A Preliminary Study on the Relationship Between High-Resolution Computed Tomography and Pulmonary Function in People at Risk of Developing Chronic Obstructive Pulmonary Disease.

Objectives: Patients with chronic obstructive pulmonary disease (COPD) have high morbidity and mortality, the opportunity to carry out a thoracic high-resolution CT (HRCT) scan may increase the possibility to identify the group at risk of disease. The aim of our study was to explore the differences in HRCT emphysema parameters, air trapping parameters, and lung density parameters between high and low-risk patients of COPD and evaluate their correlation with pulmonary function parameters. Methods: In this retrospective, single-center cohort study, we enrolled outpatients from the Physical Examination Center and Respiratory Medicine of The First Affiliated Hospital of Wenzhou Medical University. The patients who were ≥ 40 years-old, had chronic cough or sputum production, and/or had exposure to risk factors for the disease and had not reached the diagnostic criteria is considered people at risk of COPD. They were divided into low-risk group and high-risk group according to FEV1/FVC ≥ 80% and 80%>FEV1/FVC ≥ 70%. Data on clinical characteristics, clinical symptom score, pulmonary function, and HRCT were recorded. Results: 72 COPD high-risk patients and 86 COPD low-risk patients were enrolled in the study, and the air trapping index of left, right, and bilateral lungs of the high-risk group were higher than those of the low-risk group. However, the result of mean expiratory lung density was opposite. The emphysema index of left, right, and bilateral lungs were negatively correlated with FEV1/FVC (correlation coefficients were -0.33, -0.22, -0.26). Consistently, the air trapping index of left and right lungs and bilateral lungs were negatively correlated with FEV1/FVC (correlation coefficients were -0.33, -0.23, -0.28). Additionally, the mean expiratory lung density of left and right lungs and bilateral lungs were positively correlated with FEV1/FVC (correlation coefficients were 0.31, 0.25, 0.29). Conclusion: The emphysema index, air trapping index and the mean expiratory lung density shows significantly positive correlation with FEV1/FVC which can be used to assess the pulmonary function status of people at risk of COPD and provide a useful supplement for the early and comprehensive assessment of the disease.

Titin Mutation Is Associated With Tumor Mutation Burden and Promotes Antitumor Immunity in Lung Squamous Cell Carcinoma.

Lung squamous cell carcinoma (LUSC) is a leading cause of mobidity and mortality worldwide. Recently, there was a shift in the treatment pattern of immune therapy in LUSC patients; merely a small number of patients with non-small cell lung cancer (NSCLC) at advanced stages respond well to immune checkpoint blockade (ICB) therapy, and tumor mutation burden (TMB) is a valuable independent indicator of response to immune therapy. However, specific gene mutations and their relationship with TMB and tumor-infiltrating immunocytes in LUSC are still unclear. In the present paper, our team analyzed the somatically mutated genes from the ICGC (International Cancer Genome Consortium) and TCGA (The Cancer Genome Atlas) datasets and discovered that 15 frequent gene mutations occurred in both cohorts, including ZFHX4, MUC16, FLG, TP53, LRP1B, TTN, SYNE1, RYR2, CSMD3, USH2A, MUC17, DNAH5, FAM135B, COL11A1, and RYR3. Interestingly, only mutated TTN was related to higher TMB and prognostic outcomes among the 15 mutated genes. Moreover, according to the CIBERSORT algorithm, we revealed that TTN mutation enhanced the antitumor immune response. In conclusion, TTN may have important clinical implications for relevant immune therapy of lung squamous carcinoma.

A Nomogram Integrating Ferroptosis- and Immune-Related Biomarkers for Prediction of Overall Survival in Lung Adenocarcinoma.

Ferroptosis plays a dual role in cancer, which is known to be affected to antitumor immune responses. However, the association between ferroptosis and antitumor immune responses is uncertain in lung adenocarcinoma (LUAD). In this work, 38 ferroptosis-related genes (FRGs) and 429 immune-related genes (IRGs) were identified as being differentially expressed between tumor and normal samples. Two risk score formulas consisting of seven FRGs and four IRGs, respectively, were developed by Lasso-penalized Cox regression and verified in the GSE13213 dataset. The CIBERSORT algorithm was used to estimate the relative abundance of immune cells in tumors. The correlation between FRGs and immune cells was evaluated using the TIMER database. The results indicated that the development of ferroptosis was synergistic with that of anti-tumor immunity in LUAD. The concordance index and calibration curves showed that the performance of a nomogram that combines clinical staging and risk scores is superior to that of models using a single prognostic factor. In conclusion, ferroptosis might be synergistic with anti-tumor immunity in LUAD. The combined nomogram could reliably predict the probability of overall survival of LUAD patients. These findings may be useful for future investigation of prognostic value and therapeutic potential related to ferroptosis and tumor immunity in LUAD.

Wogonoside inhibits tumor growth and metastasis in endometrial cancer via ER stress-Hippo signaling axis.

Wogonoside, a bioactive flavonoid component derived from Scutellaria baicalensis Georgi, has been reported to inhibit tumor growth in mice bearing various types of cancer cells such as breast cancer, lung cancer, and leukemia cells. However, whether wogonoside could inhibit tumor growth of endometrial cancer has not been elucidated. In this study, we explored the function of wogonoside on tumor growth and the underlying mechanism on endometrial cancer. Firstly, we investigated the effect of wogonoside on endometrial cancer cells and found that wogonoside could significantly decrease cell proliferation and metastasis. Mechanistically, wogonoside could aggravate the extent of ER stress and upregulate the phosphorylation level of Mammalian Ste20-like kinase 1, leading to the activation of the Hippo signaling pathway. Taken together, in vitro and in vivo data demonstrated that wogonoside could be a potent inducer of ER stress and could be further developed into a promising therapy for endometrial cancer.