Low Expression MCEMP1 Promoting Lung Adenocarcinoma Progression by and its Clinical Value.

BACKGROUND: Lung cancer is a highly prevalent tumor with a lack of biological markers that reflect its progression. Mast cell surface membrane protein 1 (MCEMP1, also known as C19ORF59) has not been reported in lung adenocarcinoma (LUAD). OBJECTIVE: We aimed to investigate the role of MCEMP1 in LUAD. METHODS: MCEMP1 expression in LUAD was analyzed using The Cancer Genome Atlas (TCGA) data, and conducted univariate and multivariate Cox regression analyses to evaluate the prognostic significance of MCEMP1 expression in TCGA. Tumor Immune Estimation Resource (TIMER) was used for examining the correlation between MCEMP1 expression and immune cell infiltration in LUAD. Furthermore, proliferation, migration, invasion, and colony-forming ability were investigated using LUAD cell lines. RESULTS: MCEMP1 had low expression in LUAD patient tissues and was correlated with lymph node metastasis, differentiation level, and tumor status. The Area under Curve (AUC) value of MCEMP1 for the Receiver Operating Characteristic (ROC) curve analysis was 0.984. The immune infiltration analysis revealed a correlation between MCEMP1 expression and the extent of macrophages and neutrophil infiltration in LUAD. Additionally, MCEMP1 has low expression in clinical samples, MCEMP1 overexpressed in LUAD cells substantially reduced cell growth, migration, and invasion of malignant cells. CONCLUSION: Low expression MCEMP1 promotes LUAD progression, which provides new insights and a potential biological target for future LUAD therapies.

A Prediction Model for Clinical Outcomes of COVID-19 Hospitalized Patients: Construction and Accuracy Assessment.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic spread rapidly with considerable morbidity nationwide since China's liberalization in December 2022. Our work has focused on identifying different predictive factors from the laboratory examination of critically ill patients, and forecasting the unfavorable outcome of critically ill patients with COVID-19 through a combined diagnosis of biological markers. METHODS: We conducted a retrospective study at the Department of First Affiliated Hospital of Wenzhou Medical University, China, from December 24, 2022, to January 10, 2023, where 434 critically ill patients who met the inclusion criteria were involved. Machine analysis was employed to search for the parameters with the highest predictive value to calculate COVID-19 mortality by exploiting 66 typical laboratory results. RESULTS: Combined diagnosis of serum albumin (ALB), lactate dehydrogenase (LDH), direct bilirubin (Dbil), ferritin, pulse oxygen saturation (SpO2), and neutrophil count (NEUT#) was evaluated, and the result with the highest predictive value (NEUT#) was selected as the predictor for COVID-19 mortality with a sensitivity of 89.2% and a specificity of 77.4%. CONCLUSIONS: The increased levels of LDH, Dbil, ferritin, and NEUT#, along with lowered ALB and SpO2 levels are the most decisive variables for forecasting the mortality for COVID-19 according to our machine-learning-based model. The combined diagnosis could be used to improve further diagnostic performance.

Long Noncoding RNA ZBED5-AS1 Facilitates Tumor Progression and Metastasis in Lung Adenocarcinoma via ZNF146/ATR/Chk1 Axis.

Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis, including lung adenocarcinoma (LUAD). However, the functional and regulatory mechanisms of lncRNAs in LUAD remain poorly understood. In this study, we investigated the role of lncRNA ZBED5-AS1 in LUAD. We found that ZBED5-AS1 was upregulated in LUAD specimens and overexpressed in LUAD cell lines. ZBED5-AS1 promoted LUAD cell proliferation, migration, and invasion in vitro and promoted LUAD cell growth in vivo. ZBED5-AS1 promoted ZNF146 expression, activating the ATR/Chk1 pathway and leading to LUAD progression. We observed that exosomes from LUAD cells have a higher expression of ZBED5-AS1 compared with exosomes from the normal cell line BEAS-2B. Coculture experiments with exosomes showed that ZBED5-AS1 expression was downregulated after coculture with Si-ZBED5-AS1 exosomes, and coculture with exosomes with low ZBED5-AS1 expression inhibited proliferation and invasion of LUAD cells. Our results indicate that ZBED5-AS1 functions as an oncogenic factor in LUAD cells by targeting the ZNF146/ATR/Chk1 axis.

Diagnostic value of pleural effusion Krebs von den Lungen-6 in malignant pleural effusion of patients with non-small cell lung cancer.

OBJECTIVE: The aim of this study was to investigate the diagnostic potential of Krebs von den Lungen-6 (KL-6) in differentiating between malignant pleural effusion (MPE) induced by non-small cell lung cancer (NSCLC) and benign pleural effusion (BPE). METHODS: We collected 143 pleural effusion samples from August 2018 to March 2021. The samples included 91 cases of MPE and 52 cases of BPE. The KL-6 and other indicators in pleural effusion were detected. RESULTS: The level of pleural effusion KL-6 (pKL-6) in the MPE group was significantly higher than in the BPE group (Mann-Whitney U = 442.500, P = .000). The area under the curve (AUC) of pKL-6/pleural effusion adenosine deaminase (pADA) + pleural effusion carcinoembryonic antigen (pCEA)/pADA (AUC = 0.992) in diagnosing MPE was higher than that of pKL-6 alone (AUC = 0.903), with a sensitivity of 93.26% and specificity of 100%. CONCLUSION: The measurement of pKL-6 can differentiate NSCLC-induced MPE from BPE. Furthermore, the combined detection of pKL-6/pADA and pCEA/pADA can significantly improve the diagnostic efficiency for distinguishing NSCLC-induced MPE.

STAMBPL1 promotes the progression of lung adenocarcinoma by inhibiting DHRS2 expression.

BACKGROUND: Lung cancer is responsible for the majority of cancer deaths in the world. We found a significant increase of STAMBPL1 expression in lung adenocarcinoma (LUAD) tissues and cells. However, its mechanism has not been clarified. METHODS: LUAD tissues and adjacent normal tissues were collected from 62 patients treated in the First Affiliated Hospital of Wenzhou Medical University from August 2018 to August 2021. In vivo, the clinical data and STAMBPL1 expression of 62 patients with LUAD were analyzed by qPCR. In vitro, cell experiments were carried out after STAMBPL1 knockdown in A549 and H1299 cells to determine cell growth, migration rate, evasiveness, colony-forming ability, and apoptosis. Gene sequencing was used to explore the expression of various genes in A549 and H1299 cells to verify that DHRS2 was up-regulated after STAMBPL1 knockdown; cell experiments further detected the role of the DHRS2 gene after DHRS2 overexpression in A549 and H1299 cells. A rescue experiment was conducted to certify that STAMBPL1 promotes NSCLC progression by regulating DHRS2 expression. RESULTS: After STAMBPL1 knockdown by siRNA. Migration, invasion, colony formation, and proliferation of siRNA groups were suppressed than those of NC groups in A549 and H1299 cells, while the cell apoptosis rate of siRNA groups increased significantly. By using gene-sequence analysis, we found that the expression level of the DHRS2 gene was up-regulated in STAMBPL1 siRNA groups, compared with STAMBPL1 NC (negative control) groups in A549 and H1299, which was verified by qPCR and WB. Further experiments showed that the DHRS2 OE group was suppressed in cell proliferation, migration, and invasion in the A549 and H1299 cell lines compared to the DHRS2 NC group, while DHRS2 OE group was significantly enhanced in the cell apoptosis in the A549 and H1299 cell lines. According to the rescue experiment, cell proliferation, migration, and invasion of the STAMBPL1 SI+DHRS2 SI group were enhanced compared with the STAMBPL1 SI+DHRS2 NC group in A549 and H1299 cells, while the STAMBPL1 SI+DHRS2 OE group were further decreased. CONCLUSIONS: The expression of STAMBPL1 mRNA is significantly up-regulated in LUAD, promoting the progression of LUAD by down-regulating the expression of DHRS2 and acting as a potential biomarker of LUAD.

LncRNA UCA1 promoted cisplatin resistance in lung adenocarcinoma with HO1 targets NRF2/HO1 pathway.

PURPOSE: Our previous experiments have demonstrated that lncRNA UCA1 (UCA1) promoted cisplatin resistance in lung adenocarcinoma (LUAD). This study aimed to explore the potential downstream target genes regulated by UCA1 and how this downstream gene promotes cisplatin resistance in LUAD. METHODS: Here, we measured the expression level of Heme oxygenase1 (HO1) in LUAD cell lines by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) based on UCA1 overexpression cell lines and UCA1 knockdown cell lines. HO1 was knocked down in the UCA1 overexpression cell line, and HO1 was overexpressed in the UCA1 knockdown cell line, and the half maximal inhibitory concentration (IC50) trends were observed by adding cisplatin containing a certain concentration gradient. Cell functional assays were performed to observe the changes in the biological behavior of HO1 after overexpression and knockdown, and the tumorigenic assay in nude mice was performed to verify the effect of UCA1 in regulating the growth and cisplatin resistance of HO1 on LUAD cells in vivo. RESULTS: The results showed that HO1 and UCA1 expression were both upregulated in LUAD tissues and LUAD cisplatin-resistant cell lines, and there was a significant positive correlation between the expression of HO1 and UCA1. In vitro experiments showed that HO1 overexpression could reverse the reduced sensitivity to cisplatin caused by UCA1 knockdown in A549/DDP cells, and HO1 knockdown could reduce cisplatin resistance in A549 UCA1 overexpressing cells. Tumorigenic assays in nude mice further confirmed the role of HO1 in the regulation of UCA1 by activating the NRF2/HO1 pathway against LUAD cisplatin resistance. CONCLUSION: Our findings suggested that UCA1 regulates HO1 targets the UCA1/NRF2-HO1 pathway to exert cisplatin resistance in LUAD.

Establishing a metastasis-related diagnosis and prognosis model for lung adenocarcinoma through CRISPR library and TCGA database.

PURPOSE: Existing biomarkers for diagnosing and predicting metastasis of lung adenocarcinoma (LUAD) may not meet the demands of clinical practice. Risk prediction models with multiple markers may provide better prognostic factors for accurate diagnosis and prediction of metastatic LUAD. METHODS: An animal model of LUAD metastasis was constructed using CRISPR technology, and genes related to LUAD metastasis were screened by mRNA sequencing of normal and metastatic tissues. The immune characteristics of different subtypes were analyzed, and differentially expressed genes were subjected to survival and Cox regression analyses to identify the specific genes involved in metastasis for constructing a prediction model. The biological function of RFLNA was verified by analyzing CCK-8, migration, invasion, and apoptosis in LUAD cell lines. RESULTS: We identified 108 differentially expressed genes related to metastasis and classified LUAD samples into two subtypes according to gene expression. Subsequently, a prediction model composed of eight metastasis-related genes (RHOBTB2, KIAA1524, CENPW, DEPDC1, RFLNA, COL7A1, MMP12, and HOXB9) was constructed. The areas under the curves of the logistic regression and neural network were 0.946 and 0.856, respectively. The model effectively classified patients into low- and high-risk groups. The low-risk group had a better prognosis in both the training and test cohorts, indicating that the prediction model had good diagnostic and predictive power. Upregulation of RFLNA successfully promoted cell proliferation, migration, invasion, and attenuated apoptosis, suggesting that RFLNA plays a role in promoting LUAD development and metastasis. CONCLUSION: The model has important diagnostic and prognostic value for metastatic LUAD and may be useful in clinical applications.

Differential expression and analysis of extrachromosomal circular DNAs as serum biomarkers in lung adenocarcinoma.

BACKGROUND: Extrachromosomal circular DNAs (eccDNAs) increase the number of proto-oncogenes by enhancing oncogene expression to promote tumorigenesis. However, there are limited reports on differential eccDNA expression and analysis in lung cancer, especially in lung adenocarcinoma (LAD). METHODS: Three LAD and three corresponding NT tissues samples were used for eccDNA next-generation sequencing analysis, and an additional 20 were used for quantitative PCR (qPCR) evaluations. We further performed qPCR amplification using serum samples from LAD patients and healthy medical examiners. RESULTS: eccDNAs from LAD samples were mainly 200-1000 bp in length. Gene annotation analysis revealed that most eccDNAs were derived from chromosomes 1 and 2. The top-ten increased and top-ten decreased eccDNAs in LAD tissues were CircD-ARPC1B, CircD-ARPC1A, CircD-FAM49B, CircD-SDK1, CircD-KCNG1, CircD-POLR2F, CircD-SS18L1, CircD-SLC16A3, CircD-CSNK1D, CircD-KCTD1, and CircD-TMIGD2, CircD-PDIA5, CircD-VAV2, CircD-GATAD2A, CircD-CAB39L, CircD-KHDC1, CircD-FOXN3, CircD-SULT2B1, CircD-DPP9, and CircD-CSNK1D. qPCR demonstrated that the expression of CircD-DZRN3 was higher in LAD tissues than in normal lung tissues, whereas CircD-LGR6 and CircD-UMODL1 expression levels were lower in LAD than in normal lung tissues. Furthermore, the serum CircD-PDZRN3 level increased, while CircD-LGR6 decreased in LAD. Receiver operating characteristic (ROC) analysis showed that area under curve (AUC) of serum CircD-PDZRN3 (0.991), CircD-LGR6 (0.916) was higher than that of serum carcinoembryonic antigen (CEA) (0.825), CY211 (cytokeratin 19 fragment) (0.842), SCCA(squamous cell carcinoma antigen) (0.857) for the diagnosis of LAD. CONCLUSIONS: Our study first showed that several eccDNAs were aberrantly expressed in LAD, among which CircD-PDZRN3 and CircD-LGR6 clearly distinguished LAD patients from healthy controls, indicating their potential as biomarkers.