Detection of PD­L1 expression and epithelial­mesenchymal transition of circulating tumor cells in non­small cell lung cancer.

The present study aimed to assess the roles of peripheral circulating tumor cell (CTC) count, CTC subtypes and programmed death ligand 1 (PD-L1) expression in the clinical staging and prognosis of patients with non-small cell lung cancer (NSCLC). A total of 100 patients with NSCLC with available tumor tissues were enrolled in the present study, and 7.5 ml peripheral blood was collected. Patients were divided into PD-L1-positive and PD-L1-negative groups according to PD-L1 immunohistochemical staining. Peripheral blood samples from both groups were analyzed to determine the CTC count, epithelial-type CTCs (E-CTCs), mesenchymal-type CTCs (M-CTCs) and PD-L1 expression. Clinical data were collected, and patients were followed up for a maximum of 36 months, with patient death as the endpoint event. Patients with PD-L1-positive tumors had a worse prognosis compared with those with PD-L1-negative tumors (P=0.045). The PD-L1-positive group exhibited significantly higher numbers of CTCs and M-CTCs compared with the PD-L1-negative group (P≤0.05). However, the number of E-CTCs did not differ significantly between the two groups (P>0.05). PD-L1-positive patients with higher CTC and M-CTC counts had relatively poorer prognoses (P≤0.05), while the number of E-CTCs had no significant effect on prognosis (P>0.05). Compared with the early-stage NSCLC group, the late-stage NSCLC group exhibited a significant increase in the CTC count (P≤0.05), while E-CTC and M-CTC counts did not significantly differ between the two groups (P>0.05). The PD-L1-positive group exhibited a significant increase in the number of PD-L1+ CTCs and PD-L1+ M-CTCs compared with the PD-L1-negative group (P≤0.05), while PD-L1+ E-CTC counts did not differ significantly between the two groups (P>0.05). The PD-L1-positive patients with a higher number of PD-L1+ CTCs and PD-L1+ M-CTCs had relatively poorer prognoses (P≤0.05), while the PD-L1+ E-CTC count had no significant effect on prognosis (P>0.05). Compared with the early-stage NSCLC group, the late-stage NSCLC group exhibited a significant increase in the number of PD-L1+ CTCs and PD-L1+ M-CTCs (P≤0.05), while PD-L1+ E-CTC counts did not significantly differ between the two groups (P>0.05). Based on univariate and multivariate analyses, the number of PD-L1+ M-CTCs was identified as an independent prognostic factor for NSCLC. In conclusion, the presence of CTCs in peripheral blood, particularly PD-L1+ M-CTC subtype, indicated poorer clinical staging and prognosis in patients with NSCLC. These findings suggested that CTCs, specifically the PD-L1+ M-CTC subtype, could serve as a monitoring indicator for the clinical staging and prognosis of patients with NSCLC.

Clinical and prognostic features associated with anti-Ro52 autoantibodies in connective tissue diseases patients with interstitial lung disease.

OBJECTIVES: To define the clinical and prognostic features associated with anti-Ro52 autoantibodies in patients with connective tissue diseases with interstitial lung disease (CTD-ILD). METHODS: A total of 238 patients with CTD-ILD were included in this single-centre retrospective cohort study. Patients with positive anti-Ro52 antibodies were selected as the study group, and those with negative anti-Ro52 antibodies were included in the control group. Clinical and follow-up data were analysed. RESULTS: Among 238 patients, 145 (60.92%) were positive for the anti-Ro52 antibody. These patients were more likely to have respiratory symptoms at baseline, with more organising pneumonia (OP) patterns and worse forced vital capacity (FVC). Follow-up data were obtained for ILD progression in 170 patients. Varying degrees of progression in pulmonary function (PF) or imaging were found in 48 patients (28.24%) with CTD-ILD. A dichotomous logistic analysis based on the presence or absence of progress showed no correlation with anti-Ro52 antibodies. During the follow-up of 170 patients, there were 35 deaths: 24 in the anti-Ro52 antibody positive group and 11 in the anti-Ro52 antibody negative group. Kaplan-Meier survival curves were used to describe the difference in survival between the two groups (mortality 17.14% vs. 12.5%, log-rank p=0.287). The multivariate logistic analysis showed that ILD progression was associated with older age, worse FVC and diffusion capacity for carbon monoxide at baseline, higher levels of C-reactive protein, serum ferritin, immunoglobulin G and lower absolute lymphocyte count. CONCLUSIONS: Anti-Ro52 antibodies may predict more severe lung damage in CTD-ILD; however, anti-Ro52 antibodies were not correlated with progression and death in patients with ILD.

Circular RNAs Hsa_circ_101555 and Hsa_circ_008068 as Diagnostic Biomarkers for Early-Stage Lung Adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is a life-threatening disease worldwide with a high mortality rate. The early diagnosis of LUAD is crucial for improving subsequent treatment and prognosis. However, biomarkers for early detection remain a clinical challenge in LUAD. Here, we aimed to develop circular RNAs (circRNAs) in circulating plasma from LUAD patients as valuable diagnostic biomarkers in LUAD. Methods: CircRNA expression was determined by circRNA microarray in three pairs of LUAD tumour tissues and patient-matched normal lung tissues. Hsa_circ_101555 and hsa_circ_008068 were selected as potential biomarkers in LUAD tissues and plasma by RT-PCR, respectively. The diagnostic value was analysed by the area under the curve (AUC) and the receiver operating characteristic (ROC) test. Results: Our results showed that 6261 circRNAs were upregulated and 7238 circRNAs were downregulated in LUAD tumour tissues compared with patient-matched normal lung tissues. Hsa_circ_101555 and hsa_circ_008068 were filtered as biomarkers for early-stage LUAD. Q-PCR results showed that hsa_circ_101555 and hsa_circ_008068 were significantly upregulated in both LUAD cancer tissues and circulating plasma. Hsa_circ_101555 and hsa_circ_008068 were positively associated with tumour differentiation, tumour size and CEA (P<0.05). The ROC analysis showed that hsa_circ_101555 and hsa_circ_008068 had a better diagnostic potential compared to the traditional biomarkers (CEA, SCC, CYFRA21-1) in the detection of early-stage LUAD. Conclusion: The circular RNAs hsa_circ_101555 and hsa_circ_008068 could serve as novel diagnostic biomarkers for early-stage LUAD.

Efficacy and Safety Profile of Montgomery T-Tube Implantation in Patients with Tracheal Stenosis.

Background: Tracheal stenosis is able to lead to airway obstruction. Objective: To evaluate the efficacy and safety profile of Montgomery T-tube implantation in patients with tracheal stenosis. Methods: Fifty-two patients with tracheal stenosis diagnosed between 2016 and 2019 were included in this retrospective cohort study. The patients were divided into observation group (n = 25 cases) and control group (n = 27). The therapeutic effect, arterial blood gas analysis, arterial oxygen partial pressure (PaO2), arterial carbon dioxide partial pressure (PaCO2), shortness of breath score, airway diameter change, dyspnea score, quality of life, and safety were compared between the two groups before and after treatment. Results: The therapeutic effect of the observation group gained better results than that of the control group (84.00% vs. 62.96%). One week after operation, the pH value, SaO2, PaCO2, shortness of breath score, airway diameter change, dyspnea score, life quality, and incidence of postoperative complications in the observation group exerted better results as compared to the control group. Conclusion: The implantation of Montgomery T-tube has effective function in terms of improving the symptoms of dyspnea and the life quality of patients with safety profile in patients harboring tracheal stenosis.

The Gene Expression Biomarkers for Chronic Obstructive Pulmonary Disease and Interstitial Lung Disease.

COPD (chronic obstructive pulmonary disease) and ILD (interstitial lung disease) are two common respiratory diseases. They share similar clinical traits but require different therapeutic treatments. Identifying the biomarkers that are differentially expressed between them will not only help the diagnosis of COPD and ILD, but also provide candidate drug targets that may facilitate the development of new treatment for COPD and ILD. Due to the irreversible complex pathological changes of COPD, there are very limited therapeutic options for COPD patients. In this study, we analyzed the gene expression profiles of two datasets: one training dataset that includes 144 COPD patients and 194 ILD patients, and one test dataset that includes 75 COPD patients and 61 ILD patients. Advanced feature selection methods, mRMR (minimal Redundancy Maximal Relevance) and incremental feature selection (IFS), were applied to identify the 38-gene biomarker. An SVM (support vector machine) classifier was built based on the 38-gene biomarker. Its accuracy, sensitivity, and specificity on training dataset evaluated by leave one out cross-validation were 0.905, 0.896, and 0.912, respectively. And on independent test dataset, the accuracy, sensitivity, and specificity on were as great as and were 0.904, 0.933, and 0.869, respectively. The biological function analysis of the 38 genes indicated that many of them can be potential treatment targets that may benefit COPD and ILD patients.

Long noncoding RNA UPAT promoted cell proliferation via increasing UHRF1 expression in non-small cell lung cancer.

Evidence indicates that long non-coding RNAs (lncRNAs) serve a critical role in the regulation of non-small cell lung cancer (NSCLC) progression. LncRNA Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) protein associated transcript (UPAT) has been identified to be overexpressed in a variety of types of cancer. The present study demonstrated that lncRNA UPAT expression was upregulated in NSCLC tissues and significantly associated with tumor size and Tumor-Node-Metastasis stage. Additionally, UPAT promoted NSCLC cell proliferation and G1-S phase transition in vitro. Furthermore, UPAT promoted NSCLC cell proliferation, partly via increasing UHRF1 expression and consequently epigenetically silencing RASSF1 and CDH13 transcription. In addition, the knockdown of UHRF1 partially decreased the promotion of cell growth and G1-S phase transition caused by UPAT overexpression. In conclusion, these data suggest that the lncRNA UPAT promotes the NSCLC cell proliferation and may be a potential therapeutic target of NSCLC.