Objective To investigate the clinical and pathological characteristics, prognosis and treatment strategies of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA). Methods We retrospectively analyzed the clinical data of 489 patients with AIS and MIA in our hospital from January 2007 to August 2015. There were 122 males and 367 females with an average age of 26–78 (51±9) years. According to the pathological types, they were divided into the AIS group (246 patients) and the MIA group (243 patients). In the AIS group, there were 60 males and 186 females with an average age of 50±7 years. In the MIA group, there were 62 males and 181 females with an average age of 54±5 years. The clinicopathological features, surgical methods and prognosis of the two groups were compared. Results There were significant differences in age, value of carcino-embryonic antigen (CEA), nodule shape and nodule size between the AIS and MIA groups (P<0.05). AIS patients were mostly under the age of 60 years with the value of CEA in the normal range which often appeared as pure ground-glass opacity lung nodules <1 cm in diameter on the CT scan. MIA often appeared as mixed ground-glass nodules <1.5 cm in diameter, accompanied by bronchiectasis and pleural indentation. The 5-year disease-free survival rate of the AIS and MIA groups reached 100%, and there was no statistical difference in the prognosis between the two groups after subtotal lobectomy (pulmonary resection and wedge resection) and lobectomy, systematic lymph node dissection and mediastinal lymph node sampling. Conclusion The analysis of preoperative clinical and imaging features can predict the AIS and MIA and provide individualized surgery and postoperative treatment program.
Objective To investigate the effects of tobacco smoke exposure on histone deacetylase 2 (HDAC2),interleukin-8(IL-8)and tumor necrosis factor-α(TNF-α)expression in peripheral blood of patients with lung adenocarcinoma and analyze the relationships among them. Methods Seventy-three cases diagnosed as lung adenocarcinoma were collected in the First Affiliated Hospital and Affiliated Tumor Hospital of Guangxi Medical University from April 2014 to March 2015.All patients underwent lung function test preoperatively.Fourteen healthy volunteers without tobacco smoke exposure and chronic obstructive pulmonary disease (COPD)were recruited as healthy control.According to the lung function and tobacco smoke exposure,all cases were divided into four groups,ie. a healthy control group (group A,14 cases),a group without tobacco smoke exposure and COPD(group B,19 cases),a group with tobacco smoke exposure and without COPD(group C,33 cases),and a group with tobacco smoke exposure and COPD(group D,21 cases).The expressions of HDAC2 mRNA,IL-8 mRNA and TNF-α mRNA in peripheral blood mononuclear cells (PBMCs)were detected by real-time polymerase chain reaction (PCR).The contents of IL-8 and TNF-α in serum were detected by ELISA. Results Compared with group A,the HDAC2 mRNA expression in PBMCs had no difference in group B(P>0.05),and was down-regulated significantly in group C and D (P<0.05),which in group D was the most obvious.Compared with group A,the expressions of IL-8 mRNA and TNF-α mRNA in PBMCs and the contents of IL-8 and TNF-α in serum were significantly higher in all lung adenocarcinoma patients(all P<0.05),and the up-regulation was more obvious in group D.The relative expression of HDAC2 mRNA in PBMCs showed no significant difference with respect to age,gender or TNM stage (P>0.05).IL-8 and TNF-α in PBMCs and serum showed no significant difference with respect to age and gender (P>0.05),and were higher in the patients with TNM stage Ⅲ lung adenocarcinoma than those with stage Ⅰ and Ⅱ(P<0.05),with no obvious difference between stage Ⅰ and stage Ⅱ (P>0.05). Conclusion Tobacco smoke exposure causes lower expression of HDAC2 and over-expression of IL-8 and TNF-α in peripheral blood of patients with lung adenocarcinoma,can aggravate inflammatory response especially when complicated with COPD,which may be related to the prognosis of lung adenocarcinoma.
ObjectiveTo explore the mechanism of dihydrouridine synthase 4-like (DUS4L) on the development of lung adenocarcinoma (LUAD).MethodsThe RNA-seq expression data of LUAD was downloaded from The Cancer Genome Atlas (TCGA), and the relationship between its clinical pathological characteristics and DUS4L mRNA expression was evaluated. The effect of DUS4L knockdown on the proliferation of A549 cells was detected by EDU proliferation assay. The gene expression profile of lung adenocarcinoma A549 cells in the DUS4L knockdown group (KD group) and control group (NC group) was detected by transcriptome sequencing technique. The differential genes were screened by DESeq2. ClusterProfiler was used to perform GO functional enrichment analysis of differential genes.ResultsThe expression of DUS4L mRNA in LUAD tissues was higher than that in normal tissues, and the up-regulation of DUS4L was related to the clinical pathological characteristics of LUAD patients. EDU proliferation assay suggested that knocking down DUS4L could inhibit the proliferation of A549 cells. A total of 456 differential genes were screened, including 289 up-regulated genes and 167 down-regulated genes [|log2(fold change)|>1 and Padj<0.05]. STC2 and TRIB3 were significantly down-regulated (P<0.05). Differential genes were mainly involved in the production of interleukin-8, angiogenesis, vascular endothelial cell proliferation and other biological pathways.ConclusionDUS4L can widely regulate the gene expression of LUAD cells, which provides a new idea for further studying the function and role of DUS4L in the occurrence and development of LUAD and finding new therapeutic targets for LUAD.
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 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.
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.
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.
ObjectiveTo explore and analyze the risk factors of pleural invasion in patients with small nodular type stage ⅠA pulmonary adenocarcinoma.MethodsFrom June 2016 to December 2017, 168 patients with small nodular type stage ⅠA pulmonary adenocarcinoma underwent surgical resection in the First Affiliated Hospital of Nanjing Medical University. There were 59 males and 109 females aged 58.7±11.5 years ranging from 28 to 83 years. The clinical data were analyzed retrospectively. Single factor Chi-square test and multivariate logistic regression were used to analyze the independent risk factors of pleural invasion.ResultsAmong 168 patients, 20 (11.9%) were pathologically confirmed with pleural invasion and 148 (88.1%) with no pleural invasion. Single factor analysis revealed significant differences (P<0.05) in nodule size, nodule status, pathological type, relation of lesion to pleura (RLP), distance of lesion to pleura (DLP), epidermal growth factor receptor (EGFR) mutation between patients with and without pleural invasion in stage ⅠA pulmonary adenocarcinoma. Logistic multivariate regression analysis showed that significant differences of nodule size, nodule status, RLP, DLP and EGFR mutation existed between the two groups (P<0.05), which were independent risk factors for pleural invasion.ConclusionImageological-pathological-biological characteristics of patients with small nodular type stage ⅠA pulmonary adenocarcinoma are closely related to pleural invasion. The possibility of pleural invasion should be evaluated by combining these parameters in clinical diagnosis and treatment.
Survivin-D53A (SVV-D53A) is a dominant-negative mutant survivin, which represents a potential promising target for cancer gene therapy. The present study was designed to determine whether SVV-D53A plasmid encapsuled by DOTAP: Chol liposome would have the anti-tumor activity against SPC-A1 lung adenocarcinoma, and to detect the possible mechanisms. In our experiment, SPC-A1 cells were transfected in vitro with SVV-D53A plasmid and examined for protein expression by Western blot, then flow cytometric analysis was used to detect apoptosis. SPC-A1 lung adenocarcinoma xenografts were established in vivo in the nude mice, which received the i.v. administrations of SVV-D53A plasmid/liposome complexes. After mice were sacrificed, the paraffin-embedded tumor tissue sections were used for proliferating cell nuclear antigen (PCNA) expression and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)assay. Compared with the control group, the mice treated with SVV-D53A plasmid had an obviously reduced tumor volume, with high level of apoptosis and decreased cell proliferation in tumor tissue. The research results proved that the administration of SVV-D53A plasmid resulted in significant inhibition of SPC-A1 cells both in vitro and in vivo. The functional mechanism is that the anti-tumor response causes and induces tumor cell apoptosis.