Prognostic biomarker discovery based on proteome landscape of Chinese lung adenocarcinoma.

Despite recent innovations in imaging and genomic screening promotes advance in diagnosis and treatment of lung adenocarcinoma (LUAD), there remains high mortality of LUAD and insufficient understanding of LUAD biology. Our previous study performed an integrative multi-omic analysis of LUAD, filling the gap between genomic alterations and their biological proteome effects. However, more detailed molecular characterization and biomarker resources at proteome level still need to be uncovered. In this study, a quantitative proteomic experiment of patient-derived benign lung disease samples was carried out. After that, we integrated the proteomic data with previous dataset of 103 paired LUAD samples. We depicted the proteomic differences between non-cancerous and tumor samples and among diverse pathological subtypes. We also found that up-regulated mitophagy was a significant characteristic of early-stage LUAD. Additionally, our integrative analysis filtered out 75 potential prognostic biomarkers and validated two of them in an independent LUAD serum cohort. This study provided insights for improved understanding proteome abnormalities of LUAD and the novel prognostic biomarker discovery offered an opportunity for LUAD precise management.

Elevated tumor markers in a benign lung disease.

BACKGROUND: This study aimed to determine the underlying pathophysiologic mechanism of elevated carbohydrate antigen 19-9 (CA19-9) in pulmonary sequestration (PS) patients. MATERIALS AND METHODS: Four pulmonary sequestration patients, 12 pneumonia patients and 12 healthy adult volunteers were prospectively studied. Specimens from another 34 pulmonary sequestration patients were retrospectively analyzed. Serum CA19-9 levels of 4 patients were tested before and 1 week, 1 month and 3 months after surgery. The CA19-9 levels of 12 pneumonia patients and 12 healthy adult volunteers were tested as controls. The expression and localization of CA19-9 in diseased lesions and corresponding normal lung tissues were analyzed by Immunohistochemical (IHC). Hematoxylin-eosin (HE) staining was performed to observe the pathological changes in pulmonary sequestration tissues. RESULTS: Serum CA19-9 levels were significantly higher in the 4 patients (797.3 ± 316 IU/ml) than in the pneumonia patients (10.07 ± 5.01 IU/ml) and healthy volunteers (9.85 ± 4.12 IU/ml). In addition, serum CA19-9 levels decreased dramatically after the focus was removed. Positive staining of CA19-9 was found in 70% (24/34) of pulmonary sequestration tissues, and CA19-9 was mainly expressed in the bronchial mucus. In the 4 diseased lesions, deformed alveolar structure and inflammatory cell infiltration were observed, and the degree of damage was positively correlated with serum CA19-9 levels. CONCLUSIONS: CA19-9 could be generated by abnormal columnar epithelia in pulmonary sequestration tissues and was transported into circulation after alveoli damage. CA19-9 could serve as an adjuvant diagnostic marker in pulmonary sequestration.

Surgery for hemoptysis in patients with benign lung disease.

BACKGROUND: Hemoptysis can be a life-threatening condition that requires urgent treatment. Surgery still plays an important role in managing this critical situation, although previous reports have reported high postoperative morbidity and mortality rates. We report our experience with surgical resection for hemoptysis caused by benign lung diseases. METHODS: We reviewed the retrospectively collected data from 94 patients undergoing pulmonary resection for various benign lung diseases with hemoptysis at a single institution from 2010 to 2016. Baseline characteristics, surgical factors, and postoperative outcomes (morbidity and mortality rates) were analyzed. RESULTS: The ratio of male to female patients was 1:1, and the mean age was 58.2±11.1 (range, 29-79) years. The etiology of hemoptysis included aspergilloma in 58 patients (61.7%), bronchiectasis in 10, tuberculosis in 7, necrotizing bronchiolitis in 6, and other inflammatory disease in 13. A total of 21 patients (22.3%) underwent emergency operation, and 73 (77.7%) had an elective operation. Pulmonary resection was performed by thoracotomy (n=53, 56.4%) and video-assisted thoracoscopic surgery (VATS) (n=41, 43.6%). Sublobar resection (n=50, 53.2%, segmentectomy in 19 and wedge resection in 31) was performed more often than lobectomy (n=35, 37.2%). Pneumonectomy was performed in 7 patients, and bilobectomy was performed in 2. Postoperative morbidity occurred in 23 patients (24.5%), with prolonged air leak being the most frequent complication (n=14, 14.9%). The in-hospital mortality rate was 3.2% (n=3). Complications were less frequent in patients undergoing an elective operation, VATS, and sublobar resection. Multivariate analysis showed that patients treated with VATS had a decreased risk of postoperative complications (odds ratio, 12.8; 95% confidence interval, 1.29-127.9; P=0.03). CONCLUSIONS: Surgical resection for hemoptysis in patients with benign lung diseases is the mainstay of effective treatment with acceptable morbidity and mortality rates. If applicable, we recommend elective (planned) sublobar resection using VATS in order to improve postoperative outcomes.

Characteristics of benign lung diseases mimicking lung cancer in preoperative CT of 173 patients / 中国胸心血管外科临床杂志

@#Objective To improve accuracy of clinical diagnosis through analyzing the CT characteristics and clinical manifestations of patients with benign lung diseases whose CT manifestations initially led to a suspicion of lung cancer. Methods This study collected 2 239 patients of benign lung disease verified by postoperative pathology in the Department of Thoracic Surgery, Beijing Chao-yang Hospital from June 2006 to December 2016. Lesions of 173 patients (101 males and 72 females with a mean age of 56.0 years) were considered very likely to be malignant on preoperative contrast CT scan, which were sorted to 20 types of lung diseases, and the 20 types of diseases contained 907 patients diagnosed or misdiagnosed. Statistical analyses were performed using the CT and clinical characteristics of the 173 patients. Results Among the 907 patients with benign lung disease, the benign pathologies that were most commonly misdiagnosed by preoperative enhanced CT were pulmonary leiomyoma (100.0%), pulmonary actinomycosis (75.0%), pulmonary cryptococcosis (71.4%), sclerosing hemangioma (50.0%) and organizing pneumonia (44.2%). Among the 173 patients with benign diseases, the most common diseases were tuberculosis (29.5%), organizing pneumonia (28.9%), pulmonary hamartoma (6.4%) and pulmonary abscess (6.4%). In the 173 patients, 17.3% had fever, 56.6% coughing, 8.7% yellow sputum, 28.9% hemoptysis, 16.2% chest pain, 18.5% elevated leukocyte counts and 4.6% elevated carcinoembryonic antigen levels. Most of the CT manifestations consisted of nodular or mass shadows, 70.5% of which had foci≤3 cm and manifestations were similar to those of lung cancer, such as a spiculated margin (49.1%), lobulation (33.5%), pleural indentation (27.2%) and significant enhancement (39.3%). Furthermore, some patients had uncommon tumor signs, such as calcification (12.7%), central liquefactive necrosis (18.5%), satellite foci (9.8%) and multiple pulmonary nodules (42.2%). Moreover, 24.3% of the patients had enlarged lymph nodes of the mediastinum or hilum. Conclusion As the CT manifestations of some benign lung conditions are similar to those of lung cancer, careful differential diagnosis is necessary to identify the basic characteristics of the disease when the imaging results are ambiguous, and the diagnosis of a lung disease need incorporate the patients' clinical characteristics and a comprehensive analysis.

Comparison of uniportal and three portal video-assisted thoracic surgery in benign pulmonary diseases / 实用医学杂志

Objective To compare the advantages and disadvantages of uniportal video-assisted thoracic surgery(uniportal-VATS)and three portal VATS in treatment of benign pulmonary diseases. Methods The clinical data of 66 patients with benign pulmonary disease treated by VAST from June 2015 to October 2016 were retrospec-tively analyzed. The patients were divided into two groups according to the specific operation. There were 32 patients (18 males and 14 females)in uniportal-VATS group. There were 34 patients(18 males and 16 females)in three portal VATS group. The operative time ,intraoperative blood loss ,thoracic drainage volume at 24 h after opera-tion,incision length,and the time of postoperative drainage of thoracic cavity,postoperative third day pain score and complication rate were compared between the two groups. Results The patients in the experimental and the control groups were successfully operated according to the scheduled protocol. No thoracotomy was performed. There was no statistical difference in the volume of blood loss,the volume of pleural drainage after 24 hours,the time of postoperative drainage of thoracic cavity ,the length of hospital stays and postoperative complications in uni-portal-VATS group and three portal VATS group(P>0.05). The pain score and postoperative third day pain score of the uniportal-VATS group was better than that of the three portal VATS group(P<0.05),but the operation time of the uniportal-VATS group was longer than that of the three portal VATS group(P<0.05). Conclusion Uniportal-VATS is safe and feasible for the treatment of benign lung diseases. It is more minimally invasive and beautiful than traditional three-hole thoracoscopic surgery. It is worthy of promotion and has broad prospects.

Diagnostic value of Cyfra21-1, SCC and CEA for differentiation of early-stage NSCLC from benign lung disease.

Non-small cell lung cancer (NSCLC), which account for the most of lung carcinoma, is sometimes difficult to differentiate from benign lung diseases presented with nodular shadow in imaging scan. There is a need to find another non-invasive way to diagnosis early-stage NSCLC. To examine the potential diagnostic value of SCC, CFYRA 21-1 and CEA for the differentiation of early-stage NCSCL from benign lung diseases, we analyzed serum levels of tumor markers in 278 patients, including 248 patients with NSCLC and 30 patients with benign lung diseases. These benign lung diseases were presented with evidence of a high likelihood of having lung cancer. After surgical operation, diagnosis of lung cancer and benign lung disease were confirmed by histological examination. Preoperative tumor marker levels were quantified. Mann-Whitney U test was used to compare median levels of SCC, CFYRA 21-1 and CEA between the benign group and lung cancer group. Analysis of variance results were used for differences between different clinical stages of NSCLC. ROC was used to evaluate the diagnostic value of tumor markers. The median levels of Cyfra21-1, SCC and CEA were much higher in NSCLC than those in benign lung diseases. And we found that the mean levels of tumor marker were higher in advanced stage of NSCLC. The combination of tumor markers resulted in a higher sensitivity (91.3%) and a lower specificity (86.7%). In conclusion, the combination of positive SCC, positive CEA and positive Cyfra21-1 appear to be helpful in distinguishing early-stage NSCLC from benign lung disease which presented with suspicious pulmonary masses.

LUNX mRNA-positive cells at different time points predict prognosis in patients with surgically resected nonsmall cell lung cancer.

LUNX is a lung-specific gene whose messenger ribonucleic acid (mRNA) expression is strictly limited to normal lung tissue and nonsmall cell lung cancer (NSCLC) tissue. The aim of this study was to investigate whether the detection of LUNX mRNA-positive circulating tumor cells (CTC)s in peripheral blood at different time points is useful for predicting disease recurrence, disease-free survival (DFS), and overall survival (OS) in NSCLC patients undergoing surgery. Serial blood samples from 68 patients with stage I-IIIA NSCLC were examined by real-time quantitative polymerase chain reaction assay targeting LUNX mRNA before (T0) and after surgery (T1) and after the completion of adjuvant chemotherapy (T2). Results showed that LUNX mRNA-positive CTCs were detected in 40 of 68 NSCLC patients (58.8%) before surgery; the detection rates of LUNX mRNA-positive CTCs at T1 and T2 time points were 32.4% (22/68) and 33.3% (20/60), respectively. The detection of LUNX mRNA-positive CTC at 3 time points was associated with lymph node status and pathologic stage. During the follow-up period, patients with LUXN mRNA-positive CTC at 3 time points had a higher relapse rate and a shorter DFS and OS than those without. Multivariate analysis revealed that presence of LUNX mRNA-positive CTC at T1 and T2 time points was an independent unfavorable factor for DFS and OS. In conclusion, detection of LUNX mRNA-positive CTC after surgery and the completion of adjuvant chemotherapy in patients with stage I-IIIA NSCLC are highly predictive for DFS and OS. This technique could aid in the prediction of prognosis and design of tailored treatment.