Determination of reference intervals of serum levels of human epididymis protein 4 (HE4) in Chinese women

The detailed numbers of subjects from different centers. (DOCX 17.3 kb

The Potential Role of ORM2 in the Development of Colorectal Cancer

Colorectal cancer (CRC) is the third most common malignancy in the world. The risk of death is closely correlated to the stage of CRC at the time of primary diagnosis. Therefore, there is a compelling need for the identification of blood biomarkers that can enable early detection of CRC. We used a quantitative proteomic approach with isobaric labeling (iTRAQ) to examine changes in the plasma proteome of 10 patients with CRC compared to healthy volunteers. Enzyme-Linked Immunosorbnent Assay (ELISA) and Western blot were used for further validation. In our quantitative proteomics analysis, we detected 75 human plasma proteins with more than 95% confidence using iTRAQ labeling in conjunction with microQ-TOF MS. 9 up-regulated and 4 down-regulated proteins were observed in the CRC group. The ORM2 level in plasma was confirmed to be significantly elevated in patients suffering from CRC compared with the controls. ORM2 expression in CRC tissues was significantly increased compared with that in corresponding adjacent normal mucous tissues (P<0.001). ITRAQ together with Q-TOF/MS is a sensitive and reproducible technique of quantitative proteomics. Alteration in expression of ORM2 suggests that ORM2 could be used as a potential biomarker in the diagnosis of CRC

Comprehensive analysis of m6A regulators and relationship with tumor microenvironment, immunotherapy strategies in colorectal adenocarcinoma

Abstract Background The N6-methyladenosine (m6A) RNA modification is the most prevalent and abundant type found in eukaryotic cells. It plays a crucial role in the initiation and progression of cancers. In this study, we aimed to comprehensively investigate the landscape of m6A regulators and their association with tumor microenvironment (TME), immunotherapeutic strategies in colon adenocarcinoma (COAD). Results The differential expression, mutation, CNV frequency and prognostic value of 27 m6A regulators were systematically analyzed in COAD. Patients were classified into two clusters based on m6A regulators through consistent clustering analysis, with cluster A showing significant survival benefits. Most of the m6A regulators were negatively correlated with immune cells, except for WTAP, IGF2BP3, FTO, ALKBH5, which showed a positive correlation. We developed an m6A scoring system to calculate the m6Ascore for each patient. Patients with a high-m6Ascore had a better outcome, with the AUC of 0.775. An independent cohort of 416 COAD patients acquired from GSE38832 database was used to validate the prognosis prediction ability of m6Ascore. Moreover, the m6Ascore was negatively correlated with infiltration of anti-tumor immune cells. Additionally, patients with a high-m6Ascore responded better to anti-PD1 and anti-CTLA4 therapies, and those with MSI-H had a higher m6Ascore. Finally, we investigated the value of m6Ascore in predicting the response of patients to 15 commonly used drugs. Conclusions We comprehensively analyzed m6A regulators in COAD, including RNA expression, CNV changes, mutations and their correlation with TME. Our results showed that the m6A scoring system had significant predictive power for the prognosis of COAD patients, potentially leading to new personalized immunotherapy strategies

Development of a preoperative prediction nomogram for lymph node metastasis in colorectal cancer based on a novel serum miRNA signature and CT scansResearch in context

Background: Preoperative prediction of lymph node (LN) status is of crucial importance for appropriate treatment planning in patients with colorectal cancer (CRC). In this study, we sought to develop and validate a non-invasive nomogram model to preoperatively predict LN metastasis in CRC. Methods: Development of the nomogram entailed three subsequent stages with specific patient sets. In the discovery set (n = 20), LN-status-related miRNAs were screened from high-throughput sequencing data of human CRC serum samples. In the training set (n = 218), a miRNA panel-clinicopathologic nomogram was developed by logistic regression analysis for preoperative prediction of LN metastasis. In the validation set (n = 198), we validated the above nomogram with respect to its discrimination, calibration and clinical application. Findings: Four differently expressed miRNAs (miR-122-5p, miR-146b-5p, miR-186-5p and miR-193a-5p) were identified in the serum samples from CRC patients with and without LN metastasis, which also had regulatory effects on CRC cell migration. The combined miRNA panel could provide higher LN prediction capability compared with computed tomography (CT) scans (P < .0001 in both the training and validation sets). Furthermore, a nomogram integrating the miRNA-based panel and CT-reported LN status was constructed in the training set, which performed well in both the training and validation sets (AUC: 0.913 and 0.883, respectively). Decision curve analysis demonstrated the clinical usefulness of the nomogram. Interpretation: Our nomogram is a reliable prediction model that can be conveniently and efficiently used to improve the accuracy of preoperative prediction of LN metastasis in patients with CRC. Keywords: Colorectal cancer, miRNA-based panel, LN metastasis, Prediction, Nomogra

Genome‐wide identification of a novel miRNA‐based signature to predict recurrence in patients with gastric cancer

The current tumor node metastasis (TNM) staging system is inadequate for identifying high‐risk gastric cancer (GC) patients. Using a systematic and comprehensive‐biomarker discovery and validation approach, we attempted to build a microRNA (miRNA)‐recurrence classifier (MRC) to improve the prognostic prediction of GC. We identified 312 differentially expressed miRNAs in 446 GC tissues compared to 45 normal controls by analyzing high‐throughput data from The Cancer Genome Atlas (TCGA). Using a Cox regression model, we developed an 11‐miRNA signature that could successfully discriminate high‐risk patients in the training set (n = 372; P < 0.0001). Quantitative real‐time polymerase chain reaction‐based validation in an independent clinical cohort (n = 88) of formalin‐fixed paraffin‐embedded clinical GC samples showed that MRC‐derived high‐risk patients succumb to significantly poor recurrence‐free survival in GC patients (P < 0.0001). Cox and stratification analysis indicated that the prognostic value of this signature was independent of clinicopathological risk factors. Time‐dependent receiver operating characteristic (ROC) analysis revealed that the area under the curve of this signature was significantly larger than that of TNM stage in the TCGA (0.733 vs. 0.589 at 3 years, P = 0.004; 0.802 vs. 0.635 at 5 years, P = 0.005) and validation cohort (0.835 vs. 0.689 at 3 years, P = 0.003). A nomogram was constructed for clinical use, which integrated both MRC and clinical‐related variables (depth of invasion, lymph node status and distance metastasis) and did well in the calibration plots. In conclusion, this novel miRNA‐based signature is superior to currently used clinicopathological features for identifying high‐risk GC patients. It can be readily translated into clinical practice with formalin‐fixed paraffin‐embedded specimens for specific decision‐making applications

MiR-203 suppresses ZNF217 upregulation in colorectal cancer and its oncogenicity.

Zinc finger protein 217 (ZNF217) is essential for cell proliferation and has been implicated in tumorigenesis. However, its expression and exact roles in colorectal cancer (CRC) remain unclear. In this study, we demonstrated that ZNF217 expression was aberrantly upregulated in CRC tissues and associated with poor overall survival of CRC patients. In addition, we found that ZNF217 was a putative target of microRNA (miR)-203 using bioinformatics analysis and confirmed that using luciferase reporter assay. Moreover, in vitro knockdown of ZNF217 or enforced expression of miR-203 attenuated CRC cell proliferation, invasion and migration. Furthermore, combined treatment of ZNF217 siRNA and miR-203 exhibited synergistic inhibitory effects. Taken together, our results provide new evidences that ZNF217 has an oncogenic role in CRC and is regulated by miR-203, and open up the possibility of ZNF217- and miR-203-targeted therapy for CRC

Interaction of toxin-1 and T lymphocytes in toxic shock syndrome

Toxic shock syndrome (TSS) is a potentially fatal illness caused by infection with the bacterium Staphylococcus aureus. TSS toxin-1 (TSST-1) contains a T-cell epitope with specificity for human V-beta-2. Binding of TSST-1 to the human major histocompatibility complex and T cell receptors activates T cells and triggers the secretion of high amounts of inflammatory cytokines, leading to TSS and potentially death. During this process, CD4(+) T cells are inhibited by TSST-1, while regulatory T cells are increased. This suggests a protective immune response by the body in TSS. Thus, TSST-1 can trigger both, an inflammatory response that attacks the body and a protective response. In this review, we discuss the interaction between TSST-1 and T lymphocytes in TSS

Hypoxia-inducible MiR-210 is an independent prognostic factor and contributes to metastasis in colorectal cancer.

MicroRNA-210 (miR-210), the master hypoxamir, plays pleiotropic roles in certain cancers; however, its role in the development of human colorectal cancer remains unclear. Herein, we report that miR-210 is frequently up-regulated in colorectal cancer tissues, with high miR-210 expression significantly correlating with large tumor size, lymph node metastasis, advanced clinical stage and poor prognosis. Functionally, miR-210 overexpression promotes the migration and invasion of colorectal cancer cells. Furthermore, miR-210 can be induced by hypoxia and mediates the hypoxia-induced metastasis of colorectal cancer cells. In addition, vacuole membrane protein 1 (VMP1) is identified as the direct and functional target of miR-210. Thus, miR-210 is a useful biomarker for hypoxic tumor cells and a prognostic factor that plays an essential role in colorectal cancer metastasis

Functional effects of ZNF217 downregulation and miR-203 upregulation on SW480 cells.

<p>(A) Effective suppression of ZNF217 protein expression by ZNF217 siRNA and miR-203 mimics respectively and combinedly. Note that ZNF217 expression is more efficiently suppressed by combined treatment. Suppression of ZNF217 simultaneously resulted in (B) significant inhibition of cell growth and (C) migration and invasion (200×magnification) of SW480 cells compared with negative controls. Note the synergistic inhibitory effect of combination of ZNF217 siRNA and miR-203 mimics, compared with either of them alone (*P < 0.05).</p

Association between patients, characteristics and ZNF217 expression in 82 CRC cases.

<p>Well and moderate:well and moderately differentiated; poor: poorly differentiated</p><p>Association between patients, characteristics and ZNF217 expression in 82 CRC cases.</p