Identification of a cancer-associated fibroblast classifier for predicting prognosis and therapeutic response in lung squamous cell carcinoma.

Reliable prognostic gene signatures for cancer-associated fibroblasts (CAFs) in lung squamous cell carcinoma (LUSC) are still lacking, and the underlying genetic principles remain unclear. Therefore, the 2 main aims of our study were to establish a reliable CAFs prognostic gene signature that can be used to stratify patients with LUSC and to identify promising potential targets for more effective and individualized therapies. Clinical information and mRNA expression were accessed of the cancer genome atlas-LUSC cohort (n = 501) and GSE157011 cohort (n = 484). CAFs abundance were quantified by the multi-estimated algorithms. Stromal CAF-related genes were identified by weighted gene co-expression network analysis. The least absolute shrinkage and selection operator Cox regression method was utilized to identify the most relevant CAFs candidates for predicting prognosis. Chemotherapy sensitivity scores were calculated using the "pRRophetic" package in R software, and the tumor immune dysfunction and exclusion algorithm was employed to evaluate immunotherapy response. Gene set enrichment analysis and the Search Tool for Interaction of Chemicals database were applied to clarify the molecular mechanisms. In this study, we identified 288 hub CAF-related candidate genes by weighted gene co-expression network analysis. Next, 34 potential prognostic CAFs candidate genes were identified by univariate Cox regression in the cancer genome atlas-LUSC cohort. We prioritized the top 8 CAFs prognostic genes (DCBLD1, SLC24A3, ILK, SMAD7, SERPINE1, SNX9, PDGFA, and KLF10) by a least absolute shrinkage and selection operator Cox regression model, and these genes were used to identify low- and high-risk subgroups for unfavorable survival. In silico drug screening identified 6 effective compounds for high-risk CAFs-related LUSC: TAK-715, GW 441756, OSU-03012, MP470, FH535, and KIN001-266. Additionally, search tool for interaction of chemicals database highlighted PI3K-Akt signaling as a potential target pathway for high-risk CAFs-related LUSC. Overall, our findings provide a molecular classifier for high-risk CAFs-related LUSC and suggest that treatment with PI3K-Akt signaling inhibitors could benefit these patients.

Dynamic change of COVID-19 lung infection evaluated using co-registration of serial chest CT images.

Purpose: To evaluate the volumetric change of COVID-19 lesions in the lung of patients receiving serial CT imaging for monitoring the evolution of the disease and the response to treatment. Materials and methods: A total of 48 patients, 28 males and 20 females, who were confirmed to have COVID-19 infection and received chest CT examination, were identified. The age range was 21-93 years old, with a mean of 54 ± 18 years. Of them, 33 patients received the first follow-up (F/U) scan, 29 patients received the second F/U scan, and 11 patients received the third F/U scan. The lesion region of interest (ROI) was manually outlined. A two-step registration method, first using the Affine alignment, followed by the non-rigid Demons algorithm, was developed to match the lung areas on the baseline and F/U images. The baseline lesion ROI was mapped to the F/U images using the obtained geometric transformation matrix, and the radiologist outlined the lesion ROI on F/U CT again. Results: The median (interquartile range) lesion volume (cm3) was 30.9 (83.1) at baseline CT exam, 18.3 (43.9) at first F/U, 7.6 (18.9) at second F/U, and 0.6 (19.1) at third F/U, which showed a significant trend of decrease with time. The two-step registration could significantly decrease the mean squared error (MSE) between baseline and F/U images with p < 0.001. The method could match the lung areas and the large vessels inside the lung. When using the mapped baseline ROIs as references, the second-look ROI drawing showed a significantly increased volume, p < 0.05, presumably due to the consideration of all the infected areas at baseline. Conclusion: The results suggest that the registration method can be applied to assist in the evaluation of longitudinal changes of COVID-19 lesions on chest CT.

Arc concave sign on thin-section computed tomography：A novel predictor for invasive pulmonary adenocarcinoma in pure ground-glass nodules.

OBJECTIVE: We aimed to investigate the risk factors of invasive pulmonary adenocarcinoma, especially to report and validate the use of our newly identified arc concave sign in predicting invasiveness of pure ground-glass nodules (pGGNs). METHODS: From January 2015 to August 2018, we retrospectively enrolled 302 patients with 306 pGGNs ≤ 20 mm pathologically confirmed (141 preinvasive lesions and 165 invasive lesions). Arc concave sign was defined as smooth and sunken part of the edge of the lesion on thin-section computed tomography (TSCT). The degree of arc concave sign was expressed by the arc chord distance to chord length ratio (AC-R); deep arc concave sign was defined as AC-R larger than the optimal cut-off value. Logistic regression analysis was used to identify the independent risk factors of invasiveness. RESULTS: Arc concave sign was observed in 65 of 306 pGGNs (21.2 %), and deep arc concave sign (AC-R > 0.25) were more common in invasive lesions (P = 0.008). Under microscope, interlobular septal displacements were found at tumour surface. Multivariate analysis indicated that irregular shape (OR, 3.558; CI: 1.374-9.214), presence of deep arc concave sign (OR, 3.336; CI: 1.013-10.986), the largest diameter > 10.1 mm (OR, 4.607; CI: 2.584-8.212) and maximum density > -502 HU (OR, 6.301; CI: 3.562-11.148) were significant independent risk factors of invasive lesions. CONCLUSIONS: Arc concave sign on TSCT is caused by interlobular septal displacement. The degree of arc concave sign can reflect the invasiveness of pGGNs. Invasive lesions can be effectively distinguished from preinvasive lesions by the presence of deep arc concave sign, irregular shape, the largest diameter > 10.1 mm and maximum density > -502 HU in pGGNs ≤ 20 mm.

Dynamic changes on chest CT of COVID-19 patients with solitary pulmonary lesion in initial CT.

PURPOSE: To investigate the dynamic evolution of image features of COVID-19 patients appearing as a solitary lesion at initial chest CT scan. MATERIALS AND METHODS: Twenty-two COVID-19 patients with solitary pulmonary lesion from three hospitals in China were enrolled from January 18, 2020 to March 18, 2020. The clinical feature and laboratory findings at first visit, as well as characteristics and dynamic evolution of chest CT images were analyzed. Among them, the CT score evaluation was the sum of the lung involvement in five lobes (0-5 points for each lobe, with a total score ranging from 0 to 25). RESULTS: 22 COVID-19 patients (11 males and 11 females, with an average age of 40.7 ± 10.3) developed a solitary pulmonary lesion within 4 days after the onset of symptoms, the peak time of CT score was about 11 days (with a median CT score of 6), and was discharged about 19 days. The peak of CT score was positively correlated with the peak time and the discharge time (p < 0.001, r = 0.793; p < 0.001, r = 0.715). Scan-1 (first visit): 22 cases (100%) showed GGO and one lobe was involved, CT score was 1.0/1.0 (median/IQR). Scan-2 (peak): 15 cases (68%) showed crazy-paving pattern, 19 cases (86%) showed consolidation, and 2.5 lobes were involved, CT score was 6.0/12.0. Scan-3 (before discharge): ten cases (45%) showed linear opacities, none had crazy-paving pattern, and 2.5 lobes were involved, CT score was 6.0/11.0. Scan-4 (after discharge): three cases (19%) showed linear opacities and one lobe was involved, CT score was 2.0/5.0. CONCLUSION: The chest CT features are related to the course of COVID-19 disease, and dynamic chest CT scan are helpful to monitor disease progress and patients' condition. In recovered patients with COVID-19, the positive CT manifestations were found within 4 days, lung involvement peaking at approximately 11 days, and discharged at about 19 days. The patients with more severe the lung injury was, the later the peak time appeared and the longer the recovery time was. Although the lesion was resolved over time, isolation and reexamination were required after discharge.

CT Manifestations of Coronavirus Disease (COVID-19) Pneumonia and Influenza Virus Pneumonia: A Comparative Study.

OBJECTIVE. The purpose of this study was to investigate differences in CT manifestations of coronavirus disease (COVID-19) pneumonia and those of influenza virus pneumonia. MATERIALS AND METHODS. We conducted a retrospective study of 52 patients with COVID-19 pneumonia and 45 patients with influenza virus pneumonia. All patients had positive results for the respective viruses from nucleic acid testing and had complete clinical data and CT images. CT findings of pulmonary inflammation, CT score, and length of largest lesion were evaluated in all patients. Mean density, volume, and mass of lesions were further calculated using artificial intelligence software. CT findings and clinical data were evaluated. RESULTS. Between the group of patients with COVID-19 pneumonia and the group of patients with influenza virus pneumonia, the largest lesion close to the pleura (i.e., no pulmonary parenchyma between the lesion and the pleura), mucoid impaction, presence of pleural effusion, and axial distribution showed statistical difference (p < 0.05). The properties of the largest lesion, presence of ground-glass opacity, presence of consolidation, mosaic attenuation, bronchial wall thickening, centrilobular nodules, interlobular septal thickening, crazy paving pattern, air bronchogram, unilateral or bilateral distribution, and longitudinal distribution did not show significant differences (p > 0.05). In addition, no significant difference was seen in CT score, length of the largest lesion, mean density, volume, or mass of the lesions between the two groups (p > 0.05). CONCLUSION. Most lesions in patients with COVID-19 pneumonia were located in the peripheral zone and close to the pleura, whereas influenza virus pneumonia was more prone to show mucoid impaction and pleural effusion. However, differentiating between COVID-19 pneumonia and influenza virus pneumonia in clinical practice remains difficult.

Risk Factors for The Growth of Residual Nodule in Surgical Patients with Adenocarcinoma Presenting as Multifocal Ground-glass Nodules.

PURPOSE: We aim to investigate the risk factors influencing the growth of residual nodule (RN) in surgical patients with adenocarcinoma presenting as multifocal ground-glass nodules (GGNs). METHOD: From January 2014 to June 2018, we enrolled 238 patients with multiple GGNs in a retrospective review. Patients were categorized into growth group 63 (26.5%), and non-growth group 175 (73.5%). The median follow-up time was 28.2 months (range, 6.3-73.0 months). To obtain the time of RN growth and find the risk factors for growth, data such as age, gender, history of smoking, history of malignancy, type of surgery, pathology and radiological characteristics were analyzed to use Kaplan-Meier method with the log-rank test and Cox regression analysis. RESULTS: The median growth time of RN was 56.0 months (95% CI, 45.0-67.0 months) in all 238 patients. Roundness (HR 4.62, 95% CI 2.20-9.68), part-solid nodule (CTR ≥ 50%) (HR 4.39, 95% CI 2.29-8.45), vascular convergence sign (HR 2.32, 95% CI 1.36-3.96) of RN, and age (HR 1.04, 95% CI 1.01-1.07) were independent predictors of further nodule growth. However, radiological characteristics and pathology of domain tumour (DT) cannot be used as indicators to predict RN growth. CONCLUSIONS: RN showed an indolent growth pattern in surgical patients with multifocal GGNs. RN with a higher roundness, presence of vascular convergence sign, more solid component, and in the elder was likely to grow. However, the growth of RN showed no association with the radiological features and pathology of DT.