ObjectiveTo predict the probability of lymph node metastasis after thoracoscopic surgery in patients with lung adenocarcinoma based on nomogram. MethodsWe analyzed the clinical data of the patients with lung adenocarcinoma treated in the department of thoracic surgery of our hospital from June 2018 to May 2021. The patients were randomly divided into a training group and a validation group. The variables that may affect the lymph node metastasis of lung adenocarcinoma were screened out by univariate logistic regression, and then the clinical prediction model was constructed by multivariate logistic regression. The nomogram was used to show the model visually, the receiver operating characteristic (ROC) curve, calibration curve and clinical decision curve to evaluate the calibration degree and practicability of the model. ResultsFinally 249 patients were collected, including 117 males aged 53.15±13.95 years and 132 females aged 47.36±13.10 years. There were 180 patients in the training group, and 69 patients in the validation group. There was a significant correlation between the 6 clinicopathological characteristics and lymph node metastasis of lung adenocarcinoma in the univariate logistic regression. The area under the ROC curve in the training group was 0.863, suggesting the ability to distinguish lymph node metastasis, which was confirmed in the validation group (area under the ROC curve was 0.847). The nomogram and clinical decision curve also performed well in the follow-up analysis, which proved its potential clinical value. ConclusionThis study provides a nomogram combined with clinicopathological characteristics, which can be used to predict the risk of lymph node metastasis in patients with lung adenocarcinoma with a diameter≤3 cm.
Objective To analyze the effects of systematic lymph node dissection (SLND) and lobe-specific lymph node dissection (L-SND) on perioperative and long-term outcomes of patients with clinicalⅠA (cⅠA) stage lung adenocarcinoma. Methods A retrospective analysis was done on the patients with cⅠA stage lung adenocarcinoma who received thoracoscopic radical resection admitted to the Affiliated Hospital of Qingdao University from January 2013 to August 2016. Propensity score matching was conducted to eliminate the biases. The recurrence-free survival was compared between the two groups after matching. Perioperative parameters and postoperative complications were also analyzed. Results A total of 725 patients were enrolled, including 252 males and 473 females, with a median age of 62.0 (31.0-69.0) years. There were 228 patients in the L-SND group and 497 patients in the SLND group. After matching, there were 211 patients in each group and no statistical difference in the incidence of postoperative complications (10.9% vs. 13.7%, P=0.374), identification of metastatic positive lymph nodes (12.3% vs. 9.0%, P=0.270), or recurrence-free survival (P=0.492) were found between two groups, whereas the operation time (163.9±39.4 min vs. 135.4±32.4 min, P＜0.001), intraoperative blood loss [100.0 (20.0-800.0) mL vs. 100.0 (10.0-400.0) mL, P＜0.001], intubation time [4.0 (1.0-18.0) d vs. 4.0 (1.0-9.0) d, P＜0.001] and hospital stay (12.3±3.3 d vs. 10.8±2.4 d, P=0.003) in the SLND group were found to be significantly higher or longer than those in the L-SND group. Conclusion L-SND has a similar efficiency to SLND in terms of postoperative complications, pathological lymph node metastasis, and recurrence-free survival, as well as significant advantages in reducing intraoperative blood loss, and shortening operation time, intubation time and length of hospital stay. Therefore, L-SND can be recommended to replace SLND as a method for lymph node resection in patients with cⅠA stage lung adenocarcinoma.
Objective The management of pulmonary nodules is a common clinical problem, and this study constructed a nomogram model based on FUT7 methylation combined with CT imaging features to predict the risk of adenocarcinoma in patients with pulmonary nodules. Methods The clinical data of 219 patients with pulmonary nodules diagnosed by histopathology at the First Affiliated Hospital of Zhengzhou University from 2021 to 2022 were retrospectively analyzed. The FUT7 methylation level in peripheral blood were detected, and the patients were randomly divided into training set (n=154) and validation set (n=65) according to proportion of 7:3. They were divided into a lung adenocarcinoma group and a benign nodule group according to pathological results. Single-factor analysis and multi-factor logistic regression analysis were used to construct a prediction model in the training set and verified in the validation set. The receiver operating characteristic (ROC) curve was used to evaluate the discrimination of the model, the calibration curve was used to evaluate the consistency of the model, and the clinical decision curve analysis (DCA) was used to evaluate the clinical application value of the model. The applicability of the model was further evaluated in the subgroup of high-risk CT signs (located in the upper lobe, vascular sign, and pleural sign). Results Multivariate logistic regression analysis showed that female, age, FUT7_CpG_4, FUT7_CpG_6, sub-solid nodules, lobular sign and burr sign were independent risk factors for lung adenocarcinoma (P<0.05). A column-line graph prediction model was constructed based on the results of the multifactorial analysis, and the area under the ROC curve was 0.925 (95%CI 0.877 - 0.972 ), and the maximum approximate entry index corresponded to a critical value of 0.562, at which time the sensitivity was 89.25%, the specificity was 86.89%, the positive predictive value was 91.21%, and the negative predictive value was 84.13%. The calibration plot predicted the risk of adenocarcinoma of pulmonary nodules was highly consistent with the risk of actual occurrence. The DCA curve showed a good clinical net benefit value when the threshold probability of the model was 0.02 - 0.80, which showed a good clinical net benefit value. In the upper lobe, vascular sign and pleural sign groups, the area under the ROC curve was 0.903 (95%CI 0.847 - 0.959), 0.897 (95%CI 0.848 - 0.945), and 0.894 (95%CI 0.831 - 0.956). Conclusions This study developed a nomogram model to predict the risk of lung adenocarcinoma in patients with pulmonary nodules. The nomogram has high predictive performance and clinical application value, and can provide a theoretical basis for the diagnosis and subsequent clinical management of pulmonary nodules.
Objective To investigate the relationship between clinical features and lymph node metastasis in lung adenocarcinoma patients with T1 stage. Methods We retrospectively analyzed the clinical data of 253 T1-stage lung adenocarcinoma patients (92 males and 161 females at an average age of 59.45±9.36 years), who received lobectomy and systemic lymph node dissection in the Second Affiliated Hospital of Harbin Medical University from October 2013 to February 2016. Results Lymph node metastasis was negative in 182 patients (71.9%) and positive in 71 (28.1%). Poor differentiation (OR=6.988, P=0.001), moderate differentiation (OR=3.589, P=0.008), micropapillary type (OR=24.000, P<0.001), solid type (OR=5.080, P=0.048), pleural invasion (OR=2.347, P=0.024), age≤53.5 years (OR=2.594, P=0.020) were independent risk factors for lymph node metastasis. In addition, in the tumor with diameter≥1.55 cm (OR=0.615, P=0.183), although the cut-off value of 1.55 cm had no significant difference, it still suggested that tumor diameter was an important risk factor of lymph node metastasis. Conclusion In lung adenocarcinoma with T1 stage, the large tumor diameter, the low degree of differentiation, the high ratio of consolidation, and the micropapillary or solid pathological subtypes are more prone to have lymph node metastasis.
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 predictive value of thyroid transcription factor-1 (TTF-1) in the treatment of advanced lung adenocarcinoma with different chemotherapy regimens.MethodsA total of 126 patients with advanced lung cancer were divided into three groups according to the chemotherapy regimen, namely a pemetrexed+nedaplatin group (PEM+NDP group), a pemetrexed+cisplatin/carboplatin group (PEM+DDP/CBP group) and a third-generation (3G) chemotherapy+cisplatin/carboplatin group (3G agent+DDP/CBP group). The predictive value of TTF-1 in the above three treatment regimens was analyzed. The patients were followed up by telephone or outpatient visit until April 2017.ResultsThere were no significant differences in disease control rate or objective response rate between the three different chemotherapy regimens (all P>0.05). The survival rate of PEM+NDP group was significantly higher than that of PEM+DDP/CBP group and 3G agent+DDP/CBP group (9.68%vs. 5.56% and 6.80%, both P<0.05). ECOG score and brain metastasis were independent risk factors for the prognosis of chemotherapy regimens. TTF-1 was an independent risk factor for PEM+NDP therapy.ConclusionTTF-1 is an independent risk factor for PEM+NDP chemotherapy, but not for 3G agent + DDP/CBP or PEM+DDP/CBP regimens.
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 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.
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.
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.