The value of contrast-enhanced harmonic endoscopic ultrasound in differential diagnosis and evaluation of malignant risk of gastrointestinal stromal tumors (<50mm).

OBJECTIVES: Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) has been used in the differential diagnosis of benign and malignant tumors by visualization of tumor microcirculation and perfusion. However, its diagnostic role in submucosal tumors (SMTs), especially leiomyomas and gastric submucosal tumors (GISTs) was rarely studied. The aim of this study was to analyze the diagnostic role of CEH-EUS for SMTs (<50 mm) and the value of assessing the malignant potential of GISTs. MATERIALS AND METHODS: We retrospectively included patients with tumors <50 mm in diameter who underwent preoperative EUS and CEH-EUS examination and had pathologically confirmed as leiomyomas and GISTs. To analyze the imaging features of CEH-EUS with pathological diagnosis as the gold standard and evaluate its diagnostic value. RESULTS: This study included 10 cases of leiomyomas and 38 cases of GISTs. Under CEH-EUS detection, 86.9% of GISTs showed hyper-enhancement, 89.5% showed diffuse enhancement, 39.5% showed non-enhancing spots, and 97.4% showed obvious capsule enhancement. In contrast, the leiomyoma cases mostly showed hypo-enhancement (50.0%) or non-enhancement (30.0%) (p < 0.05). Then, the value of CEH-EUS in the differential diagnosis of benign and malignant tumors based on blood flow is significantly higher than that of B-EUS. Signal appearance time was significantly faster in the intermediate-high risk GISTs than in the very low-low risk group (5.1 s versus 15.5 s, p < 0.05), and the AUROC values predicted the risk at this time to be 0.903 (0.763-0.975). Heterogeneous perfusion and non-enhancing spots were also more common in the intermediate-high risk group. Univariate and multivariate analysis revealed that intratumoral irregularitie was an independent predictor of moderate to high risk (OR 3.99, 95%CI 1.04-90.95), with sensitivity, specificity and accuracy of 73.33%, 91.30% and 84.21%, respectively. CONCLUSIONS: Through this study, CEH-EUS has a good differential diagnostic ability for leiomyomas and GISTs, and has a high value in predicting the risk of GISTs.

Diagnostic value of new biliary biopsy cannulae for malignant bile duct strictures via endoscopic retrograde cholangiopancreatography pathway.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) plays a major role in the diagnosis of malignant biliary strictures. ERCP fluoroscopy-guided biliary biopsy is more sensitive than brushing, but it is more difficult to perform and less successful. Therefore, a new technique of biliary biopsy using a new biliary biopsy cannula via the ERCP route was developed in our center with the aim of improving the diagnosis rate of malignant biliary strictures. METHODS: This is a retrospective study that included 42 patients who underwent ERCP-guided biliary brushing and biliary biopsy for biliary strictures using a new biliary biopsy cannula in our department from January 2019 to May 2022. The final diagnosis was determined after brushing, biliary biopsy under the new biliary biopsy cannula or adequate follow-up. Diagnostic rates were calculated and analyzed for relevant factors. RESULTS: The satisfactory rates of pathological specimens of 42 patients who underwent bile duct biopsy with bile duct brush and new bile duct biopsy cannula were 57.14% and 95.24% respectively. Cholangiocarcinoma was diagnosed in 45.23% and 83.30% of the samples by biliary brush examination and biliary biopsy using the new biliary biopsy cannula, respectively (p < 0.001). CONCLUSIONS: The ERCP route using a new biliary biopsy cannula for biliary biopsy technique can improve pathology positivity and benefit ratio. It provides a new approach in the diagnosis of malignant stenosis in the bile duct.

RNA N6-methyladenosine reader IGF2BP3 promotes acute myeloid leukemia progression by controlling stabilization of EPOR mRNA.

Background: N6-methyladenosine (m6A) methylation epigenetically regulates normal hematopoiesis and plays a role in the pathogenesis of acute myeloid leukemia (AML). However, its potential value for prognosis remains elusive. Methods: Analysis of the datasets downloaded from The Cancer Genome Atlas and Genotype Tissue Expression databases revealed that the expression level of 20 regulators related to m6A RNA methylation differ between patients with AML and normal individuals. A prognostic risk model with three genes (YTHDF3, IGF2BP3, and HNRNPA2B1) was developed using univariate Cox regression and the least absolute shrinkage and selection operator Cox regression methods. Results: This established signature demonstrated good predictive efficacy with an area under the curve of 0.892 and 0.731 in the training cohort and the validation cohort, respectively. Patients with AML and an increased level of Insulin growth factor 2 mRNA binding protein 3 (IGF2BP3) expression exhibited a poor prognosis. IGF2BP3 knockdown significantly induced G0/G1 phase arrest and inhibited cell proliferation, apoptosis, and/or differentiation. Further, the JAK/STAT pathway may be involved in the regulation of EPOR expression by IGF2BP3-mediated m6A RNA methylation. Conclusion: These findings indicate that IGF2BP3 plays a carcinogenic role in AML, implying that it can predict patient survival and could be an effective strategy for AML therapy.

Aquaporin 1 is a prognostic marker and inhibits tumour progression through downregulation of Snail expression in intrahepatic cholangiocarcinoma.

BACKGROUND: Recently, some studies have suggested a link between AQP1 and cancer progression. AIMS: The aim of the present study was to investigate the influence of AQP1 on the clinicopathology and prognosis of intrahepatic cholangiocarcinoma (ICC) patients. METHODS: We retrospectively detected the expression of AQP1 protein in 307 patients with ICC who underwent partial hepatectomy. Western blot analysis was used to detect AQP1 protein levels in stable AQP1 overexpression and knockdown cell lines. The influence of AQP1 on the invasion and metastasis ability of ICC cells was assessed by wound-healing and Transwell assays in vitro as well as by a splenic liver metastasis model in vivo. RESULTS: Positive membranous AQP1 expression was identified in 34.2% (105/307) of the ICC specimens. Survival data revealed that positive AQP1 expression was significantly associated with favourable disease-free survival (DFS) and overall survival (OS) (p = 0.0290 and p = 0003, respectively). Moreover, high AQP1 expression inhibited the invasion and migration of ICC cells in vitro as well as inhibited liver metastasis in nude mice. Mechanistically, high AQP1 expression in ICC cells increased the levels of E-cadherin but decreased the levels of the Snail transcription factor. CONCLUSIONS: AQP1 expression is associated with a favourable prognosis in ICC patients. AQP1 inhibits ICC cell invasion, metastasis, and epithelial-mesenchymal transition (EMT) through downregulation of Snail expression.

MEG3 LncRNA from Exosomes Released from Cancer-Associated Fibroblasts Enhances Cisplatin Chemoresistance in SCLC via a MiR-15a-5p/CCNE1 Axis.

PURPOSE: Long non-coding RNAs (lncRNAs) may act as oncogenes in small-cell lung cancer (SCLC). Exosomes containing lncRNAs released from cancer-associated fibroblasts (CAF) accelerate tumorigenesis and confer chemoresistance. This study aimed to explore the action mechanism of the CAF-derived lncRNA maternally expressed gene 3 (MEG3) on cisplatin (DDP) chemoresistance and cell processes in SCLC. MATERIALS AND METHODS: Quantitative real-time PCR was conducted to determine the expression levels of MEG3, miR-15a-5p, and CCNE1. Cell viability and metastasis were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide and invasion assays, respectively. A xenograft tumor model was developed to confirm the effect of MEG3 overexpression on SCLC progression in vivo. Relationships between miR-15a-5p and MEG3/CCNE1 were predicted using StarBase software and validated by dual luciferase reporter assay. Western blotting was used to determine protein levels. A co-culture model was established to explore the effects of exosomes on MEG3 expression in SCLC cell lines. RESULTS: MEG3 was overexpressed in SCLC tissues and cells. MEG3 silencing significantly repressed cell viability and metastasis in SCLC. High expression of MEG3 was observed in CAF-derived conditioned medium (CM) and exosomes, and promoted chemoresistance and cancer progression. Additionally, MEG3 was found to serve as a sponge of miR-15a-5p to mediate CCNE1 expression. Overexpression of miR-15a-5p and knockout of CCNE1 reversed the effects of MEG3 overexpression on cell viability and metastasis. CONCLUSION: MEG3 lncRNA released from CAF-derived exosomes promotes DDP chemoresistance via regulation of a miR-15a-5p/CCNE1 axis. These findings may provide insight into SCLC therapy.

Correlation of IL-6 and JAK2/STAT3 signaling pathway with prognosis of nasopharyngeal carcinoma patients.

IL-6 is reported to be the main upstream activator, instead of the downstream target of JAK2/STAT3. This study is intended to explore the correlation of IL-6 and JAK2/STAT3 signaling pathway with clinicopathological features and prognosis in nasopharyngeal carcinoma (NPC). First, NPC tissues and normal nasopharyngeal epithelial tissues were obtained from 117 NPC patients. Next, we detected expression levels of IL-6 in serum and those of STAT3, p-STAT3, JAK2, p-JAK2 and CyclinD1 in tissues. A follow-up was conducted in all the patients and the survival was analyzed. To verify the correlation of IL-6 and JAK2/STAT3 pathway, CNE-1 and SUNE1 NPC cells were interpreted with IL-6 and JAK2/STAT3 signaling pathway inhibitor AG490 to detect cell viability, migration and invasion. We observed thatIL-6 increased in serum of NPC patients. The expressions of IL-6, STAT3, p-STAT3, JAK2, p-JAK2 and CyclinD1 in NPC tissues were higher and correlated with TNM stage and lymph node metastasis (LNM). Survival rates were reduced in patients with positive expressions of IL-6, STAT3, p-STAT3, JAK2, p-JAK2 and CyclinD1. LNM and positive expressions of IL-6 and p-STAT3 were risk factors for poor prognosis of NPC. Besides, recombinant human IL-6 promoted cell proliferation, invasion and migration while AG490 inhibited cell proliferation, invasion and migration in CNE-1 and SUNE1 NPC cells. The results demonstrated that increased IL-6 expression and the activated JAK2/STAT3 signaling pathway had effects on prognosis and reduced the survival time in NPC patients, which provide a potential target for the treatment of NPC.