No abstract

Thin-section computed tomography (TSCT) imaging biomarkers are uncertain to distinguish progressive adenocarcinoma from benign lesions in pGGNs. The purpose of this study was to evaluate the usefulness of TSCT characteristics for differentiating among transient (TRA) lesions, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) presenting as pure ground-glass nodules (pGGNs). Between January 2016 and January 2018, 255 pGGNs, including 64 TRA, 22 AAH, 37 AIS, 108 MIA and 24 IAC cases, were reviewed on TSCT images. Differences in TSCT characteristics were compared among these five subtypes of pGGNs. Logistic analysis was performed to identify significant factors for predicting MIA and IAC. Progressive pGGNs were more likely to be round or oval in shape, with clear margins, air bronchograms, vascular and pleural changes, creep growth, and bubble-like lucency than were non-progressive pGGNs. The optimal cut-off values of the maximum diameter for differentiating non-progressive from progressive pGGNs and IAC from non-IAC were 6.5 mm and 11.5 mm, respectively. For the prediction of IAC vs. non-IAC and non-progressive vs. progressive adenocarcinoma, the areas under the receiver operating characteristics curves were 0.865 and 0.783 for maximum diameter and 0.784 and 0.722 for maximum CT attenuation, respectively. The optimal cut-off values of maximum CT attenuation were −532 HU and −574 HU for differentiating non-progressive from progressive pGGNs and IAC from non-IAC, respectively. Maximum diameter, maximum attenuation and morphological characteristics could help distinguish TRA lesions from MIA and IAC but not from AAH. So, CT morphologic characteristics, diameter and attenuation parameters are useful for differentiating among pGGNs of different subtypes.

Controversy and challenges remain regarding the cognition of lung adenocarcinomas presented as subcentimeter ground glass nodules (GGNs). Postoperative lymphatic involvement or intrapulmonary metastasis is found in approximately 15% to 20% of these cases. This study aimed to develop and validate a radiomics signature to identify the invasiveness of lung adenocarcinoma appearing as subcentimeter ground glass nodules. We retrospectively enrolled 318 subcentimeter GGNs with histopathology-confirmed adenocarcinomas in situ (AIS), minimally invasive adenocarcinomas (MIA) and invasive adenocarcinomas (IAC). The radiomics features were extracted from manual segmentation based on contrast-enhanced CT (CECT) and non-contrast enhanced CT (NCECT) images after imaging preprocessing. The Lasso algorithm was applied to construct radiomics signatures. The predictive performance of radiomics models was evaluated by receiver operating characteristic (ROC) analysis. A radiographic-radiomics combined nomogram was developed to evaluate its clinical utility. The radiomics signature on CECT (AUC: 0.896 [95% CI 0.815–0.977]) performed better than the radiomics signature on NCECT data (AUC: 0.851[95% CI 0.712–0.989]) in the validation set. An individualized prediction nomogram was developed using radiomics model on CECT and radiographic model including type, shape and vascular change. The C index of the nomogram was 0.915 in the training set and 0.881 in the validation set, demonstrating good discrimination. Decision curve analysis (DCA) revealed that the proposed model was clinically useful. The radiomics signature built on CECT could provide additional benefit to promote the preoperative prediction of invasiveness in patients with subcentimeter lung adenocarcinomas.

BackgroundThere is accumulating evidence demonstrating that microRNAs (miRNA) play essential roles in proliferation, migration, and invasion of vascular smooth muscle cells (VSMCs). However, the exact function of these molecules and the mechanisms involved are not fully understood. In this study, we defined the role of miR-145-5p in VSMCs.Material/MethodsThis study used the PDGF-bb-induced VSMCs proliferation model. Expression of miR-145-5p and its target, Smad4, were detected and measured by real-time PCR and Western blot analysis. The luciferase reporter of miR-145-5p was used to elucidate miRNA-target interactions. The functions of miR-145-5p in proliferation and migration were detected by CCK-8 assay, Transwell assay, and scratch test.ResultsThis study demonstrates that miR-145-5p is downregulated in PDGF-mediated VSMCs in both time- and dose-dependent manners. The in vitro results suggest that overexpression of miR-145-5p results in a reduction in SMAD4 and an increase in SMAD2, Smad3, and TGF-β at the mRNA and protein levels. Overexpression of miR-145-5p inhibited PDGF-induced VSMCs proliferation and migration. Moreover, SMAD4 was identified as a direct target of miR-145-5p and is involved in PDGF-mediated VSMC proliferation. Downstream factors such as Smad2, Smad3, and TGF-β were also influenced by miR-145-5p.ConclusionsWe identify miR-145-5p as a novel regulator of VSMC. Moreover, miR-145-5p inhibits VSMCs proliferation and migration by directly targeting Smad4 and dysregulating the transforming growth factor-β signaling cascade, including Smad2, Smad3, and TGF-β.