Objective To investigate the biological characteristics and clinical significance of cuproptosis-related genes in lung adenocarcinoma (LUAD) based on the multi-omics data from The Cancer Genome Atlas. Methods The cuproptosis-related genes were obtained from a study published in Science in March 2022. The whole genome data were used to reveal the mutation spectrum and copy number variation landscape of cuproptosis-related genes in LUAD and analyze its effects on transcriptome expression. Cuproptosis-related genes were annotated using Metascape analysis to further understand the pathways or functions in which these genes were involved. Subsequent univariate Cox analysis and Kaplan-Meier methods determined the prognosis of these genes in LUAD patients, and CellMiner analysis were used to identify those potential anticancer drugs for potentially targeting cuproptosis-related genes. Results Cuproptosis-related genes were less frequently mutated in LUAD, and the effect of gene mutations on transcriptomic expression may depend on the type of mutation. Gene copy number variation was an important factor resulting in the disordered expression of cuproptosis-related genes. The 16 cuproptosis-related genes were mainly involved in glyoxylate metabolism and glycine degradation, copper ion entry, proteolitidylation, cellular amino acid catabolism process, oxidative stress response, etc. Among them, 6 genes (DLD, FDX1, DLAT, DLST, PDHA1, CDKN2A) were prognostic risk genes in LUAD. The CellMiner analysis suggested that 13 drugs were associated with 7 cuproptosis-related genes and they might be potential anticancer drugs for potentially targeting cuproptosis. Conclusion This study reveals the biological characteristics and clinical significance of cuproptosis-related genes in LUAD, and provides some reference and theoretical basis for the subsequent research of cuproptosis in cancer.
ObjectiveTo compare the the effectiveness of robot-assisted thoracic surgery (RATS) with video-assisted thoracic surgery (VATS), in stageⅠ lung adenocarcinoma.MethodsFrom January 2012 to December 2018, 291 patients were included. The patients were allocated into two groups including a RATS group with 125 patients and a VATS group with 166 patients. Two cohorts (RATS, VATS ) of clinical stageⅠ lung adenocarcinoma patients were matched by propensity score. Then there were 114 patients in each group (228 patients in total). There were 45 males and 69 females at age of 62±9 years in the RATS group; 44 males, 70 females at age of 62±8 years in the VATS group. Overall survival (OS) and disease-free survival (DFS) were assessed. Univariate and multivariate analyses were performed to identify factors associated with the outcomes.Results Compared with the VATS group, the RATS group got less blood loss (P<0.05) and postoperative drainage (P<0.05) with a statistical difference. There was no statistical difference in drainage time (P>0.05) or postoperative hospital stay (P>0.05) between the two groups. The RATS group harvested more stations and number of the lymph nodes with a statistical difference (P<0.05). There was no statistical difference in 1-year, 3-year and 5-year OS and mean survival time (P>0.05). While there was a statistical difference in DFS between the two groups (1-year DFS: 94.1% vs. 95.6%; 3-year DFS: 92.6% vs. 75.2%; 5-year DFS: 92.6% vs. 68.4%, P<0.05; mean DFS time: 78 months vs. 63 months, P<0.05) between the two groups. The univariate analysis found that the number of the lymph nodes dissection was the prognostic factor for OS, and tumor diameter, surgical approach, stations and number of the lymph nodes dissection were the prognostic factors for DFS. However, multivariate analysis found that there was no independent risk factor for OS, but the tumor diameter and surgical approach were independently associated with DFS.ConclusionThere is no statistical difference in OS between the two groups, but the RATS group gets better DFS.
ObjectiveTo investigate the relationship between the expression of programmed cell death ligand-1 (PD-L1) and the maximal standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and the correlation of clinical factors between SUVmax values and PD-L1.MethodsThe clinical data of 84 patients with invasive lung adenocarcinoma diagnosed pathologically in West China Hospital, Sichuan University from August 2016 to November 2018 were analyzed retrospectively, including 38 males and 46 females, aged 60 (32-85) years. The tumor was acinar-predominant in 37 patients, papillary in 20, lepidic in 19, solid in 5 and micropapillary in 3. Multivariate analysis of the relationship between SUVmax value and other clinicopathological features was performed by linear regression. Logistic regression analysis was used to analyze the relationship between PD-L1 protein expression and other pathological features.ResultsThe SUVmax of the PD-L1 expression group was significantly higher than that of the non-PD-L1 expression group in the whole invasive lung adenocarcinoma group (P=0.002) and intermediate-grade histologic subtype (P=0.016). The SUVmax cut-off value of PD-L1 expression in the whole invasive lung adenocarcinoma group and intermediate-grade histologic subtype was 5.34 (AUC: 0.732, P=0.002) and 5.34 (AUC: 0.720, P=0.017), respectively. Multivariate analysis showed that pleura involvement, vascular tumor thrombus and the increase of tumor diameter could cause the increase of the SUVmax value, while the SUVmax value decreased in the moderately differentiated tumor compared with the poorly differentiated tumor. The SUVmax cut-off value between low-grade histologic subtype and intermediate-grade histologic subtype, intermediate-grade histologic subtype and high-grade histologic subtypes was 1.54 (AUC: 0.854, P<0.001) and 5.79 (AUC: 0.889, P<0.001), respectively. Multivariate analysis of PD-L1 expression showed pleura involvement (P=0.021, OR=0.022, 95%CI 0.001 to 0.558) and moderate differentiation (opposite to poor differentiation) (P=0.004, OR=0.053, 95%CI 0.007 to 0.042) decreased the expression of PD-L1.ConclusionThe SUVmax of the PD-L1 expression group is significantly higher than that of the non-PD-L1 expression group in the whole invasive lung adenocarcinoma group and intermediate-grade histologic subtype. The level of SUVmax and the expression of PD-L1 in invasive lung adenocarcinoma are related to many clinical factors.
ObjectiveTo investigate the correlation between UBE2Q1 expression and clinicopathologic features and prognosis of lung adenocarcinoma. MethodsThis study retrospectively chose the cancer tissue and para-carcinoma tissue samples of 74 patients with stage I to III lung adenocarcinoma who received radical resection in Nanjing Chest Hospital from January 2013 to December 2016. Immunohistochemistry staining was used to detect the expression level of UBE2Q1, and patients were divided into high-expression group and low-expression group according to the Immunohistochemistry staining score. The correlation of UBE2Q1 expression level and clinicopathological characteristics was analyzed by Chi-square test. Kaplan-Meier survival curve analyzed the correlation between UBE2Q1 and prognosis of lung adenocarcinoma patients. The risk factors affecting the survival of lung adenocarcinoma patients were analyzed by univariate and multivariate Cox proportional risk models. ResultsUBE2Q1 was highly expressed in lung adenocarcinoma tissues, and the expression level was correlated with tumor diameter, lymph node metastasis, and TNM stage (P<0.05), and did not correlate with patients’ gender, age, smoking history, and tumor differentiation (P>0.05). The results of the Kaplan-Meier survival analysis showed that patients with low expression of UBE2Q1 compared with those with high expression of UBE2Q1 had longer DFS and OS (both P<0.05). Cox proportional risk model showed that tumor diameter, lymph node metastasis, TNM stage, and high UBE2Q1 expression were the risk factors for DFS and OS, among which TNM stage was an independent risk factor. ConclusionUBE2Q1 was highly expressed in lung adenocarcinoma tissues and correlated with large tumor diameter, lymph node metastasis, late TNM stage and poorer prognosis in lung adenocarcinoma, and UBE2Q1 was a risk factor for lung adenocarcinoma.
Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.
ObjectiveTo compare the clinical effects of segmentectomy and lobectomy for ≤2 cm lung adenocarcinoma with micropapillary and solid subtype negative by intraoperative frozen sections.MethodsThe patients with adenocarcinoma who received segmentectomy or lobectomy in multicenter from June 2020 to March 2021 were included. They were divided into two groups according to a random number table, including a segmentectomy group (n=119, 44 males and 75 females with an average age of 56.6±8.9 years) and a lobectomy group (n=115, 43 males and 72 females with an average of 56.2±9.5 years). The clinical data of the patients were analyzed.ResultsThere was no significant difference in the baseline data between the two groups (P>0.05). No perioperative death was found. There was no statistical difference in the operation time (111.2±30.0 min vs. 107.3±34.3 min), blood loss (54.2±83.5 mL vs. 40.0±16.4 mL), drainage duration (2.8±0.6 d vs. 2.6±0.6 d), hospital stay time (3.9±2.3 d vs. 3.7±1.1 d) or pathology staging (P>0.05) between the two groups. The postoperative pulmonary function analysis revealed that the mean decreased values of forced vital capacity and forced expiratory volume in one second percent predicted in the segmentectomy group were significantly better than those in the lobectomy group (0.2±0.3 L vs. 0.4±0.3 L, P=0.005; 0.3%±8.1% vs. 2.9%±7.4%, P=0.041).ConclusionSegmentectomy is effective in protecting lungs function, which is expected to improve life quality of patients.
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.
With the development of multi-slice spiral computed tomography (CT) technology and the popularization of low-dose spiral CT screening, more and more adenocarcinomas presenting ground-glass nodule (GGN) are found. Pathological invasiveness is one of the important factors affecting the choice of treatment strategy and prognosis of patients with early lung adenocarcinoma. Imaging features have attracted wide attention due to their unique advantages in predicting the pathologic invasiveness of early lung adenocarcinoma. The imaging characteristics of GGN can be used to predict the pathologic invasiveness of lung adenocarcinoma and provide evidence for clinical decisions. However, the imaging parameters and numerical values for predicting pathologic invasiveness are still controversial, which will be reviewed in this paper.
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.
Objective To investigate the expression of SAPCD2 in the lung adenocarcinoma cells, and to study the effect of SAPCD2 regulating Hippo signaling pathway on the proliferation, invasion, migration and apoptosis of the lung adenocarcinoma cells and its mechanism. Methods Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression levels of SAPCD2 mRNA and protein in four types of lung cancer cells (HCC827, H1650, SK-MES-1, A549) and human normal lung epithelial cells (BESA-2B), respectively. Then, lung cancer cells with relatively high levels of SAPCD2 expression were selected for subsequent experiments. The experiment cells were divided into a normal control group (NC group), a si-SAPCD2 group, and a pathway inhibitor group (si-SAPCD2+XMU-MP-1 group). Firstly, SAPCD2 mRNA was silenced using small interfering RNA (siRNA) technology, and then qRT-PCR was used to detect the expression of SAPCD2 in transfected lung cancer cells; using clone plate assay to detect the proliferation of lung cancer cells after silencing; using flow cytometry to detect the apoptosis of lung cancer cells after silencing; observe the number of lung cancer cells at different stages through cell cycle experiments; then Transwell experiment was used to analyze the effect of silencing SAPCD2 on the migration and invasion of lung cancer cell migration. Finally, Western blot was used to detect the expression of ki-67, Bcl-2, Caspase-3, NF2, P-MST1, P-LATS1, P-YAP, YAP, and TAZ proteins.Results SAPCD2 had the highest expression level in lung adenocarcinoma A549 cells (P<0.01). Silencing SAPCD2 significantly decreased the proliferation ability of A549 cells (P<0.01), inhibited their migration (P<0.05) and invasion (P<0.01), and promoted A549 cell apoptosis (P<0.01); more than half of the cells remained in the G0/G1 phase. Compared with the NC group, A549 cells showed a significant increase in G0/G1 phase cells (P<0.01), a significant decrease in G2/M and S phase cells (P<0.01), and a significant increase in the proportion of early apoptotic cells (P<0.01). Western blot results showed that silencing SAPCD2 down-regulated the expression of ki-67, Bcl-2, YAP, and TAZ proteins compared to the NC group (P<0.01), and up-regulated the expression of Caspase-3, NF2, P-MST1, P-LATS1, and P-YAP proteins (P<0.01). Conclusions The expression of SAPCD2 in lung adenocarcinoma A549 cells is significantly higher than that in normal lung epithelial cells (BESA-2B), which promotes the proliferation, migration and invasion of A549 cells and inhibits apoptosis. The mechanism may be related to the inhibition of Hippo signaling pathway.