Objective To explore the correlation between the quantitative and qualitative features of CT images and the invasiveness of pulmonary ground-glass nodules, providing reference value for preoperative planning of patients with ground-glass nodules. MethodsThe patients with ground-glass nodules who underwent surgical treatment and were diagnosed with pulmonary adenocarcinoma from September 2020 to July 2022 at the Third Affiliated Hospital of Kunming Medical University were collected. Based on the pathological diagnosis results, they were divided into two groups: a non-invasive adenocarcinoma group with in situ and minimally invasive adenocarcinoma, and an invasive adenocarcinoma group. Imaging features were collected, and a univariate logistic regression analysis was conducted on the clinical and imaging data of the patients. Variables with statistical difference were selected for multivariate logistic regression analysis to establish a predictive model of invasive adenocarcinoma based on independent risk factors. Finally, the sensitivity and specificity were calculated based on the Youden index. Results A total of 555 patients were collected. The were 310 patients in the non-invasive adenocarcinoma group, including 235 females and 75 males, with a meadian age of 49 (43, 58) years, and 245 patients in the invasive adenocarcinoma group, including 163 females and 82 males, with a meadian age of 53 (46, 61) years. The binary logistic regression analysis showed that the maximum diameter (OR=4.707, 95%CI 2.060 to 10.758), consolidation/tumor ratio (CTR, OR=1.027, 95%CI 1.011 to 1.043), maximum CT value (OR=1.025, 95%CI 1.004 to 1.047), mean CT value (OR=1.035, 95%CI 1.008 to 1.063), spiculation sign (OR=2.055, 95%CI 1.148 to 3.679), and vascular convergence sign (OR=2.508, 95%CI 1.345 to 4.676) were independent risk factors for the occurrence of invasive adenocarcinoma (P<0.05). Based on the independent predictive factors, a predictive model of invasive adenocarcinoma was constructed. The formula for the model prediction was: Logit(P)=–1.293+1.549×maximum diameter of lesion+0.026×CTR+0.025×maximum CT value+0.034×mean CT value+0.72×spiculation sign+0.919×vascular convergence sign. The area under the receiver operating characteristic curve of the model was 0.910 (95%CI 0.885 to 0.934), indicating that the model had good discrimination ability. The calibration curve showed that the predictive model had good calibration, and the decision analysis curve showed that the model had good clinical utility. Conclusion The predictive model combining quantitative and qualitative features of CT has a good predictive ability for the invasiveness of ground-glass nodules. Its predictive performance is higher than any single indicator.
ObjectiveTo assess the specific clinicopathological characteristics as well as prognostic value of prognostic significance of spread through air spaces (STAS) in lung adenocarcinoma.MethodsWe systematically searched the databases of PubMed, EMbase and Web of Science databases from their date of inception to March 2019. The quality of the included literature was assessed by the Newcastle-Ottawa scale (NOS). The NOS of the study higher than 6 points was considered as high quality. Software of Stata 12.0 was used for meta-analysis.ResultsTwenty retrospective cohort studies involved with totally 6 225 patients were included. Quality of included studies was high with NOS score equal or higher than 6 points. STAS was associated with male sex, ever smoking history, abnormal carcino-embryonic antigen (CEA) level, air bronchogram negative, anaplasticlymphoma kinase (ALK) arrangement positive, epidermal growth factor receptor (EGFR) mutation positive, advanced pathological tumor stage and more invasive pathological adenocarcinoma subtypes. The presence of STAS indicated significantly poor recurrence free survival (RFS) (HR=1.960, 95%CI 1.718-2.237, P<0.001) as well as poor overall survival (OS) (HR=1.891, 95%CI 1.389-2.574, P<0.001). Further subgroup analyses showed that exhibiting tumor size including diameter less than 2 cm (HR=2.344, 95%CI 1.703-3.225, P<0.001) and diameter over 2 cm (HR=2.571, 95%CI 1.559-4.238, P<0.001), resection type including lobectomy (HR=1.636, 95%CI 1.258-2.127, P<0.001) and sublobar resection (HR=3.549, 95%CI 2.092-6.021, P<0.001) in stageⅠ adenocarcinoma suggested that STAS had a bad effect on RFS.ConclusionPresence of STAS is associated with more aggressive clinicopathological features and independently associated with worse RFS and OS in lung adenocarcinoma. STAS positive has a negative effect on RFS whatever the tumor size (including the diameter<2 cm or >2 cm) and resection types in stageⅠ adenocarcinoma.
Objective To investigate the molecular mechanisms by which the long non-coding RNA (lncRNA) MIR223HG affects the proliferation, migration and apoptosis of lung adenocarcinoma cells. MethodsDNA damaging agent Zeocin was used to treat human embryo lung cell (MRC-5) and lung cancer cell (A549 and H1299), and the expression of MIR223HG was tested by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Moreover, the ataxia-telangiectasia mutated (ATM) protein and ATM pathway downstream factor Cell cycle checkpoint kinase 2 (Chk2), p53 tumor suppressor protein (p53) in the lung cancer cell (A549 and H1299) with Zeocin were also tested by qRT-PCR. Cell transfection and Transwell migration assay, colony formation assays, apoptosis assays were performed to verify the role of ATM in the expression of MIR223HG in lung adenocarcinoma. ResultsThe expression of MIR223HG was reduced markedly in the lung cancer cells (A549 and H1299) compared with human embryo lung cell (MRC-5) after treated with Zeocin. ATM protein and its downstream factors Chk2, p53 involved in the process, and ATM regulated the expression of MIR223HG in the lung cancer cells with Zeocin. Futhermore, ATM joined in the processes that MIR223HG regulated the lung cancer cells proliferation, migration and apoptosis. Conclusions The expression of MIR223HG is related to the DNA damage response in the lung cancer, and MIR223HG regulates lung cancer cells proliferation, migration and apoptosis by ATM/Chk2/p53 pathway. MIR223HG may be a potential therapeutic target for lung adenocarcinoma treatment.
This research is to explore the perfusion time-intensity curve parameters of a lung adenocarcinoma xenograft into nude mouse model with contrast enhanced ultrasonography (CEUS); and to investigate the angiogenesis features of tumor at different growth time. Twenty one lung adenocarcinoma xenografted nude mice were divided into three groups and inculcated with human lung adenocarcinoa. Time window for examining CEUS were respectively in 7-day, 14-day and 28-day. The perfusion parameters including rise time (RT), peak intensity (PI), area under the curve (AUC) of lung tumor were obtained on CEUS images by using off-line software Q lab. Immunohistochemically staining for CD34 was used to observe the microvessel density (MVD).The 7-day group had the highest AUC and PI; AUC and PI of 14-day and 28-day group decreased gradually (P < 0.05). RT was increased as tumor growth. In tumor with necrosis, AUC and PI of non-necrosis part were also larger than necrosis part (P < 0.05). Immunohistochemically staining for CD34 of all tumors reflected that the density of microvessels in necrosis tumor was significantly higher than those without necrosis (7.50±3.44 vs.12.44±5.74, P=0.034). Pearson correlation indicated that PI was positively related with MVD (r=0.668, P=0.008). Lung adenocarcinoma perfusion characteristic can be accessed from time-intensity curve parameters by using noninvasively and non-radiative contrast enhanced ultrasonography. Time-intensity curve parameters including AUC, PI and RT may reflect tumor angiogenesis.
Objective To investigate the effects of growth differentiation factor 15 (GDF15) on lung adenocarcinoma bone metastasis in nude mice by regulating phosphatase and tensin homology/phosphatidylinositol 3 kinase/protein kinase B (PTEN/PI3K/AKT) signaling pathway. Methods The bone metastasis model of lung adenocarcinoma in nude mice was established and mice were randomly divided into Control group, sh-NC group, sh-GDF15 group, sh-GDF15+sh-NC group and sh-GDF15+sh-PTEN group. The changes of 50% pain withdrawl threshold (PWT) and thermal withdrawal latency (TWL) were observed. bone destruction was analyzed by Micro-CT. Bone morphology was observed by HE staining. The expression of osteoclast-related factors was detected by immunohistochemistry. The expression of PTEN/PI3K/AKT signaling pathway was detected by Western blot. Results The tibia tissue of nude mice in Control group and sh-NC group was destroyed, the continuity of bone cortex was interrupted, obvious bone tumor lesions were observed, the tumor cells were irregular in shape, densely distributed and disordered, and the nuclei were obviously deformed. Compared with sh-NC group, sh-GDF15 group had less tibial tissue destruction, the bone tumor cell density was significantly reduced, the pathological morphology was significantly improved, and 50% PWT, TWL, bone mineral density (BMD), trabecular bone volume/total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and PTEN expression were increased, the expressions of trabecular separation (Tb.Sp), cathepsin K (CTSK), matrix metalloproteinase 9 (MMP-9), p-PI3K PI3K and p-Akt/Akt were decreased (P<0.05). Compared with sh-GDF15+sh-NC group, sh-GDF15+sh-PTEN group had severe tibial tissue damage, the bone tissue tumor cells were dense and the pathological injury was aggravated, and 50%PWT, TWL, BMD, BV/TV, Tb.N, Tb.Th and PTEN expression were decreased, the expressions of Tb.Sp, CTSK, MMP-9, p-PI3K /PI3K and p-Akt /Akt were increased (P<0.05). Conclusion GDF15 can promote bone metastasis of lung adenocarcinoma in nude mice, and its mechanism is related to inhibition of PTEN/PI3K/AKT signaling pathway.
ObjectiveTo analyze the expression of cold-induced RNA-binding protein (CIRBP) in lung adenocarcinoma and its clinical significance based on bioinformatics, in order to provide a new direction for the study of therapeutic targets for lung adenocarcinoma.MethodsThe CIRBP gene expression data and patient clinical information data in lung adenocarcinoma tissues and adjacent tissues were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. The expression of CIRBP in lung adenocarcinoma was analyzed. Furthermore, its relationship with clinicopathological features and prognosis in patients with lung adenocarcinoma was analyzed. GO and KEGG enrichment analysis were carried out for the screened genes. The CIRBP protein interaction network was constructed by STRING, and the correlation analysis was carried out using the GEPIA online website.ResultsThe expression level of CIRBP gene in lung adenocarcinoma tissues was significantly lower than that in adjacent tissues (P<0.01), and its expression level was correlated with T stage and N stage in clinicopathological features. The prognosis of patients with high CIRBP expression in lung adenocarcinoma was significantly better than that with low CIRBP expression. Univariate and multivariate Cox regression analysis showed that CIRBP was an independent prognostic factor in patients with lung adenocarcinoma. GO functional annotation showed its enrichment in organelle fission, nuclear fission, chromosome separation, and DNA replication, etc. KEGG analysis showed that it was mainly involved in cell cycle and DNA replication. Protein interaction network and GEPIA online analysis showed that the expression level of CIRBP was negatively correlated with the expression level of cyclin B2.ConclusionCIRBP gene is down-regulated in lung adenocarcinoma tissues, and its expression level is closely related to patient prognosis. CIRBP gene may be a potential therapeutic target and prognostic marker for lung adenocarcinoma.
Objective To explore the correlation between the imaging features of peripheral ground-glass pulmonary nodules and the invasion degree of lung adenocarcinoma, and the high risk factors for infiltrating lung adenocarcinoma under thin-slice CT, which provides some reference for clinicians to plan the surgical methods of pulmonary nodules before operation and to better communicate with patients, and assists in building a clinical predictive model for invasive adenocarcinoma. MethodsClinical data of the patients with peripheral ground-glass pulmonary nodules (diameter≤3 cm) in thin-slice chest CT in the First Affiliated Hospital of Soochow University from January 2019 to January 2020 were continuously collected. All patients underwent thin-slice CT scan and thoracoscopic surgery in our center. According to the pathological examination results, they were divided into two groups: an adenocarcinoma lesions before infiltration group, and an invasive lung adenocarcinoma group. The thin-slice CT imaging parameters of pulmonary nodules were collected. The nodular diameter, mean CT value, consolidation tumor ratio (CTR), nodular shape, vacuolar sign, bronchial air sign, lobulation sign, burr sign, lesion boundary, pleural depression sign, vascular cluster sign and other clinical data were collected. Univariate and multivariate analyses were conducted to analyze the independent risk factors for the infiltrating lung adenocarcinoma, and to analyze the threshold value and efficacy of each factor for the identification of infiltrating lung adenocarcinoma. Results Finally 190 patients were enrolled. There were 110 patients in the adenocarcinoma lesions before infiltration group, including 21 males and 89 females with a mean age of 53.57±10.90 years, and 80 patients in the invasive lung adenocarcinoma group, including 31 males and 49 females with a mean age of 56.45±11.30 years. There was a statistical difference in the mean CT value, nodular diameter, CTR, gender, smoking, nodular type, nodular shape, vacuolar sign, lobulation sign, burr sign, lesion boundary, pleural depression sign, vascular cluster sign between the two groups (P＜0.05). However, there was no statistical difference between the two groups in age (P=0.081), lesion site (P=0.675), and bronchial air sign (P=0.051). Multiple logistic regression analysis showed that nodular diameter, mean CT value, CTR and lobulation sign were independent risk factors for differentiating preinvasive adenocarcinoma from invasive adenocarcinoma. At the same time, the threshold value was calculated by Youden index, indicating that the CTR was 0.45, the nodal diameter was 10.5 mm and the mean CT value was –452 Hu. Conclusion In the peripheral ground-glass pulmonary nodules, according to the patient's CT imaging features, such as mixed ground-glass nodules, irregular shapes, vacuoles, short burrs, clear boundaries, pleural indentations, and vascular clusters, have a certain reference value in the discrimination of the invasion degree of ground-glass pulmonary nodules. At the same time, it is found in this research that peripheral ground-glass pulmonary nodules with diameter greater than 10.5 mm, CT value greater than –452 Hu, CTR greater than 0.45 and lobulation sign are more likely to be infiltrating lung adenocarcinoma.
ObjectiveTo investigate the association between the baseline 18F-FDG PET/CT SUVmax and histological subtypes of ≤2 cm early peripheral lung adenocarcinoma (cN0).MethodsWe retrospectively reviewed the clinical data of consecutive patients who received baseline 18F-FDG PET/CT and underwent anatomic lung resection for ≤2 cm early peripheral lung adenocarcinoma from 2011 to 2014 in our institute.ResultsA total of 195 patients were enrolled in this study, including 86 males and 109 females, with an average age of 59.96±9.19 years. Twenty-two patients were pathologically confirmed with lymph node metastasis. One hundred and fifty-seven patients were in the subtype group 1, which included lepidic, acinar, and papillary predominant tumors. Thirty-eight patients were in the subtype group 2, which included solid and micropapillary predominant tumors. The 5-year survival rate was 79.0% and 58.0% in the subtype group 1 and subtype group 2, respectively (P=0.006). The median SUVmax was 2.00 (0.30-13.10) and 4.15 (1.20-17.90) in the subtype group 1 and subtype group 2, respectively (P=0.000). Logistic regression suggested that baseline SUVmax≥2.5 was an independent risk factor for the subtype group 2 (OR=6.635, 95%CI 2.510-17.545, P=0.000). The receiver operating characteristic curve suggested that the continuous SUVmax had an moderate predictive value for subtypes (area under the curve was 0.792, 95%CI 0.717-0.866).ConclusionBaseline 18F-FDG PET/CT SUVmax has certain predictive value for histological subtypes of ≤2 cm early peripheral lung adenocarcinoma.
ObjectiveTo evaluate the application value of three-dimensional (3D) reconstruction in preoperative surgical diagnosis of new classification criteria for lung adenocarcinoma, which is helpful to develop a deep learning model of artificial intelligence in the auxiliary diagnosis and treatment of lung cancer.MethodsThe clinical data of 173 patients with ground-glass lung nodules with a diameter of ≤2 cm, who were admitted from October 2018 to June 2020 in our hospital were retrospectively analyzed. Among them, 55 were males and 118 were females with a median age of 61 (28-82) years. Pulmonary nodules in different parts of the same patient were treated as independent events, and a total of 181 subjects were included. According to the new classification criteria of pathological types, they were divided into pre-invasive lesions (atypical adenomatous hyperplasia and and adenocarcinoma in situ), minimally invasive adenocarcinoma and invasive adenocarcinoma. The relationship between 3D reconstruction parameters and different pathological subtypes of lung adenocarcinoma, and their diagnostic values were analyzed by multiplanar reconstruction and volume reconstruction techniques.ResultsIn different pathological types of lung adenocarcinoma, the diameter of lung nodules (P<0.001), average CT value (P<0.001), consolidation/tumor ratio (CTR, P<0.001), type of nodules (P<0.001), nodular morphology (P<0.001), pleural indenlation sign (P<0.001), air bronchogram sign (P=0.010), vascular access inside the nodule (P=0.005), TNM staging (P<0.001) were significantly different, while nodule growth sites were not (P=0.054). At the same time, it was also found that with the increased invasiveness of different pathological subtypes of lung adenocarcinoma, the proportion of dominant signs of each group gradually increased. Meanwhile, nodule diameter and the average CT value or CTR were independent risk factors for malignant degree of lung adenocarcinoma.ConclusionImaging signs of lung adenocarcinoma in 3D reconstruction, including nodule diameter, the average CT value, CTR, shape, type, vascular access conditions, air bronchogram sign, pleural indenlation sign, play an important role in the diagnosis of lung adenocarcinoma subtype and can provide guidance for personalized therapy to patients in clinics.
ObjectiveTo investigate the expression of major histocompatibility complex, classⅡ, DQ alpha 1 (HLA-DQA1) in lung adenocarcinoma and its prognostic significance. MethodsThe prognostic significance of HLA-DQA1 in lung adenocarcinoma was determined by constructing receiver operating characteristic (ROC) curve and Kaplan-Meier curve, and functional analysis was performed using gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and cancer single-cell state atlas (CancerSEA). The association between the level of immune cell infiltration and HLA-DQA1 expression was evaluated using CIBERSORT and Spearman correlation analysis. Clinicopathological data of patients with lung adenocarcinoma who were hospitalized for surgical treatment at the North China University of Science and Technology Affiliated Hospital from 2022 to 2023 were collected, and the relationship between HLA-DQA1 expression and clinicopathological features of lung adenocarcinoma patients was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry in vitro experiments. ResultsA total of 30 patients were included in the study, including 17 females and 13 males, with 20 patients aged ≥60 years and 10 patients aged <60 years. Compared with normal tissue, the expression level of HLA-DQA1 in lung adenocarcinoma was significantly lower, as confirmed by qRT-PCR and immunohistochemistry in lung adenocarcinoma and normal lung tissue. CancerSEA, GO, and KEGG analyses indicated that HLA-DQA1 was closely related to the immune infiltration of tumor cells. Drug sensitivity analysis showed that patients with high HLA-DQA1 expression may be resistant to crizotinib treatment, while they were relatively sensitive to cisplatin, paclitaxel, docetaxel, and epidermal growth factor receptor inhibitors. ConclusionHLA-DQA1 is an important prognostic marker for patients with lung adenocarcinoma.
