ESE1/AGR2 axis antagonizes TGF-ß-induced epithelial-mesenchymal transition in low-grade pancreatic cancer.

Epithelium-specific ETS transcription factor 1 (ESE1) has been implicated in epithelial homeostasis, inflammation, as well as tumorigenesis, and cancer progression. However, numerous studies have reported contradictory roles-as an oncogene or a tumor suppressor of ESE1 in different cancers, and its function in the development and progression of pancreatic ductal adenocarcinoma (PDAC) has remained largely unexplored. Herein, we report that ESE1 was found upregulated in primary PDAC compared to normal pancreatic tissue, but high expression of ESE1 correlated to better relapse-free survival in patients with PDAC. Interestingly, ESE1 was found to exhibit dual roles in regulation of malignant properties of PDAC cells in that its overexpression promoted cell proliferation, whereas its downregulation enhanced epithelial-mesenchymal transition (EMT) phenotype. In the context of TGF-ß-induced EMT, ESE1 is markedly downregulated at post-transcriptional level, and reconstituted ESE1 expression partially reversed TGF-ß-induced EMT marker expression. Furthermore, we identify AGR2 as a novel transcriptional target of ESE1 that participates in TGF-ß-induced EMT in PDAC. Collectively, our findings reveal an ESE1/AGR2 axis that interacts with TGF-ß signaling to modulate EMT phenotype in PDAC.

Supplementary benefits of CT-guided transthoracic lung aspiration biopsy for core needle biopsy.

Objective: This study aimed to investigate the diagnostic efficacy of computed tomography (CT)-guided transthoracic lung core needle biopsy combined with aspiration biopsy and the clinical value of this combined routine microbial detection. Materials and methods: We retrospectively collected the electronic medical records, CT images, pathology, and other data of 1085 patients with sequential core needle biopsy and aspiration biopsy of the same lung lesion under CT guidance in the First Affiliated Hospital of Wenzhou Medical University from January 2016 to January 2021. GenXpert MTB/RIF detection and BD BACTEC™ Mycobacterium/fungus culture were applied to identifying the microbiological results of these patients. We then compared the positive diagnostic rate, false negative rate, and diagnostic sensitivity rate of three methods including core needle biopsy alone, aspiration biopsy alone, and both core needle biopsy and aspiration biopsy. Results: The pathological results of cutting histopathology and aspiration of cell wax were examined for 1085 patients. The diagnostic rates of cutting and aspiration pathology were 90.1% (978/1085) and 86.3% (937/1085), respectively, with no significant difference (P > 0.05). Considering both cutting and aspiration pathologies, the diagnostic rate was significantly improved, up to 98% (1063/1085) (P < 0.001). A total of 803 malignant lesions were finally diagnosed (803/1085, 74.0%). The false negative rate by cutting pathology was 11.8% (95/803), which was significantly lower than that by aspiration biopsy [31.1% (250/803), P < 0.001]. Compared with core needle biopsy alone, the false negative rate of malignant lesions decreased to 5.6% (45/803) (P < 0.05). Next, the aspirates of the malignant lesions highly suspected of corresponding infection were cultured. The results showed that 16 cases (3.1%, 16/511) were infected with Mycobacterium tuberculosis complex, Aspergillus niger, and Acinetobacter baumannii, which required clinical treatment. 803 malignant tumors were excluded and 282 cases of benign lesions were diagnosed, including 232 cases of infectious lesions (82.3%, 232/282). The diagnostic rate of Mycobacterium/fungus culture for infectious lesions by aspiration biopsy (47.4%) was significantly higher than that by lung core needle biopsy (22.8%; P < 0.001). The diagnostic rate of aspiration biopsy combined with core needle biopsy was 56% (130/232). The parallel diagnostic rate of aspirated biopsy for GenXpert detection and Mycobacterium/fungal culture combined with core needle biopsy was 64.7% (150/232), which was significantly higher than that of lung core needle biopsy alone (P < 0.001). Finally, pulmonary tuberculosis was diagnosed in 90 cases (38.8%) of infectious lesions. Compared with the sensitivity of core needle biopsy to detect tuberculosis (27.8%, 25/90), the sensitivity of aspirating biopsy for GenXpert detection and Mycobacterium/fungal culture was significantly higher, at 70% (63/90) and 56.7% (51/90), respectively. Although there was no significant difference in the sensitivity of aspirated biopsy for GenXpert and Mycobacterium/fungal culture to detect pulmonary tuberculosis, the sensitivity was significantly increased to 83.3% (P < 0.05) when the two tests were combined. Moreover, when aspirated biopsies were combined with GenXpert detection, Mycobacterium/fungus culture, and core needle biopsy, the sensitivity was as high as 90% (81/90). Conclusion: CT-guided lung aspiration biopsy has a significant supplementary effect on core needle biopsies, which is indispensable in clinical application. Additionally, the combination of aspiration biopsy and core needle biopsy can significantly improve the diagnostic rate of benign and malignant lesions. Aspiration biopsy showed that pulmonary malignant lesions are complicated with pulmonary tuberculosis, aspergillus, and other infections. Finally, the diagnostic ability of lung puncture core needle biopsy and aspiration biopsy combined with routine microbial detection under CT positioning in the diagnosis of pulmonary infectious diseases was significantly improved.

NALP3 orchestrates cellular bioenergetics to facilitate non-small cell lung cancer cell growth.

AIMS: Previous work has reported the closely correlation between inflammation and carcinogenesis, while the role of NALP3, the key component of inflammasome activation in NSCLC remains elusive. This study was to unravel the mechanism of NALP3 on modulating NSCLC cancer cell growth. METHODS: IHC and immuno-blot were performed to analyze expression of NALP3 and indicated molecules. CCK-8 and xenograft nude mice assay were used to evaluate cell growth in vitro and in vivo. Bioenergetics assay was performed to measure OXPHOS and aerobic glycolysis. siRNA and shRNA were constructed to knockdown endogenous NALP3 and DNMT1. Co-immunoprecipitation was applied to confirm the interaction between NALP3 and DMAP1. BioProfile FLEX analyzer and Lactate Reagent Kit were used to measure relative level glucose uptake and lactate production. KEY FINDINGS: We reported NALP3 were up-regulated in NSCLC tumor tissues. NALP3 depletion suppressed cancer cell growth in vitro and in vivo. Moreover, data showed depletion of NALP3 promoted cell bioenergetics switch from aerobic glycolysis to OXPHOS. Additionally, we found NALP3 interacted with DMAP1 and alteration of NALP3 increased DNMT1 level. Subsequently, we clarified depletion of DNMT1 significantly suppressed NSCLC cell growth and orchestrated cellular metabolism which was similar to the effects of NALP3 knockdown. Finally, our data showed high NALP3 was associated with poor outcomes, and correlated with TNM stage and differentiation. SIGNIFICANCE: Current study elucidated NALP3 could promote metabolic reprogramming to regulate NSCLC cell growth and suggested that NALP3 may be considered as a novel biomarker and therapeutic target for NSCLC patients.

Standardized transbronchial needle aspiration procedure for intrathoracic lymph node staging of non-small cell lung cancer.

BACKGROUND: Thoracic lymph node (LN) metastasis is the determining factor for NSCLC staging. However, enlargement in thoracic LNs, which can be detected by chest computed tomography (CT), may not be adequate for NSCLC staging. This study aimed to investigate the effectiveness of a new transbronchial needle aspiration (TBNA) procedure to improve the sensitivity and accuracy of lung cancer diagnosis and staging. METHODS: A standardized TBNA procedure was performed on enlarged and non-enlarged LNs in the order of N3 to N1 station according to Wang's LN map. The status of LN metastasis determined by the standardized TBNA procedure was compared with the results from CT scan. RESULTS: The TBNA biopsy revealed that 21.43% of non-enlarged LNs were malignant. Compared with chest CT, the standardized TBNA procedure improved the accuracy of LN metastasis staging and discovered skip LN metastasis. CONCLUSIONS: The standardized TBNA procedure of this study may be recommended to be used as a routine TBNA procedure, in which LNs should be biopsied in the order of N3 to N1 station and both enlarged and non-enlarged LNs should be included to improve the accuracy of lung cancer staging.