reaction method. The result demonstrated that B3GALT5-AS1 level was markedly richer in GC patients than that in normal people (P < .001). B3GALT5-AS1 may be served as a diagnostic marker for distinguishing GC patients from healthy people, and the proportion under the receiver operating characteristics curve is 0.816 (95% confidence interval, 0.758-0.874; P = .03). Further exploration validated that high serum B3GALT5-AS1 level was related to TNM stage (P = .024), and lymph node metastasis (P = .023). Our study suggested that serum B3GALT5-AS1 may be employed as an ideal biomarker for early screening of GC.

Atherosclerosis is a chronic inflammatory disease with lipid accumulation. Apolipoprotein C3 (APOC3), which is an important regulator of human lipid metabolism, is associated with multiple vascular mechanisms in atherosclerosis and proinflammatory responses. We have previously reported that the expression of inflammatory cytokine TNF-α is elevated in human endothelial cells (HUVECs) after APOC3 treatment. This study investigates the APOC3 signaling pathway involved in TNF-α-mediated expression of JAM-1 in HUVECs. Cultured HUVECs were exposed to APOC3 (50 μg/ml) for 16 h. Mechanistic studies were carried out by silencing TNF-α gene with lentiviral TNF-α-shRNA. Our study was based on the eight signaling pathway inhibitors to block the effect of APOC3 in HUVECs. The expression of JAM-1 was determined by qRT-PCR, Western blotting, and flow cytometry. IKK2 degradation and NF-κB p65 phosphorylation were determined by Western blotting. Our results showed that APOC3 significantly promoted the TNF-α-induced expression of JAM-1 in HUVECs. Inhibiting APOC3 reversed the TNF-α-induced overexpression of JAM-1. Moreover, APOC3 induced the expression of NF-κB p65 and degraded IκB. In conclusion, APOC3 promoted the expression of JAM-1 via the NF-κB, IKK2, and PI3K signaling pathway.

Alu elements are one of most ubiquitous repetitive sequences in human genome, which were considered as the junk DNA in the past. Alu elements have been found to be associated with human diseases including cancers via events such as amplification, insertion, recombination or RNA editing, which provide a new perspective of oncogenesis at both DNA and RNA levels. Due to the prevalent distribution, Alu elements are widely used as target molecule of liquid biopsy. Alu-based cell-free DNA shows feasible application value in tumour diagnosis, postoperative monitoring and adjuvant therapy. In this review, the special tumourigenesis mechanism of Alu elements in human cancers is discussed, and the application of Alu elements in various tumour liquid biopsy is summarised.

Mounting evidence has illustrated the vital roles of long non‐coding RNAs (lncRNAs in gastric cancer (GC). Nevertheless, the majority of their roles and mechanisms in GC are still largely unknown. In this study, we investigate the roles of lncRNA SLC25A5‐AS1 on tumourigenesis and explore its potential mechanisms in GC. The results showed that the expressions of SLC25A5‐AS1 in GC were significantly lower than that of adjacent normal tissues, which were significantly associated with tumour size, TNM stage and lymph node metastasis. Moreover, SLC25A5‐AS1 could inhibit GC cell proliferation, induce G1/G1 cell cycle arrest and cell apoptosis in vitro, as well as GC growth in vivo. Dual‐luciferase reporter assay confirmed the direct interaction between SLC25A5‐AS1 and miR‐19a‐3p, rescue experiment showed that co‐transfection miR‐19a‐3p mimics and pcDNA‐SLC25A5‐AS1 could partially restore the ability of GC cell proliferation and the inhibition of cell apoptosis. The mechanism analyses further found that SLC25A5‐AS1 might act as a competing endogenous RNAs (ceRNA), which was involved in the derepression of PTEN expression, a target gene of miR‐19a‐3p, and regulate malignant phenotype via PI3K/AKT signalling pathway in GC. Taken together, this study indicated that SLC25A5‐AS1 was down‐regulated in GC and functioned as a suppressor in the progression of GC. Moreover, it could act as a ceRNA to regulate cellular behaviours via miR‐19a‐3p/PTEN/PI3K/AKT signalling pathway. Thus, SLC25A5‐AS1 might be served as a potential target for cancer therapeutics in GC.

Radiotherapy, chemotherapy, autologous/allogeneic stem cell transplantation, and targeted drug therapy are currently available therapeutic options for multiple myeloma (MM), but the clinical outcome remains unsatisfactory owing to frequent occurrence of drug resistance. Anti apoptosis is one of the main mechanisms to mediate drug resistance. Studies have shown that MCL-1 plays a key role in the growth of cancer cells “escaping” drug attacks, but the underlying mechanism remains unclear. Our previous study demonstrated that lncRNA H19 was highly expressed in the serum of MM patients. Bioinformatics predicts that miR-29b-3p is the downstream target gene, and MCL-1 is the downstream target protein of miR-29b-3p. Therefore, we speculated that MCL-1 may be involved in the occurrence of drug resistance through epigenetics. On the basis of these previous findings, the present study was intended to explore the biological function of H19, interactions between the downstream target genes, and the effect of H19 on BTZ resistance of myeloma cells. In addition, in vivo experiments we have also confirmed that H19 promoted tumor growth and may develop resistance to bortezomib partly. It was found that H19 reduced cell sensitivity to the chemotherapeutic drug BTZ by working as a miRNA sponge to inhibit the expression of miR-29b-3p, enhance MCL-1 transcriptional translation and inhibit apoptosis. These findings may help gain insights into the molecular mechanism of acquired BTZ resistance and develop new drug targets for the clinical treatment of MM.

Multiple myeloma (MM) is a hematologic malignancy characterized by unrestricted secretion of monoclonal immunoglobulin and uncontrolled plasma cell proliferation. Extra-medullary infiltration and drug resistance are two major obstacles in the treatment of MM. To solve these problems, it is necessary to elucidate the underlying pathological mechanisms and find new therapeutic targets. Noncoding RNAs (ncRNAs), which were once considered "transcriptional noise," have been recognized as crucial regulators in the process of tumorigenesis including MM. Increasing evidence has shown that ncRNAs participate in MM pathogenesis via a series of complex cellular or extracellular processes. This review article summarizes examples of ncRNAs involved in myelosis and discusses their potential as biomarkers and therapeutic targets in the diagnosis and treatment of myelosis.

Background: Schizophrenia is a severe mental disorder, which has a major impact on the quality of life and imposes a huge burden on the family. However, the pathogenesis of schizophrenia remains unclear and there are no specific biomarkers. Therefore, we intend to explore whether cf-DNA levels are related to the occurrence and development of schizophrenia.Methods: We analyzed and compared the concentration of cf-DNA in 174 SZ patients and 100 matched healthy controls by using quantitative real-time PCR by amplifying the Alu repeats.Results: We found that cf-DNA levels in peripheral blood reliably distinguished SZ patients from healthy controls (P < 0.05). The ROC analysis also supports the above conclusion. By tracking the absolute concentration of serum cf-DNA in primary cases, we found a distinct increase before treatment with antipsychotics, which decreased progressively after treatment.Conclusions: The present work indicates that cf-DNA may improve the efficiency of disease diagnosis, and the level of cf-DNA plays a predictive role in the development of schizophrenia. By evaluating the level of cf-DNA, we might play a certain role in a more reasonable and standardized clinical treatment of schizophrenia.

Background Systematic performance verification is required before a laboratory can introduce a new measure-ment procedure for reporting results of patient testing. The aim of this study was to explore the basic performance and clinical application value of KU-F10 Feces analyzer. Methods We collected 530 fecal specimens in our hospital from October 2019 to February 2020, using manual methods as the gold standard. Then we made a comprehensive evaluation from repeatability, carried pollution rate, coincidence rate of formed element, and coincidence rate of fecal occult blood test. Results The sensitivity of white blood cells was 90.3%, the specificity was 99.2%, and the coincidence rate with microscopy was 98.7%; the sensitivity of the instrument to detect red blood cells was 90.3%, the specificity was 98.2%, and the coincidence rate with microscopy was 97.7%, The sensitivity of the instrument to detect fungi is 100.0%, the specificity is 98.7%, and the coincidence rate with the microscopy is 98.7%. The sensitivity of the in-strument to detect fat globules is 94.7%, the specificity is 99.0%, the coincidence rate with the microscopy is 98.9%. Comparison of instrumental fecal occult blood test and reagent B fecal occult blood result: On the 387 cases tested fecal samples, the sensitivity of the instrument was 83.8%, the specificity was 96.5%, and the coincidence rate with the results of microscopy was 92.3%. FOB minimum detection limit is 0.1 µg/mL and detection range is 0.1 to 2,000 µg/mL. Conclusions The KU-F10 feces analyzer has an advantage of a high degree of automation, simple operation procedures, fast detection speed, improved working environment, improved work efficiency, and higher clinical application value.

Exosomes are a group of nano-sized membrane vesicles and are important mediators of intercellular communication, particularly in tumor microenvironment. Recently, researchers have found that circular RNAs (circRNAs), with the great research significance, are enriched and stable in exosomes. In this review, we summarize the research significance of exosomal circRNAs, sorting mechanisms and their functioning mechanisms in tumor progression. Their clinical applications as clinical tumor biomarkers and as therapeutic targets in inhibiting tumor metastasis, anti-cancer immunity response and drug resistance have been widely discussed.

The prevalence of antibiotic resistance is a growing worldwide problem in the control of pathogens, particularly negative bacteria that are resistant to antibiotics, Pseudomonas aeruginosa (PA) is one of these bacteria. The development of new effective antibiotics is time-consuming and costly, and the new antibiotics may become resistant again. Therefore, non-antibiotic clinical treatment for antibiotic-resistant PA infection is necessary and needs to be strengthened. The antibiotic resistance (AR) mechanism of PA is complex. Biofilm formation is one of the reasons why its resistance is difficult to overcome. The formation of biofilms is mainly regulated by quorum sensing (QS). QS is a mechanism by which PA increases its virulence by producing small diffusible molecules, which regulates a series of genes associated with virulence and nutrient acquisition. QS inhibitors are potions that obstruct QS systems in bacteria and destruction of virulence. This review summarizes AR mechanism of PA, Basic knowledge of QS of PA and some non-antibiotic methods for inhibiting PA, including QS inhibitors, which have potential and far-reaching significance for antibiotic-resistant PA's clinical treatment. The review helps to provide new ideas and new schemes for clinical anti-PA infection research and treatment, and has positive significance for delaying the occurrence of bacterial drug resistance and antibiotic use management.

Background Gastric cancer (GC) is one of the most common cancers in the world. Due to the lack of specific symptoms, more than 80% of patients are diagnosed as the advanced stage with a high mortality rate, so the early diagnosis of GC is incredibly essential. Circular RNAs (CircRNAs) are a kind of endogenous non-coding RNA with stable structure, the long half-life, and tumor specificity. It can be used as a diagnostic marker for tumors. Method Using circRNA sequencing technology screened three pairs of GC and adjacent tissues, and circRNAs with significant expression differences were screened out. The circular structure and characteristics of circPTPN22 were determined by RT-qPCR, agarose gel electrophoresis, Sanger sequencing, RNase R, and actinomycin D assays. Cell Counting Kit‐8, colony formation, Transwell, Wound healing, tumor formation in mice and western blotting assays were used to detect the effects of circPTPN22 on the proliferation, invasion, migration, tumor growth of GC cells in vitro and protein expression. Result CircPTPN22 is up-regulated and positively correlated with metastasis in GC tissues, cells, and plasma. RT-qPCR results showed that circPTPN22 had good diagnostic efficacy and could be used to predict the prognosis of GC patients. In vitro and vivo experiments showed that the downregulation of circPTPN22 could inhibit cell proliferation, migration, and invasion through the epithelial-mesenchymal transformation (EMT) pathway. CircPTPN22 may regulate GC progression through the competitive binding of miRNAs. Conclusion CircPTPN22 can be used as a potential diagnostic and prognostic marker for GC and can inhibit cell proliferation and metastasis through the competitive binding of miRNA to inhibit the EMT pathway.

Although accumulating documents have expounded the pivotal position of circular RNAs (circRNAs) in hepatocarcinogenesis and progression, the overwhelming majority of their functions and molecular mechanisms in hepatocellular carcinoma (HCC) are elusive. Herein, we explored the functions and potential mechanisms of hsa_circ_0005785 in HCC, which was aberrantly overexpressed in HCC and related to HCC patients' TNM stage and overall survival. Moreover, hsa_circ_0005785 depletion could repress proliferation and metastasis of the HCC cell in vitro, lead to cell apoptosis and cell-cycle arrest, and restrain HCC cell growth in vivo. Furthermore, mechanism analyses discovered that hsa_circ_0005785 adsorbed miR-578 by playing a miRNA sponge role, which resulted in the derepression of a proliferation-inducing ligand (APRIL) expression, miR-578's mRNA target. Besides, hsa_circ_0005785 reversed the suppressive influence of miR-578 on HCC and accelerated tumor malignant progression through the miR-578/APRIL axis. Taken together, our current study revealed an oncogenic role of hsa_circ_0005785 in the tumorigenesis of HCC. Moreover, targeting to the hsa_circ_0005785/miR-578/APRIL regulatory pathway might be a promising diagnostic and therapeutic strategy for HCC clinical practice.

In recent years, the prevalence and spread of coronavirus has had a huge impact on global public health. Due to the incomplete understanding of the pathogenic mechanism of the virus, it is difficult for humans to fight against the virus quickly and effectively once the outbreak occurs. In early 2020, a novel coronavirus was discovered in Wuhan, China. Soon after, similar cases were found in other countries around the world, and the number of infected people increased rapidly. So far, the global cumulative number of infected people has exceeded 3 million, and more than 200,000 people have died, which has had a huge impact on global human health and economic development. Every outbreak of disease makes a deep impression on mankind. Herein, we summarize the virology, epidemiology, clinical manifestations, diagnosis, treatment and prevention of SARS-CoV-2, and hope that countries can control the outbreak as soon as possible to minimize the loss.

Pancreatic ductal adenocarcinoma (PDAC) will become the second most common cause of death in North America and Europe over the next 10 years owing to the lack of early diagnosis, poor treatment, and poor prognosis. This study evaluated the methylation array data of 184 patients with PDAC in The Cancer Genome Atlas database to explore methylation biomarkers related to patient outcome. Using Univariable Cox regression analysis and Lasso regression analysis method in the training dataset, it was found that the four DNA methylation markers (CCNT1, ITGB3, SDS, and HMOX2) were significantly correlated with the overall survival of patients with PDAC. Kaplan-Meier analysis showed that these four DNA methylation markers could significantly distinguish high-risk and low-risk patients. Receiver operating characteristic analysis further confirmed that the four DNA methylation markers had high sensitivity and specificity, which could predict the prognosis of patients. Moreover, there was a difference in the genetic mutations between high-risk and low-risk patients distinguished by the four-DNA methylation model, which can provide information for clinical treatment. Finally, compared with known biomarkers, the model was more accurate in predicting the prognosis of PDAC. This four-DNA methylation model has potential as a new independent prognostic indicator, and could be used for the diagnosis, monitoring, and precision medicine of pancreatic cancer.

Gastric cancer (GC) is one of malignant tumor with the highest incidence and mortality in the world. The long noncoding RNA (lncRNA) play an important role in GC. We aim to systematically evaluate the clinical values of lncRNA RP11-731F5.2 in GC.We evaluated the level of serum RP11-731F5.2 by the reverse transcription and quantitative real-time PCR. The study involved following aspects: (1) confirmation of the higher RP11-731F5.2 level in serum specimens of GC; (2) evaluation of efficacy monitoring value by the serum RP11-731F5.2 assay in GC; (3) evaluation of the prognostic value by the serum RP11-731F5.2 assay in GC.The level of RP11-731F5.2 stably present in the serum of GC patients (median [interquartile range, IQR 25-75]: 1.495 [0.912-2.367]) was significantly higher than that in healthy controls (0.620 [0.400-1.222]) (P 0.001). Combined with RP11-731F5.2, CEA and CA19-9, the area under the curve was the largest (0.84, 95 % confidence interval, 0.77-0.90), which can significantly improve the diagnostic efficacy of GC. Moreover, the level of serum RP11-731F5.2 in postoperative samples decreased significantly compared with the level of preoperative samples (2.415 [1.558-3.115] versus 2.007 [1.112-2.711], P = 0.029). There was difference in survival time between GC patients containing higher level of RP11-731F5.2 and those with lower level of RP11-731F5.2 (P = 0.048).Our study suggested that circulating RP11-731F5.2 may be employed as a novel diagnostic, efficacy monitoring and prognostic biomarker for GC.

N6-methyladenosine (m6A) is considered the most common, abundant, and conserved internal transcript modification, especially in eukaryotic messenger RNA (mRNA). m6A is installed by m6A methyltransferases (METTL3/14, WTAP, RBM15/15B, VIRMA and ZC3H13, termed “writers”), removed by demethylases (FTO, ALKBH5, and ALKBH3, termed “erasers”), and recognized by m6A-binding proteins (YTHDC1/2, YTHDF1/2/3, IGF2BP1/2/3, HNRNP, and eIF3, termed “readers”). Accumulating evidence suggests that m6A RNA methylation greatly impacts RNA metabolism and is involved in the pathogenesis of many kinds of diseases, including cancers. In this review, we focus on the physiological functions of m6A modification and its related regulators, as well as on the potential biological roles of these elements in human tumors.

Studies have shown that long non-coding RNAs (lncRNAs) play vital roles in the development of cancer, including colorectal cancer (CRC). Our purpose is to validate the diagnostic value of serum differentiation antagonizing non-protein coding RNA (DANCR) in CRC by focusing on its expression and clinical application. lncRNA expression profiles of CRC patients were obtained and analyzed by repurposing the publically available microarray data. Tissue or serum specimens were obtained from 40 patients with primary CRC, 10 patients with recurrent CRC, 40 patients with colorectal polyps, and 40 healthy controls. It was found that DANCR level in the CRC tissue and serum was significantly increased, and serum DANCR expression was decreased in post-operative patients as compared with that in pre-treatment patients and recurrent patients. In addition, serum DANCR expression was significantly correlated with different TNM stages. Correlation analysis of DANCR and other diagnostic indicators showed that the serum DANCR expression level was significantly correlated with CA199 but not with CEA in CRC patients. As for diagnostic efficiency by ROC analysis, the area under the curve (AUC) of serum DANCR was higher than that of CEA and CA199 in CRC group vs. colorectal polyp group. Simultaneous detection of DANCR, CEA and CA199 yielded the highest sensitivity and AUC as compared with either of them alone. Taken together, serum DANCR was up-regulated in CRC patients and high expression of DANCR may prove to be a potential biomarker for the diagnosis of CRC.

Psychiatric disorders impose a huge burden on individuals, families, and society. The Alu repeat sequence is a member of the short interspersed nuclear element (SINE) family of mammalian genomes, however, its expression pattern and role in psychiatric disorders is unclear. The current paper aimed at determining the concentrations of Alu in patients with schizophrenia (SZ), major depressive disorder (MDD), and alcohol-induced psychotic disorder (AIPD), and to further define the role and value of Alu as a potential biomarker in psychiatric disorders. In this work, we found that the concentration of Alu was considerably incremented in patients with SZ, and a significant difference existed between patients diagnosed with SZ and MDD or AIPD. ROC analysis also indicated that Alu was effective in the complementary diagnosis of SZ, and differentially diagnosed between SZ patients and patients with MDD or AIPD. In addition, we found a positive relationship between the Alu concentrations and interleukin-1β (IL-1β) in patients with SZ, MDD, and AIPD, and between the concentrations of Alu and interleukin-18 (IL-18) in patients with SZ. Overall, the present work indicates that Alu might be an innovative biomarker for diagnosing psychiatric disorders, and provides the basis for hypotheses about the pathophysiology of psychiatric disorders.

BACKGROUND Carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are the most commonly used tumor markers in gastric cancer (GC). The purpose of this study was to dynamically monitor the preoperative and postoperative CEA and/or CA19-9 levels in GC patients to determine their value in efficacy monitoring and prognosis. METHODS The preoperative and postoperative CEA and/or CA19-9 were measured in 397 GC patients and correlated to pathology and the overall survival (OS). RESULTS We found the depth of invasion, lymph node metastasis, and pTNM stage were the most important factors affecting the elevated levels of CEA and CA19-9 in GC patients (all p < 0.001). There were significant differences between preoperative CEA or CA19-9 and postoperative values (p < 0.001). Multivariate analyses revealed that postoperative CEA and the presence of lymph node metastasis were independently associated with shorter OS (p = 0.041; p = 0.030). CONCLUSIONS Dynamic monitoring of CEA and CA19-9 before and after surgery can be used to determine tumor burden. Postoperative rather than preoperative tumor markers, especially postoperative CEA, are good indicators for judging the prognosis of GC patients.

Growing evidence indicates that the tumor biomarker cytokeratin 19 fragment (CYFRA21-1) is significant for a variety of cancers. However, its role in epithelial ovarian cancer (EOC) has rarely been reported. In this study, a receiver operating characteristic (ROC) curve was utilized to estimate the diagnostic efficiency of CYFRA21-1. The correlation between the CYFRA21-1 level and prognosis was analyzed by Kaplan-Meier survival analysis and univariable and multivariable analyses. The relationship between serum CYFRA21-1 levels and different clinicopathological variables was also analyzed. At the same time, the standard serum marker cancer antigen 125 (CA125) was measured. The results demonstrated that CYFRA21-1 expression was significantly increased in EOC compared with expression in benign ovarian diseases and healthy controls, which was similar to CA125 (P P = 0.0032). CYFRA21-1 expression was significantly correlated with lymph node metastasis and ascites (P P

Gastric cancer (GC) is one of the most common cancers globally. Because of the high frequency of tumor recurrence, or metastasis, after surgical resection, the prognosis of patients with GC is poor. Therefore, exploring the mechanisms underlying GC is of great importance. Recently, accumulating evidence has begun to show that dysregulated long non-coding RNAs (lncRNAs) participate in the progression of GC via several typical signaling pathways, such as the AKT and MAPK signaling pathways. Moreover, the interactions between lncRNAs and microRNAs appear to represent a novel mechanism in the pathogenesis of GC. This review provides a synopsis of the latest research relating to lncRNAs and associated signaling pathways in GC.

Circulating long noncoding RNA (lncRNA) H19 has been reported to be a biomarker for cancer monitoring. The purpose of this study was to determine whether serum lncRNA could serve as a novel biomarker for the diagnosis of multiple myeloma (MM) and evaluate its value of clinical application. In our study, the expression of lncRNA H19 was up-regulated in 80 patients with MM and MM cell lines by RT-PCR analysis. Clinicopathological analysis showed the expression level of H19 could assist clinical staging, and the severity of the disease could be roughly determined according to the amount of H19 expressed in the patient serum. This is the first report to show that H19 was expressed in the serum of MM patients, suggesting that upregulation of serum lncRNA H19 may prove to be a novel biomarker for early diagnosis and clinical treatment of MM.

Lung cancer, particularly non-small cell lung cancer (NSCLC), is one of main causes of mortality in cancer patients worldwide. It is necessary to seek effective biomarkers to improve diagnostic and therapeutic efficacies in human NSCLC. RTP801 is a stress-response protein that can be induced by many types of cellular stress such as hypoxia and DNA damage, produces different biological effects depending on cell type and context. Up to now, there is no direct evidence showing the expression and involvement of RTP801 in human NSCLC. Here, we found that the expression of RTP801 significantly increased in NSCLC tissues compared with that in normal lung and the level of RTP801 in peripheral blood of NSCLC patients was higher than that of healthy persons. Further study showed that knockdown of RTP801 induced by lentivirus encoded RTP801-shRNA markedly inhibited the proliferation of A549 and SW900 cells. Moreover, the inhibitor of PI3K significantly decreased the expression of RTP801 mRNA and protein and, at the same time, inhibited the proliferation of A549 and SW900 cells. Taken together, our study provides the novel and direct evidence that there is a close relationship between RTP801 and human NSCLC, and RTP801 can promote the proliferation of NSCLC cells which is regulated by PI3K signaling pathway, suggesting that RTP801 could be a potential biomarker for diagnosis and therapeutic target of human NSCLC. © 2018 IUBMB Life, 70(4):310-319, 2018.

Circulating tumor cells (CTCs) exist in the peripheral blood and have an important role in the disease development, tumor metastasis and clinical surveillance, especially in the process of metastasis. However, the technology of detecting CTCs still had a large challenge since they were rare in the peripheral blood. Here, we developed a size-based microfluidic chip, which contained array and filter channel array that could enrich CTCs from blood samples more quickly and conveniently. Combined with clinical specimen, we analyzed CTCs in 200 lung cancer patients by this microfluidic chip. The microfluidic device has high specificity and sensitivity in detecting CTCs (86.0% sensitivity and 98% specificity). Furthermore, the number of CTCs showed a increasing trend according to the stage of the disease (the mean number of I stage 5.0 ± 5.121 versus II stage 8.731 ± 6.36 versus III stage 16.81 ± 9.556 versus IV stage 28.72 ± 17.39 cells/mL, P