Advanced gastric cancer with metachronous intracranial oligometastases without recurrence after multidisciplinary team discussion and comprehensive treatment: a case report.

This article describes the process of multidisciplinary team (MDT) discussion and comprehensive treatment of a case of advanced gastric cancer that tested positive for programmed death ligand 1 (PD-L1). During diagnosis, the patient presented with advanced gastric cancer and numerous unresectable metastases in the lesser omental lymph nodes, both lungs, liver, and left parietal occipital lobe. A meeting was arranged for the departments of oncology, gastrointestinal surgery, radiotherapy, imaging, and pathology to discuss the case. Initially, the patient had a partial response to the first-line treatment, which was a combination of pembrolizumab and chemotherapy. However, after nineteen months, the patient presented with a metachronous isolated lesion in the left frontal lobe. After mutual agreement among the oncology, brain surgery, gastrointestinal surgery, radiotherapy, imaging, and pathology departments, the intracranial lesion underwent resection. Following this, the operation was supplemented by stereotactic radiation therapy (SRT) and whole-brain radiation therapy (WBRT). The patient showed excellent signs of recovery after the operation, and her general condition remained favorable after 16 months of follow-up. Nonetheless, the outlook for patients facing advanced-stage gastric cancer remains distressing. Through multidisciplinary team (MDT) discussions, patients diagnosed with advanced gastric cancer can receive standardized diagnostic and treatment approaches to develop reasonable and personalized comprehensive treatment plans. Such plans help to improve the quality of life of patients and effectively prolong their survival time.

Targeting Strategies for Aberrant Lipid Metabolism Reprogramming and the Immune Microenvironment in Esophageal Cancer: A Review.

Esophageal cancer is of high importance to occurrence, development, and treatment resistance. As evidenced by recent studies, pathways (e.g., Wnt/ß-catenin, AMPK, and Hippo) are critical to the proliferation, differentiation, and self-renewal of esophageal cancer. In addition, the above pathways play a certain role in regulating esophageal cancer and act as potential therapeutic targets. Over the past few years, the function of lipid metabolism in controlling tumor cells and immune cells has aroused extensive attention. It has been reported that there are intricate interactions between lipid metabolism reprogramming between immune and esophageal cancer cells, whereas molecular mechanisms should be studied in depth. Immune cells have been commonly recognized as a vital player in the esophageal cancer microenvironment, having complex crosstalk with cancer cells. It is increasingly evidenced that the function of immune cells in the tumor microenvironment (TME) is significantly correlated with abnormal lipid metabolism. In this review, the latest findings in lipid metabolism reprogramming in TME are summarized, and the above findings are linked to esophageal cancer progression. Aberrant lipid metabolism and associated signaling pathways are likely to serve as a novel strategy to treat esophageal cancer through lipid metabolism reprogramming.

The Role of Lipid Metabolism in Gastric Cancer.

Gastric cancer has been one of the most common cancers worldwide with extensive metastasis and high mortality. Chemotherapy has been found as a main treatment for metastatic gastric cancer, whereas drug resistance limits the effectiveness of chemotherapy and leads to treatment failure. Chemotherapy resistance in gastric cancer has a complex and multifactorial mechanism, among which lipid metabolism plays a vital role. Increased synthesis of new lipids or uptake of exogenous lipids can facilitate the rapid growth of cancer cells and tumor formation. Lipids form the structural basis of biofilms while serving as signal molecules and energy sources. It is noteworthy that lipid metabolism is capable of inducing drug resistance in gastric cancer cells by reshaping the tumor micro-environment. In this study, new mechanisms of lipid metabolism in gastric cancer and the metabolic pathways correlated with chemotherapy resistance are reviewed. In particular, we discuss the effects of lipid metabolism on autophagy, biomarkers treatment and drug resistance in gastric cancer from the perspective of lipid metabolism. In brief, new insights can be gained into the development of promising therapies through an in-depth investigation of the mechanism of lipid metabolism reprogramming and resensitization to chemotherapy in gastric cancer cells, and scientific treatment can be provided by applying lipid-key enzyme inhibitors as cancer chemical sensitizers in clinical settings.

The Involvement of WDHD1 in the Occurrence of Esophageal Cancer as a Downstream Target of PI3K/AKT Pathway.

Esophageal cancer is one of the most common malignant tumors in the world, which is characterized by high incidence, strong invasiveness, high mortality, and poor prognosis. At present, the therapies include surgery, endoscopic resection, radiotherapy and chemotherapy, targeted therapy, and immunotherapy. The five-year survival rate of esophageal cancer has not been significantly improved, although the medical level has been continuously improved and the management and application of different therapies have been improved day by day. At present, an abnormal gene expression is still regarded as an important factor in the occurrence and development of esophageal cancer. WD repeat and HMG-box DNA binding protein 1(WDHD1), as a key gene, plays an important role in the occurrence of esophageal cancer. It is known that the protein encoded by WDHD1 is the downstream target of the PI3K/AKT pathway. When PI3Ks is activated by extracellular signals, PI(4,5)P2 on the inner side of the plasma membrane will be converted into PI(3,4,5)P3. Then, PI(3,4,5)P3 can be converted into PI(3,4)P2,PI(4)P and PI(3)P by dephosphorylation of some regulatory factors. PI(3,4,5)P3 recruited AKT to the plasma membrane and combined with its pH domain, resulting in conformational change of AKT. Subsequently, AKT was completely activated by PDK1 and PDK2 and begins to move to the cytoplasm and nucleus. In this process, AKT continuously phosphorylates downstream substrates. WDHD1, as a downstream target of AKT, is also phosphorylated and induces DNA replication. Besides the abnormal regulation of cells by other downstream targets of AKT, it also becomes a potential pathway that may eventually lead to the occurrence of esophageal cancer.

Identification of Differentially Expressed Genes Related to the Lipid Metabolism of Esophageal Squamous Cell Carcinoma by Integrated Bioinformatics Analysis.

Purpose: In recent years, lipid metabolism has been reprogrammed to meet the energy and substrate needs of tumorigenesis and development and is a potential new target for cancer treatment. However, the regulatory mechanism of lipid metabolism in esophageal squamous cell carcinoma is not well understood. Methods: We first downloaded the esophageal squamous cell carcinoma (ESCC) gene dataset in the GEO and TCGA databases and analyzed the central differentially expressed genes (DEGs) of ESCC through bioinformatics. Afterwards, the GSEA method was used to analyze the lipid metabolism-related pathway of the central gene in the pathological process of ESCC, and it was determined that the central gene OIP5 was significantly related to the fatty acid metabolism pathway. Our heatmap also revealed that the enrichment of the ACSL family in ESCC tissues was more pronounced than in normal tissues. We hypothesized that OIP5 can regulate the fatty acid metabolism process in ESCC cells and affect the tumorigenic ability of ESCC. Further statistical analysis and experiment were conducted to determine the lipid metabolism-related gene, OIP5's, expression pattern and clinical significance in ESCC, analyze the effect of OIP5 expression on fatty acid metabolism-related enzymes in ESCC, revealing the specific mechanism of OIP5 that promotes ESCC development. Conclusions: Our study established a correlation between OIP5 expression and clinicopathological factors (tumor size, T stage, N stage, and clinical grade) in esophageal squamous cell carcinoma (p < 0.05). We have also experimentally demonstrated that OIP5 regulates ESCC fatty acid metabolism by influencing the expression of the key enzyme ACSL1 in lipid metabolism.

m6A Methyltransferase 3 Promotes the Proliferation and Migration of Gastric Cancer Cells through the m6A Modification of YAP1.

Gastric cancer is the most common gastrointestinal tumor with an increasing incidence. Furthermore, advanced gastric cancer is more common, but the mechanism underlying the proliferation and metastasis of gastric cancer has not been thoroughly explored. N6-methyladenosine (m6A) methyltransferase 3 (METTL3) may be involved in the proliferation and metastasis of gastric cancer. Therefore, Yes-associated protein 1 (YAP1) in the Hippo pathway was selected as the target, and the relationship between METTL3 and the proliferation and metastasis of gastric cancer was proved through a series of experiments. This research showed that the expression of m6A and METTL3 was upregulated in human gastric cancer tissues and gastric cancer cell lines. After lentiviral transfection, METTL3 silencing in AGS (human gastric adenocarcinoma cell line AGS) and MKN-45 (human gastric cancer cell line MKN-45) gastric cancer cell lines directly inhibited the proliferation, aggressiveness, and migration of gastric cancer cells. Mechanically, the inhibition of the YAP1-TEAD signaling pathway by peptide 17 reduces m6A methylation and the total mRNA level of YAP1. It also eliminates the promoting effect of METTL3 on the proliferation and migration of gastric cancer cells. In turn, the overexpression of YAP1 eliminates the inhibitory effect of METTL3 silencing on the proliferation, migration, and invasion of gastric cancer cells. This article proved that m6A methyltransferase METTL3 promoted the proliferation and migration of gastric cancer cells through the m6A modification of YAP1.

MicroRNA panel in serum reveals novel diagnostic biomarkers for prostate cancer.

PURPOSE: MicroRNAs (miRNAs), which could be stably preserved and detected in serum or plasma, could act as biomarkers in cancer diagnosis. Prostate cancer is the second cancer in males for incidence. This study aimed to establish a miRNA panel in peripheral serum which could act as a non-invasive biomarker helping diagnosing PC. METHODS: A total of 86 PC patients and 86 normal control serum samples were analyzed through a four-stage experimental process using quantitative real-time polymerase chain reaction. Logistic regression method was used to construct a diagnostic model based on the differentially expressed miRNAs in serum. Receiver operating characteristic curves were constructed to evaluate the diagnostic accuracy. We also compared the 3-miRNA panel with previously reported biomarkers and verified in four public datasets. In addition, the expression characteristics of the identified miRNAs were further explored in tissue and serum exosomes samples. RESULTS: We identified a 3-miRNA signature including up-regulated miR-146a-5p, miR-24-3p and miR-93-5p for PC detection. Areas under the receiver operating characteristic curve of the 3-miRNA panel for the training, testing and external validation phase were 0.819, 0.831 and 0.814, respectively. The identified signature has a very stable diagnostic performance in the large cohorts of four public datasets. Compared with previously identified miRNA biomarkers, the 3-miRNA signature in this study has superior performance in diagnosing PC. What's more, the expression level of miR-93-5p was also elevated in exosomes from PC samples. However, in PC tissues, none of the three miRNAs showed significantly dysregulated expression. CONCLUSIONS: We established a three-miRNA panel (miR-146a-5p, miR-24-3p and miR-93-5p) in peripheral serum which could act as a non-invasive biomarker helping diagnosing PC.

Aberrant lipid metabolism reprogramming and immune microenvironment for gastric cancer: a literature review.

OBJECTIVE: We summarize the aberrant lipid metabolism disorders associated with enzyme activity and expression changes and related immune microenvironment for gastric cancer. BACKGROUND: Gastric cancer is a malignant tumor of the primary digestive system with high incidence, poor prognosis characterized by extensive metastasis and poor effect with radiotherapy and chemotherapy. One of the most important metabolic characteristics of cancer cells is lipid metabolism reprogramming to adapt to the tumor micro-environment. METHODS: The focus of research in recent years has also been on lipid metabolism disorders, particularly aberrant metabolism of fatty acids (FAs) in gastric cancer cells, as well as an upregulation of the expression and activity of key enzymes in lipid metabolism. These changes remind us of the occurrence and development of gastric cancer. These metabolic changes are not unique to cancer cells. Changes in metabolic procedures also determine the function and viability of immune cells. In the immune microenvironment of gastric cancer, the metabolic competition and interaction between cancer cells and immune cells are not very clear, while a deeper understanding of the topic is critical to targeting the differential metabolic requirements of them that comprise an immune response to cancer offers an opportunity to selectively regulate immune cell function. CONCLUSIONS: Recent research suggests that targeting metabolism is an emerging and potentially promising treatment strategy for gastric cancer patients. We need to explore it further.

The Prognostic Value of the Prognostic Nutritional Index (PNI) in Radically Resected Esophagogastric Junction Adenocarcinoma.

To determine the influence of preoperative prognostic nutritional index in adenocarcinoma of the esophagogastric junction, this study was conducted to analyze 420 patients with adenocarcinoma of the esophagogastric junction who underwent surgery. A total of 120 healthy volunteers were included as the healthy control group. The cutoff values of prognostic nutritional index for predicting survival were obtained according to the receiver operating characteristic curve. The clinic-pathological feature and survival were compared between low and high prognostic nutritional index group. Results showed that the prognostic nutritional index in the patient group was lower than that in the healthy control group (P < 0.05). The level of prognostic nutritional index was significantly associated with tumor differentiation, Siewert type, tumor size, body mass index, and hemoglobin levels (P < 0.05). The level of prognostic nutritional index was negatively correlated with age of onset, tumor differentiation, Siewert type, tumor size, depth of tumor, but positively associated with the levels of body mass index and hemoglobin. Multivariate analysis revealed that prognostic nutritional index was an independent factor associated with disease-free survival (P = 0.027) and overall survival (P = 0.003). In conclusion, low prognostic nutritional index may be considered as an independent adverse prognostic marker in patients with adenocarcinoma of the esophagogastric junction.

Knockdown of Long Non-coding RNA LINC00200 Inhibits Gastric Cancer Progression by Regulating miR-143-3p/SERPINE1 Axis.

BACKGROUND: An increasing number of studies have found that long non-coding RNAs (lncRNAs) play an important role in carcinogenesis and tumor progression, whereas their molecular mechanisms of function remain largely unknown. AIMS: This study was aimed to explore the biological function and underlying mechanism of a new lncRNA LINC00200 in gastric cancer (GC). METHODS: qRT-PCR analysis was conducted to examine the LINC00200 expression level in both GC tissues and cell lines. Functional assays were carried out to detect the effect of LINC00200 on GC cell proliferation, invasion and migration. The interaction between LINC00200 and miR-143-3p was confirmed by luciferase reporter assays. Rescue assays were performed to confirm the influence of LINC00200-miR-143-3p-SERPINE1 axis on GC development. RESULTS: LINC00200 was found to be upregulated in GC tissues and cell lines. Moreover, knockdown of LINC00200 suppressed GC cell proliferation, invasion and migration in vitro and inhibited tumorigenesis in mouse xenografts. Finally, mechanism research indicated that LINC00200 functioned as a ceRNA to sponge for miR-143-3p, thus leading to the disinhibition of its target gene SERPINE1. CONCLUSIONS: LINC00200 is significantly overexpressed in GC and accelerates GC progression through regulating miR-143-3p/SERPINE1 axis. Our results may provide a potential diagnostic biomarker and therapeutic target for the management of GC patients.

Serum microRNA expression profiling revealing potential diagnostic biomarkers for lung adenocarcinoma.

BACKGROUND: Recent studies have demonstrated that microRNAs (miRNAs) in the blood circulation can serve as promising diagnostic markers for cancers. This four-stage study aimed at finding serum miRNAs as potential biomarkers for lung adenocarcinoma (LA) diagnosis. METHODS: The study was carried out between 2016 and 2017. The Exiqon miRNA qPCR panel (3 LA vs. 1 normal control [NC] pooled serum samples) was used for initial screening to acquire miRNA profiles. Thirty-five dysregulated miRNAs were further evaluated in the training (24 LA vs. 24 NCs) and testing stages (110 LA vs. 110 NCs) using quantitative real-time polymerase chain reaction assays. RESULTS: Four serum miRNAs (miR-133a-3p, miR-584-5p, miR-10b-5p, and miR-221-3p) were significantly overexpressed in LA patients compared with NCs. The diagnostic value of the four-miRNA panel was validated by an external cohort (36 LA vs. 36 NCs). The areas under the receiver operating characteristic curve of the four-miRNA panel in the training, testing, and external validation stages were 0.734, 0.803, and 0.894 respectively. Meanwhile, the expression level of miR-221-3p was much higher in LA tumor samples than that in the adjacent normal tissues (19 LA vs. 19 NCs). The expression level of miR-10b-5p was also elevated in the serum-derived exosomes samples (18 LA vs. 18 NCs). The expression of miR-133a-3p, miR-584-5p, and miR-10b-5p was significantly elevated in LA patients with epidermal growth factor receptor mutation compared with NCs. CONCLUSION: The study established a four-miRNA signature in serum that could improve the diagnostic capability of LA.

Thioredoxin domain-containing protein 9 (TXNDC9) contributes to oxaliplatin resistance through regulation of autophagy-apoptosis in colorectal adenocarcinoma.

Colorectal cancer (CRC) is the third most commonly malignancy worldwide. The incidence of CRC is on the rise and leads to indisputable society burden due to the high cost of cancer treatments. Resistance to oxaliplatin-chemotherapy is the major cause for treatment failure and CRC-related death. In this study, we anticipated that TXNDC9 might demonstrate a protective role in oxaliplatin-resistant CRC cells. TXNDC9 was found significantly upregulated when treated with oxaliplatin. Manipulation of TXNDC9 expression largely affected the oxaliplatin-induced cell death. Moreover, TXNDC9 regulates autophagy and apoptosis in response to oxaliplatin treatment in HT29 cells via the Nrf2 pathway. Taken together, our findings explore the biological role of TXNDC9 in oxaliplatin resistance in CRC cells and may identify a novel therapeutic target to counteract drug resistance to oxaliplatin in CRC.

Circulating Epstein-Barr virus microRNA profile reveals novel biomarker for nasopharyngeal carcinoma diagnosis.

Nasopharyngeal carcinoma (NPC), a tumor quite prevalent in Asia, is closely associated with Epstein-Barr virus (EBV) infection status. Many NPC patients are not able to be treated in time when being diagnosed at an advanced stage. EBV-encoded microRNAs are reliable sources of biomarkers for NPC diagnosis. In this study, we conducted circulating EBV microRNAs profiling by quantitative reverse transcription polymerase chain reaction (qRT-PCR) among plasma samples of 159 NPC patients versus 145 normal controls (NCs) and serum samples of 60 NPC patients versus 60 NCs. Among the 44 mature EBV-encoded miRNAs, only miR-BART19-3p in plasma was proved to be significantly up-regulated in NPC patients (P< 0.05; fold change (FC) > 2.0). The area under the receiver operating characteristic curve (AUC) for the signature to discriminate NPC patients from NCs was 0.848 with the sensitivity and specificity being 71.7% and 72.3%, respectively. The identified biomarker was analyzed in tissue specimens (44 NPC VS. 32 NCs) and proved to be consistently up-regulated in NPC tumor tissues. Bioinformatics analysis was further conducted to predict the potential targets of miR-BART-19-3p, which provided some hints to its close relationship with NPC development. In conclusion, we identified a novel biomarker - plasma miR-BART19-3p for the detection of NPC.

Ternary cancer comprising prostatic cancer, esophageal cancer, and gastric cardia cancer: a case report and literature review.

A 61-year-old male patient was admitted to our hospital with frequent urination, urgency, and increased nocturia for more than 3 months, and the symptoms were aggravated for 1 week. Prostate biopsy revealed prostatic adenocarcinoma. After 5 months, the patient developed dysphagia and gastroscopy showed a middle and lower esophageal cancer (squamous cell carcinoma). 12 months later, he returned to the hospital because of dysphagia. He was examined by gastroscopy which showed the cardia to have low-grade adenocarcinoma. The patient was given Casodex + Zoladex endocrine therapy, zoledronic acid inhibiting bone destruction, concurrent chemoradiotherapy, capecitabinen tablets at a dose of 1000 mg bid, 3 cycles of intravenous paclitaxel at 180 mg/d1 plus cisplatin 60 mg/d1-2, 4 cycles of intravenous paclitaxel at 150 mg/d1 plus cisplatin at 60 mg/d1 as systemic chemotherapy. The curative effect is was considerable after treatment, and the patient's condition was stable. Since the onset of the disease in March 2018, the patient's condition had not progressed significantly for 27 months. The diagnosis and treatment of this patient with ternary cancer in the hospital improved the clinician's understanding of multiple primary cancers. Multidisciplinary treatment improved the patient's prognosis and quality of life. We reviewed similar case reports and retrospective studies of multiple primary cancers and found that there is no specific treatment for multiple primary cancers, but a corresponding treatment program can be formulated for each tumor to control progression while screening for possible other primary tumors.

PD-L1 for gallbladder cancer: case report.

The clinical outcome of the advanced biliary tract cancer (BTC) is unfavorable, and the mortality rate is high. With local advance and metastasis, the median survival time is less than 1 year. But this patient survived 14 months with no signs of progress under treatment in our hospital. And the patient situation is stable recently. This case report can provide a treatment template for clinicians. This patient was appeared dull pain in the upper abdomen, occasionally poor defaecating. After a series of medical tests, the patient was diagnosed with advanced gallbladder cancer (GBC). This patient received chemotherapy (oxaliplatin 220 mg d1 + capecitabine 1,500 mg bid d1-14; capecitabine 1,500 mg bid d1-14; gemcitabine 1.4 g d1, 8 + capecitabine 1,500 mg bid d1-14) combined with immunotherapy (pembrolizumab 200 mg). The patient is still alive.. And there were no signs of progress. The researches on the treatment of GBC are rare, and only standard first-line treatment, lack of second-line treatment of GBC. This patient of advanced GBC received standard first-line treatment (oxaliplatin 220 mg d1 + capecitabine 1,500 mg bid d1-14; capecitabine 1,500 mg bid d1-14; gemcitabine 1.4 g d1, 8 + capecitabine 1,500 mg bid d1-14) combined with immunotherapy (pembrolizumab 200 mg), the effect is fine and is expected to contribute to the treatment of BTC.

MicroRNA expression profiling analysis in serum for nasopharyngeal carcinoma diagnosis.

BACKGROUND: Circulating microRNAs have become reliable sources of non-invasive biomarkers for cancer diagnosis. miRNA expression analysis in blood circulation for the identification of novel signatures might assist the early detection of nasopharyngeal carcinoma (NPC) patients. METHODS: In the screening stage, the Exiqon miRNA qPCR panel was applied for the selection of candidate miRNAs. Serum samples taken from 208 NPC patients and 238 healthy donors (as normal controls (NCs)) were assigned to into the following three stages (training (30 NPC VS. 30 NCs), testing (138 NPC VS. 166 NCs) and external validation stage (40 NPC VS. 42 NCs)) for further confirmation of differently expressed miRNAs using qRT-PCR. The identified miRNA signatures were further explored in tissue specimens (48 NPC VS. 32 NCs) and serum-derived exosomes samples (32 NPC VS. 32 NCs). RESULTS: Five miRNAs in serum including let-7b-5p, miR-140-3p, miR-192-5p, miR-223-3p and miR-24-3p were found to be significantly up-regulated in NPC patients compared to NCs. The five identified miRNAs were further combined into one panel and the areas under the receiver operating characteristic curve (AUCs) for three independent stages were 0.910 (training), 0.916 (testing) and 0.968 (external validation), respectively. miR-192-5p and miR-24-3p were consistently up-regulated in NPC tissues while let-7b-5p and miR-140-3p were conversely down-regulated. In serum-derived exosomes samples, no expression difference was observed between NPC patients and NCs. CONCLUSION: A five-miRNA signature was identified in serum to be potential biomarkers for NPC detection.

MicroRNA-181a Inhibits Activated B-Cell-Like Diffuse Large B-Cell Lymphoma Progression by Repressing CARD11.

We investigated the role of miR-181a in diffuse large B-cell lymphoma (DLBCL) and its potential target genes. miR-181a levels were lower in activated B-cell- (ABC-) like DLBCL cells than that in germinal center B-cell- (GCB-) like DLBCL cells. Overexpression of miR-181a in ABC-like DLBCL cell lines (OCI-LY10 and U2932) resulted in G0/G1 cell cycle arrest, increased apoptosis, and decreased invasiveness. miRNA target prediction programs (miRanda, TargetScan, and miRDB) identified caspase recruitment domain-containing protein 11 (CARD11) as a putative miR-181a target. CARD11 mRNA and protein levels were higher in the ABC-like DLBCL than that in GCB-like DLBCL. Moreover, CARD11 mRNA and protein levels were downregulated in the OCI-LY10 and U2932 cell lines overexpressing miR-181a. Dual luciferase reporter assays confirmed the miR-181a binding site in the CARD11 3'UTR region. OCI-LY10 and U2932 cells transfected with a CARD11 expression vector encoding miR-181a with a mutated binding site showed higher CARD11 protein levels, cell viability, G2/M phase cells, and invasiveness compared to those transfected with a wild-type CARD11 expression vector. Nude mice xenografted with OCI-LY10 cells with overexpressed wild-type miR-181a generated smaller tumors compared to those with overexpressed mutated binding site of CARD11 3'UTR and miR-181a. These results indicate that miR-181a inhibits ABC-like DLBCL by repressing CARD11.

The Value of Plasma-Based MicroRNAs as Diagnostic Biomarkers for Ovarian Cancer.

BACKGROUND: Ovarian cancer (OC) is one of the most threatening diseases among women in the world. Plasma microRNAs (miRNAs) may serve as promising diagnostic biomarkers for patients with OC. MATERIALS AND METHODS: Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based on Exiqon panel, we identified 27 differentially expressed miRNAs from 2 OC pool samples and 1 normal control (NC) pool in the initial screening phase. Then we further validated the identified miRNAs through the training (32 OC vs. 34 NCs) and validation stages (69 OC vs. 66 NCs) using qRT-PCR. The expression levels of the miRNAs were also assessed in tissues and exosomes. RESULTS: Five plasma miRNAs (miR-205-5p, miR-145-5p, miR-10a-5p, miR-346 and miR-328-3p) were significantly overexpressed in OC in comparison with NCs. The areas under the receiver operating characteristic curve of the 5-miRNA panel were 0.788 for the training stage and 0.763 for the validation stage. The level of miR-205-5p has significantly different expression in patients with well-moderate histological grade compared with those with a poor grade (P = 0.012). The expression levels of the 5 miRNAs were also significantly upregulated in the exosomes of OC plasma samples (32 OC vs. 32 NCs). However, the expression of the 4 miRNAs (miR-145-5p, miR-10a-5p, miR-346 and miR-328-3p) was significantly lower in tumor samples than in normal tissues (22 OC vs. 22 NCs). CONCLUSIONS: The 5 plasma miRNAs may be noninvasive diagnostic biomarkers of OC. The plasma miR-205-5p level may reflect the change trend of the histological grade of OC patients.

Hsa_circ_0009361 acts as the sponge of miR-582 to suppress colorectal cancer progression by regulating APC2 expression.

Circular RNA (circRNA) plays an important role in the development of human malignant tumors. Recently, an increasing number of circRNAs have been identified and investigated in various tumors. However, the expression pattern and biological function of circRNAs in colorectal cancer (CRC) still remain largely unexplored. In the present study, hsa_circ_0009361 was significantly down-regulated in CRC tissues and cells. Low expression level of hsa_circ_0009361 promoted the proliferation, epithelial-mesenchymal transition (EMT), migration, and invasion of CRC cells. Hsa_circ_0009361 was identified as the sponge of miR-582 by fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and luciferase reporter assays. Overexpression of hsa_circ_0009361 up-regulated the expression of adenomatous polyposis coli 2 (APC2) and inhibited the activity of the Wnt/ß-catenin pathway by competitively combining with miR-582. Exogenous miR-582 and APC2 interventions could reverse the multiple biological functions mediated by hsa_circ_0009361 in CRC cells. In vivo experiments also confirmed that hsa_circ_0009361 inhibited the growth and metastasis of CRC. Hsa_circ_0009361 acted as a tumor suppressive sponge of miR-582, which could up-regulate the expression of APC2, inhibit the Wnt/ß-catenin signaling, and suppress the growth and metastasis of CRC. Collectively, the hsa_circ_0009361/miR-582/APC2 network could be employed as a potential therapeutic target for CRC patients.

Serum-plasma matched metabolomics for comprehensive characterization of benign thyroid nodule and papillary thyroid carcinoma.

Metabolomics offers a noninvasive methodology to identify metabolic markers for pathogenesis and diagnosis of diseases. This work aimed to characterize circulating metabolic signatures of benign thyroid nodule (BTN) and papillary thyroid carcinoma (PTC) via serum-plasma matched metabolomics. A cohort of 1,540 serum-plasma matched samples and 114 tissues were obtained from healthy volunteers, BTN and PTC patients enrolled from 6 independent centers. Untargeted metabolomics was determined by liquid chromatography-quadrupole time-of-flight mass spectrometric and multivariate statistical analyses. The use of serum-plasma matched samples afforded a broad-scope detection of 1,570 metabolic features. Metabolic phenotypes revealed significant pattern differences for healthy versus BTN and healthy versus PTC. Perturbed metabolic pathways related mainly to amino acid and lipid metabolism. It is worth noting that, BTN and PTC showed no significant differences but rather overlap in circulating metabolic signatures, and this observation was replicated in all study centers. For differential diagnosis of healthy versus thyroid nodules (BTN + PTC), a panel of 6 metabolic markers, namely myo-inositol, α-N-phenylacetyl-L-glutamine, proline betaine, L-glutamic acid, LysoPC(18:0) and LysoPC(18:1) provided area under the curve of 97.68% in the discovery phase and predictive accuracies of 84.78-98.18% in the 4 validation centers. Taken together, serum-plasma matched metabolomics showed significant differences in circulating metabolites for healthy versus nodules but not for BTN versus PTC. Our results highlight the true metabolic nature of thyroid nodules, and potentially decrease overtreatment that exposes patients to unnecessary risks.