Screening of novel tumor-associated antigens for lung adenocarcinoma mRNA vaccine development based on pyroptosis phenotype genes.

This study aimed to identify new pyroptosis-associated tumor antigens for use in mRNA vaccines and the screening of sensitive LUAD populations suitable for vaccination. The association between tumor immune infiltrating cell abundance and potential tumor antigens was investigated and visualized using the analysis modules of gene expression, clinical outcomes, and somatic copy number variation. In addition, the pyroptosis-related genes (PRGs) were clustered, the relative pyroptosis subtypes (PSs) and gene modules were identified, and the prognostic value of the PSs was examined. The expression of key PRGs in two lung adenocarcinoma cell lines was verified by RT-qPCR. Four tumor pyroptosis-associated antigens, CARD8, NAIP, NLRP1, and NLRP3, were screened as potential candidates for LUAD mRNA vaccine development. In the construction of consensus clusters for PRGs, two PSs, PS1 and PS2, were classified, in which patients with PS1 LUAD had a better prognosis. In contrast, patients with PS2 LUAD may have better responsiveness to mRNA vaccine treatment. The key PRGs can be regarded as biomarkers to predict the LUAD prognosis and identify patients suitable for mRNA vaccines. The RT-qPCR results showed that the expression levels of CSMD3, LRP1B, MUC16 and TTN were significantly increased in the two lung adenocarcinoma cell lines, while the expression levels of CARD8, TP53 and ZFHX4 were significantly reduced. The antigens CARD8, NAIP, NLRP1, and NLRP3, which are associated with tumor pyroptosis, could be candidate molecules for LUAD mRNA vaccine development. Patients with PS2 LUAD may be suitable candidates for mRNA vaccine treatment.

Transthyretin Suppressed Tumor Progression in Nonsmall Cell Lung Cancer by Inactivating MAPK/ERK Pathway.

Background: Lung malignancy is a main source of disease passing all throughout the planet, whereas the transthyretin (TTR) is a specific biomarker for clinical diagnosis. However, its role in lung malignancy stays to be obscure. Materials and Methods: In the current examination, the authors made an endeavor to research impact of abnormal expression of TTR on nonsmall cell lung carcinoma (NSCLC) by overexpression or knockdown of TTR. To further explore the instruments' fundamental mechanism part of TTR in NSCLC, several signal pathways were searched and verified. To confirm the effect of TTR overexpression on tumors, in vivo experiments were conducted. Result: It was found that upregulated TTR clearly stifled cell proliferation, migration, invasion, and expanded apoptosis. Significant suppression of phosphor-extracellular signal-regulated kinase (ERK) was observed in TTR-treated NSCLC cells, implying that TTR was important for cellular progress by regulating mitogen-activated protein kinase/ERK signaling pathway. In in vivo experiment, overexpression of TTR promoted cell apoptosis and inhibited tumor growth. Conclusion: Overall, the results suggest that TTR has a potential antitumor effect in human NSCLC progression, which provides theoretical basis for the diagnosis and treatment of NSCLC. Above all, further understanding of TTR was useful for clinical care. Clinical Trial Registration Number: 2016-08.

Perioperative outcomes of combined heart surgery and lung tumor resection: a systematic review and meta-analysis.

OBJECTIVE: The prevalence of patients with concomitant heart and lung lesions requiring surgical intervention is increasing. Simultaneous cardiac surgery and pulmonary resection avoids the need for a second operation. However, there are concerns regarding the potentially increased mortality and complication rates of simultaneous surgery and the adequacy of lung exposure during heart surgery. Therefore, we performed a meta-analysis to evaluate the perioperative mortality and complication rates of combined heart surgery and lung tumor resection. METHODS: A comprehensive literature search was performed in July 2020. The PubMed, Embase, and Web of Science databases were searched to identify studies that reported the perioperative outcomes of combined heart surgery and lung tumor resection. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias of included studies. Pooled proportions and 95% confidence intervals (95% CI) were calculated by R version 3.6.1 using the meta package. RESULTS: A total of 536 patients from 29 studies were included. Overall, the pooled proportion of operative mortality was 0.01 (95% CI: 0.00, 0.03) and the pooled proportion of postoperative complications was 0.40 (95% CI: 0.24, 0.57) for patients who underwent combined cardiothoracic surgery. Subgroup analysis by lung pathology revealed that, for patients with lung cancer, the pooled proportion of anatomical lung resection was 0.99 (95% CI: 0.95, 1.00) and the pooled proportion of systematic lymph node dissection or sampling was 1.00 (95% CI: 1.00, 1.00). Subgroup analysis by heart surgery procedure found that the pooled proportion of postoperative complications of patients who underwent coronary artery bypass grafting (CABG) patients using the off-pump method was 0.17 (95% CI: 0.01, 0.43), while the pooled proportion of complications after CABG using the on-pump method was 0.61 (95% CI: 0.38, 0.82). CONCLUSION: Combined heart surgery and lung tumor resection had a low mortality rate and an acceptable complication rate. Subgroup analyses revealed that most patients with lung cancer underwent uncompromised anatomical resection and mediastinal lymph node sampling or dissection during combined cardiothoracic surgery, and showed off-pump CABG may reduce the complication rate compared with on-pump CABG. Further researches are still needed to verify these findings.

Effect and Mechanism of Transthyretin over-Expression on Proliferation and Cell Cycle of Lung Cancer A549 Cells.

BACKGROUND: The effects of transthyretin (TTR) over-expression on the proliferation and cell cycle of non-small cell lung cancer (NSCLC) A549 cells and its possible mechanism were verified. METHODS: A total of 196 LC patients and 20 healthy controls were enrolled at Tianjin Hospital, Tianjin, China between Apr 2017 and Oct 2017. The serum TTR content was detected by ELISA. Through lentiviral transfection method, NSCLC cells were divided into non-transfected group (group A), negative control group (group B) transfected with empty vector and experimental group (group C) transfected with TTR over-expression. Cell proliferation was detected by CCK-8 method, TTR mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR), and TTR protein expression was tested by Western blot (WB). Cell cycle was detected by flow cytometry, Wnt3a/ß-catenin protein expression was detected by WB, and mRNA expression was detected by RT-qPCR. RESULTS: The serum TTR content in early, middle and late LC group was remarkably lower than that in healthy group (P<0.05). Compared with late stage, TTR content in early and middle stages of LC group was higher, and the difference was statistically marked (P < 0.05). The absorbance value of group C was lower than that of groups A and B, indicating that the cell proliferation activity dramatically decreased, with statistically marked difference (P<0.05). LC A549 cells in group C were obviously blocked in G2M, with statistical significance (P<0.05). CONCLUSION: TTR over-expression can inhibit the proliferation of NSCLC A549 cells, and the expression is related to Wnt3a/ß-catenin pathway. TTR in serum of patients was helpful for diagnosing LC and has certain clinical value.

Sublobar resection is associated with better perioperative outcomes in elderly patients with clinical stage I non-small cell lung cancer: a multicenter retrospective cohort study.

BACKGROUND: Sublobar resection has emerged as an alternative to lobectomy for management of early-stage non-small cell lung cancer (NSCLC). However, controversy remains as to whether it is adequate for elderly patients. The present study aimed to comparatively study the perioperative outcomes and overall survival of sublobar resection vs. lobectomy for management of elderly patients (≥65 years) with clinical stage I NSCLC. METHODS: This is a multicenter retrospective cohort study. Clinical stage I NSCLC patients who underwent lobar or sublobar resection (segmentectomy and wedge resection) at the Department of Thoracic Surgery of 10 tertiary hospitals between January 2014 and September 2017 were retrospectively reviewed from the national collaborative prospective lung cancer database (LinkDoc Technology Co, Ltd., Beijing, China). Clinical data on demographic and tumor characteristics, surgical details were collected. Perioperative outcomes and overall survival were analyzed by using propensity score matching to adjust for selection bias. Subgroup analysis was further carried out to explore the potential sources of heterogeneity. RESULTS: Among the 1,579 eligible patients, 1,164 (73.7%) underwent lobectomy and 415 (26.3%) underwent sublobar resection (106 segmentectomy and 309 wedge resection). Sublobar resection was more frequently performed in patients who were elder, had more comorbidities and smaller, left-sided adenocarcinoma (P<0.001). Propensity-matched analysis showed significant association of sublobar resection with less blood loss, shorter operation time, chest drainage and hospital stay, while with less lymph node removal when compared with lobectomy (P<0.001). Short term survival analysis showed comparable results even after adjusted in the matched analysis. Similar results were obtained when limiting patients to those aged >75 years, at pathologic stage I, and those who smoking or undergoing video-assisted thoracoscopic surgery (VATS) or segmentectomy and lobectomy. CONCLUSIONS: Sublobar resection was associated with significantly better perioperative outcomes without compromising short term survival in elderly patients with clinical stage I NSCLC. However, the importance of patient selection and management process, as well as accurate lymph node staging must be acknowledged when making the surgical decision (clinical registration number: NCT03429673).

[Systemic Therapy for Low-grade Pulmonary Neuroendocrine Tumor].

The lung is the second most common site of neuroendocrine tumors (NETs). Typical and atypical carcinoids are low-grade NETs of the lung. These rare tumors have received little attention and education is needed for treating physicians. The article describes the classifcation of lung NETs, the epidemiology and pathological characteristics. When lung NETs are diagnosed at an early stage, surgical intervention is often curative. For advanced lung NETs patients, different treatment methods including chemotherapy, somatostatin analogs, m-TOR inhibition, peptide receptor radioligand therapy, and biologic systemic therapy are discussed. The conclusions are generally extrapolated from the outcome of extra-pulmonary carcinoids. Prospective randomized well-designed trials are urgently needed to inform current recommendations on systemic treatment.
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Thoracoscopic lobectomy for massive hemoptysis caused by complete pulmonary vein occlusion after radiofrequency ablation for atrial fibrillation.

Complete pulmonary vein occlusion is a rare complication of transcatheter radiofrequency ablation for atrial fibrillation. We here report a 37-year-old man who presented with massive hemoptysis as a result of left superior pulmonary vein occlusion caused by transcatheter radiofrequency ablation for paroxysmal atrial fibrillation. The patient was successfully managed with thoracoscopic left upper lobectomy with a satisfactory outcome.

Serum miR-30c Level Predicted Cardiotoxicity in Non-small Cell Lung Cancer Patients Treated with Bevacizumab.

Cardiotoxicity is a common adverse effect induced by drug chemotherapy. miR-30c has been reported to be involved in the progress of heart diseases. In the present study, miR-30c was used to predict the cardiotoxicity in non-small cell lung cancer (NSCLC) patients treated with bevacizumab chemotherapy. Eighty NSCLC patients were included in this study. Serum miR-30c levels were detected at pre-chemotherapy, during-chemotherapy (the 2nd, 4th, and 8th week) and 1 month after chemotherapy. miR-30c expression was elevated with the duration of the chemotherapy cycle and decreased 1 month after chemotherapy. The correlation analysis showed that serum miR-30c levels were positively related to cardiotoxicity before chemotherapy and during chemotherapy. ROC curve analysis showed the values of AUC, sensitivity, and specificity for the level of miR-30c alteration (from pre-chemotherapy to during-chemotherapy) were 0.851, 0.720, and 0.860, respectively. Serum miR-30c level is elevated during bevacizumab chemotherapy, which is probably an early detection biomarker for predicting cardiotoxicity in NSCLC patients treated with drug chemotherapy.

Carbonic anhydrase 1 is a promising biomarker for early detection of non-small cell lung cancer.

This study aimed to identify candidate biomarkers associated with stage I non-small cell lung cancer (NSCLC). Sera from three groups, a lung cancer group (n = 11), benign control group (n = 12), and normal control group (n = 10), were collected and pooled. Protein expression profiles were analyzed by a combination of two-dimensional electrophoresis (2DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). These methods were used to separate, screen, and identify proteins that were differentially expressed between stage I NSCLC and controls. Differentially expressed proteins were validated by both Western blot and ELISA in an expanded sample size (22, 18, and 18 in three groups, respectively). MALDI-MS identified 12 differentially expressed proteins in the lung cancer group compared to the two control groups. Expression of carbonic anhydrase 1 (CA1) was validated by Western blot. CA1 was significantly elevated in the lung cancer group compared to controls. ELISA results confirmed that CA1 in the lung cancer group (3.18 ± 1.27 ng/mL, n = 22) was highly expressed in stage I NSCLC patients compared to those in the benign control group (2.21 ± 0.71 ng/mL, n = 18) and the normal control group (2.04 ± 0.63 ng/mL, n = 18) (P = 0.001). In conclusion, we provide evidence that CA1 is highly expressed in the sera of stage I NSCLC patients. Additionally, CA1 might serve as a novel biomarker for early detection of NSCLC.

[Clinical analysis of completion pneumonectomy for pulmonary disease].

OBJECTIVE: Completion pneumonectomy (CP) is widely known to be associated with a high morbidity and mortality. However, in certain instances, CP offers the only chance for a cure. Now to explore the indications, prevention and management of complications as well as late outcomes of CP. METHODS: During a period of 21 years from January 1985 to August 2006, 24 patients received CP, representing 2.3% of 1026 patients who had undergone pneumonectomy in the same period. There were 17 right and 7 left CPs done in 20 male and 4 female patients with an average age of 58 years (range from 42 to 67 years). Lung malignancy accounted for 22 of these cases in which the indication included local recurrence in 18, second primary tumors in 2 and primary malignancies that developed after right upper lobectomies for pulmonary tuberculoma and pulmonary cyst respectively in 2 cases. Benign disease was progression or recurrence of bronchiectasis in 2 cases. Before CP, 17 patients had had a lobectomy, 5 a bilobectomy, 1 sleeve lobectomy and 1 wedge resection. There were 16 of 20 lung cancer patients receiving postoperative chemotherapy and 3 with positive residues having radiotherapy. The mean interval between the two procedures was 65 months for the whole group (5.5-360) and 32 months for lung cancer patients (5.5-120). They all underwent CP, included sleeve CP in 1 patient. RESULTS: For all patients, the previous thoracotomy incision was reopened and maneuvers such as rib resection, intrapericardial blood vessel ligation, division of the bronchus first, local application of glues and hemostatic agents, and bronchial reinforcement were routinely used. Intrapericardial route was used in 10 patients (41.7%). Two patients had right pulmonary artery injured. The operation lasted 4-7 hours, with blood loss of 300 to 3000 ml. Overall respectability, morbidity and hospital mortality were 95.8%, 29.2% and 4.2%. No intraoperative deaths occurred. There was 1 early postoperative death after 40 days from adult respiratory distress syndrome. There was no occurrence of bronchopleural fistula, and the 25% associated morbidity rate was a result of bleeding necessitating reexploration in 1 case, chronic empyema in 1 case, arrhythmia in 1 case, anemia in 1 case and fever of unknown reason in 2 cases. Actuarial 1-, 3-, 5-year survival rates from the time of completion pneumonectomy for patients with lung cancer were 77.3%, 50.0% and 29.4%. And 1-, 3-, 5-year survival rates for patients with recurrent lung cancer were 72.2%, 47.1% and 29.4%. CONCLUSIONS: CP can be performed with an acceptable operative mortality and morbidity rate in selected patients. For patients with local recurrence, first and second primary bronchogenic carcinoma as well as benign pulmonary disease, treatment should be surgical when a less invasive procedure is not available and the patients are in good health. In addition, patients undergoing CP have a reasonable prospect for long-term survival.

[Research on cellular immune function of patients with lung cancer before and after operation].

BACKGROUND: To explore the perioperative changes of T subsets and NK cell and analyze the related factors in patients with lung cancer. METHODS: The T subsets and NK cell from peripheral blood of 60 patients with lung cancer, 15 patients with lung benign tumor and 15 healthy people were detected by immunofluorescence. These indexes of the patients with lung cancer were detected also at postoperative 2nd, 7th, 14th and 28th days. RESULTS: 1.There were significant differences in the indexes between the lung cancer group and the groups of lung benign tumor and normal people except for CD8+ (P < 0.05). 2.At postoperative 2nd day CD3+, CD4+, CD4+/CD8+ and NK cell of the patients with lung cancer were decreased and CD8+ was increased significantly than those before operation (P < 0.05). During postoperative 1 to 2 weeks, all indexes had recovered basically to the preoperative level. At postoperative 28th day, CD3+, CD4+ , CD4+/CD8+ and NK cell were increased and CD8+ was decreased than those before operation (P < 0.05). 3. There was significant difference in the indexes among preoperative stage IIIA, IIIB and IB, and between preoperative N2 diseases and N0 group (P < 0.05). There was significant difference between the groups of radical and palliative operation and the group of thoracic exploration at postoperative 28th day (P < 0.05). There was significant difference in T subsets between the groups of blood transfusion and non-transfusion at postoperative 14th day (P < 0.05). CONCLUSIONS: The cellular immune function of the patients with lung cancer was lower than that of the patients with lung benign tumor and normal people. The perioperative immunity of patients with lung cancer decreases after operation and increases later. TNM stage and lymph node metastasis are relative to preoperative but not postoperative immunity. There is no significant correlation between cellular immune function and pathological type of the tumor. Radical and palliative operations can both significantly increase the patients' cellular immune function. Therefore the palliative operation is better than thoracic exploration. Blood transfusion can depress the immune function of the patients, so it is better to avoid perioperative blood transfusion.

[Mediastinoscopy in 165 patients].

OBJECTIVE: To investigate the value of mediastinoscopy in diagnosis of the thoracic diseases and the determination of the operative indication. METHODS: From 1979 to 2000, 165 patients were given mediastinoscopy by local infiltration anesthesia (rare cases with additional vein bacic anesthesia). The exploration and biopsy were given to the neoplasms and lymph nodes around the trachea through the pretracheal interstice. RESULTS: The diagnosis of 125 patients by mediastinoscopy accorded with the pathological diagnosis and that of 21 patients was not accorded with the pathology. The rate of definitive diagnosis was 85.6% (125/146). The other 19 cases were not included into the ground because 11 cases were not given definitive diagnosis and 8 cases with lung cancer were not be performed operation although the results of mediastinoscopy were negative. Twenty patients with lung cancer which had metastasis in the mediastium and 7 patients with malignant lymphadenoma avoided exploratory thoracotomy. CONCLUSION: The mediastinoscopy is a effective examinative method to the disease involving the lymph nodes in the mediastinum and the thoracic disease closing on the mediastinum. The mediastinoscopy in appropriate especially to the simple enlargement of lymph node in the mediastinum that is not given definitive diagnosis. The cases with lung cancer accompanied enlargement of lymph node in the mediastinum and that with tumors in the mediastinum may choose the mediastinoscopy.