Integrative Proteomic Characterization of Human Lung Adenocarcinoma.

Genomic studies of lung adenocarcinoma (LUAD) have advanced our understanding of the disease's biology and accelerated targeted therapy. However, the proteomic characteristics of LUAD remain poorly understood. We carried out a comprehensive proteomics analysis of 103 cases of LUAD in Chinese patients. Integrative analysis of proteome, phosphoproteome, transcriptome, and whole-exome sequencing data revealed cancer-associated characteristics, such as tumor-associated protein variants, distinct proteomics features, and clinical outcomes in patients at an early stage or with EGFR and TP53 mutations. Proteome-based stratification of LUAD revealed three subtypes (S-I, S-II, and S-III) related to different clinical and molecular features. Further, we nominated potential drug targets and validated the plasma protein level of HSP 90ß as a potential prognostic biomarker for LUAD in an independent cohort. Our integrative proteomics analysis enables a more comprehensive understanding of the molecular landscape of LUAD and offers an opportunity for more precise diagnosis and treatment.

Successful resolution of ectopic Cushing syndrome by minimally invasive thoracoscopic resection of the neuroendocrine tumor of the thymus: a rare case report.

BACKGROUND: Ectopic Cushing syndrome (ECS) is a sporadic condition. Even uncommon is an ECS that derives from a carcinoid tumor of the thymus. These tumors may pose several diagnostic and therapeutic conundrums. This report discusses the differential diagnosis, clinicopathological findings, and effective treatment of a rare case of ECS using a minimally invasive approach. CASE PRESENTATION: A 29-year-old woman with Cushing syndrome presented with facial flushing. Physical examination revealed hypertension (blood pressure: 141/100 mmHg). A mediastinal tumor was discovered to be the cause of the patient's chronic hypokalemia and hypercortisolemia. Cortisol levels increased in the morning, reaching 47.7 ug/dL. The levels of the hormones ACTH, aldosterone, and renin were determined to be 281 pg/mL, 3.0 ng/dL, and 2.1 pg/mL, respectively. The presence of hypertension, hypokalemia, and alkalinity suggested Cushing's syndrome, which was proven to be ACTH-dependent ECS by a dexamethasone suppression test. A chest CT scan revealed inflammation in the posterior basal region of the right lower lobe. The superior anterior mediastinum was characterized by round-shaped isodensity lesions with distinct borders. She underwent thoracoscopic anterior mediastinal tumor excision via the subxiphoid technique (R0 resection); following surgery, her blood pressure returned to normal, and the hypernatremia/hypopotassemia resolved. The tumor was determined to be a thymic carcinoid. Most notably, cortisol levels fell to half of their presurgical levels after one hour of surgery, and other abnormalities corrected substantially postoperatively. CONCLUSION: Thoracoscopic excision of thymic tumors by subxiphoid incision may be a useful treatment option for ECS caused by neuroendocrine tumors of the thymus.

SP1 induced long non-coding RNA LINC00958 overexpression facilitate cell proliferation, migration and invasion in lung adenocarcinoma via mediating miR-625-5p/CPSF7 axis.

BACKGROUND: Increasing evidences have underlined the importance of long non-coding RNAs (lncRNAs) in human malignancies. LINC00958 has been found involved in some cancers. However, the underlying mechanical performance of LINC00958 in lung adenocarcinoma (LAD) has not been explored yet. METHODS: The expression of relevant mRNA and protein were measured by qRT-PCR and western blot assays. EdU, colony formation, TUNEL and transwell assays were performed to investigate the function of LINC00958 on LAD progression. Luciferase reporter, RNA pull down and RIP assays were conducted to investigate the molecular mechanism of relevant RNAs. RESULTS: LINC00958 was found notably overexpressed in LAD, which was associated with the stimulation of its promoter activity induced by SP1. LINC00958 depletion dramatically inhibited LAD cell proliferation, migration and invasion capacities by acting as a miR-625-5p sponge. MiR-625-5p curbed LAD progression via targeting CPSF7 and down-regulating its expression. Mechanically, LINC00958 was identified as a competing endogenous RNA (ceRNA) and positively regulated the expression of CPSF7 via sponging miR-625-5p. CONCLUSIONS: LINC00958 might drive LAD progression via mediating miR-625-5p/CPSF7 axis, indicating the potential of targeting LINC00958 for the treatment of LAD.

Trace metals in resuspended fraction of settled bus dust and assessment of non-occupational exposure.

Trace metals (TMs) within urban public transportation systems have rarely been studied and information on related health risks is scant. This study measured TM (arsenic, chromium, cadmium, nickel, zinc, copper and lead) concentrations in resuspended fractions of settled bus dust in Harbin, China, and estimated the exposure and health risks. The incremental lifetime cancer risk (ILCR) for commuters was estimated for TM exposures. The average concentration of total TMs was 559µg/g (ranges from 312 to 787) among 45 bus routes in Harbin. The hazard quotient of three selected commuter groups increased in the following order: teenagersdermal contact>inhalation.

[Clinical analyses of surgical treatment for lung metastatic tumors].

OBJECTIVE: To evaluate the distribution, diagnosis, indication and modus operandi of surgical treatment and prognostic factors for patients with lung metastatic tumors. METHODS: The clinical features were collected for 329 surgical patients with lung metastatic tumors during March 1998 and December 2013. Survival analysis was also performed by Log-rank test and Cox-regression analysis. RESULTS: The origins were epithelial tissue tumors (n = 278), sarcomas (n = 32), germ cell tumors (n = 3), malignant melanoma (n = 3) and miscellaneous tumors (n = 13). Their 1, 3 and 5-year survival rates were 85.1％, 50.9％ and 37.1％ respectively with a median survival time of 38 months. Log-rank survival analysis showed that resection extent (P = 0.004), lymph node dissection (P = 0.017) and radical operation (P < 0.01) were significantly associated with patient survival. And multi-variable Cox-regression analysis showed that lymph node dissection and radical operation were two independent prognostic factors. CONCLUSION: For lung metastatic tumor patients with well-controlled primary malignancy and non-metastasis of other organs, radical resection should be performed with minimal resection extent. And routine systematic lymph node dissection is not recommended. The necessity of lymph node dissection should be determined by radiological evaluations and surgical explorations.

Secretomes are a potential source of molecular targets for cancer therapies and indicate that APOE is a candidate biomarker for lung adenocarcinoma metastasis.

Identifying patients at high risk of metastasis is a major challenge in lung adenocarcinoma (ADC) therapy, therefore discovery of noninvasive biomarkers and therapeutic targets is urgent. We found significant differences between the secretomes of differentially expressed proteins in lung ADC cell lines, clinical tissue samples and serum plasma samples with high and low metastatic potential. In particular, Apolipoprotein E (APOE) levels were three-times greater in cells with lymph node metastases (LNM) than those without. Our study indicates that APOE is a potential indicator of metastatic lung ADC and that secretomes may offer a valuable resource for biomarkers of lung ADC with LNM.

[OLC1 protein levels in plasma of patients with non-small cell lung cancer and its clinical application].

OBJECTIVE: The aim of this study was to detect the plasma concentration of OLC1 (overexpressed in lung cancer 1) protein as a potential cancer biomarker, and evaluating its clinical application value in the diagnosis of non-small cell lung cancer (NSCLC). METHODS: We prepared OLC1 antibody with OLC1 full length protein, in 5-6-week old Bal B/c mice. Each mouse was immunized four times at a dose of 15-30 µg antigen protein, and the interval between two consecutive immunizations was two weeks. Antibody screening was made by ELISA and Western blot, and a double antibody sandwich ELISA kit was developed. We used this established ELISA kit to detect the plasma concentration of OLC1 protein in 281 NSCLC patients and 92 gender- and age-matched healthy controls. Area under the receiver operating characteristic curve (AUC) was used to evaluate the detection efficacy of OLC1. RESULTS: We obtained 11 OLC1 monoclonal antibodies and successfully established the ELISA kit to detect the plasma concentration of OLC1 with a detection range from 1.95 ng/ml to 62.50 ng/ml. OLC1 concentration in the case group (124.69 ng/ml) was significantly higher than that in the control group (67.07 ng/ml, P < 0.001). In the scenario of distinguishing NSCLC from control group, AUC result was 0.69. When the cut-off was set at 67.72 ng/ml, the sensitivity and specificity was 84.4% and 51.1%, respectively. In term of distinguishing early lung cancer (IA) from normal controls, the AUC, sensitivity and specificity were 0.68, 77.8% and 54.4%, respectively. CONCLUSION: The plasma concentration of OLC1 protein is significantly elevated in NSCLC patients. OLC1 may be as a potential cancer biomarker applied in clinical diagnosis.

[Study on 21 cases of multiple primary lung cancer].

OBJECTIVE: To explore the clinical characteristics of multiple primary lung cancer (MPLC) and provide potential clues to the early diagnosis and treatment selection of MPLC patients. METHODS: The clinical data of 21 patients with MPLC confirmed by postoperative histopathology were analyzed retrospectively. RESULTS: All the 21 patients received surgery (pulmonary lobectomy or pulmonary wedge resection), and 49 intrapulmonary tumors were resected. The histopathological examination demonstrated that all the 21 cases were MPLC. Among the 21 patients, 10 had bilateral lesions in lung and 11 had unilateral lesions; 17 suffered synchronous and 4 suffered metachronous tumors; 14 had double two primary tumors, 6 had three primary tumors and 1 had four primary tumors. In these patients, 2 had various histological subtypes among their multiple lesions and 19 had same histological subtypes among their multiple tumors; 14 cases with stage I disease, stage II 2 cases, stage III 5 cases. CONCLUSIONS: For the patients who were detected as MPLC by diagnostic imaging examination, more positive therapeutic decision, such as surgery, could be suggested. The molecular markers should be developed for assisting diagnosis of MPLC.

Single-crystalline Mg-substituted Na4Mn3(PO4)2P2O7 nanoparticles as a high capacity and superior cycling cathode for sodium-ion batteries.

Mn-based mixed phosphate Na4Mn3(PO4)2(P2O7) (NMPP) is a promising cathode for high-potential, low-cost and eco-friendly sodium-ion batteries. However, this material still faces some bottleneck issues in terms of low conductivity, disturbance of impure crystalline phase, micron-sized agglomerated particles and the Mn3+ Jahn-Teller effect. Herein, a Mg-substituted NMPP (NM2.7Mg0.3PP)@C composite was constructed via modified solution combustion and subsequent calcination treatment. The obtained NM2.7Mg0.3PP presents a highly pure phase and single-crystalline characteristics. It is noteworthy that the sample shows a smaller particle size of 100-300 nm due to the Mg2+ incorporation, and the prepared NM2.7Mg0.3PP@C cathode exhibits considerable discharge capacity (119 mA h g-1), an improved rate capability and excellent long cycling stability of 1000 cycles. A series of measurements indicated that the Mg-substitution enhanced the electronic conductivity and ion diffusion rate, and effectively relieved the lattice distortion influenced by the multiphase transition from the Mn Jahn-Teller effect of the NM2.7Mg0.3PP@C cathode. In addition, NM2.7Mg0.3PP adopts an optimal 3Mg0.1-Mn1-Mn2-Mn3 crystal structure based on density functional theory (DFT) calculations and refined X-ray diffractometry results. These findings provide new insight into the design of highly stabilized and high-conductivity polyanionic cathodes for sodium-ion batteries.

Proteomic and Phosphoproteomic Maps of Lung Squamous Cell Carcinoma From Chinese Patients.

Lung squamous cell carcinoma (LUSC) is one of the leading causes of tumor-driven deaths in the world. To date, studies on the tumor heterogeneity of LUSC at genomic level have only revealed limited therapeutic benefits. Therefore, system-wide research of LUSC at proteomic level may further improve precision medicine strategies on individual demands. To this end, we performed proteomic and phosphoproteomic study for LUSC samples of 25 Chinese patients. From our results, two subgroups (Cluster I and II) based on proteomic data were identified, which were associated with distinct molecular characteristics and clinicopathologic features. Combined with phosphoproteomic data, our result showed that spliceosome pathway was enriched in Cluster I, while focal adhesion pathway, immune-related pathways and Ras signaling pathway were enriched in Cluster II. In addition, we found that lymph node metastasis (LNM) was associated with our proteomic subgroups and cell cycle pathway was enriched in patients with LNM. Further analysis showed that MCM2, a DNA replication licensing factor involved in cell cycle pathway, was highly expressed in patients with poor prognosis, which was further proved by immunohistochemistry (IHC) analysis. In summary, our study provided a resource of the proteomic and phosphoproteomic features of LUSC in Chinese patients.

[Clinical data analysis on 43 cases of the giant lymph node hyperplasia].

OBJECTIVE: To summarize the clinical features, treatment and prognosis of giant lymph node hyperplasia (Castleman's disease, CD). METHODS: The clinical data of 43 CD patients with the tumor located in neck (n = 10), chest (n = 20), abdomen (n = 9) and multi-centers (n = 4) were analyzed. RESULTS: All the patients underwent surgical resection of tumor or lymph and the patients of multicentric disease underwent adjuvant chemotherapy or radiotherapy. All the diagnoses of CD were confirmed by pathological examination. Among all the cases, 26 patients were hyaline vascular subtype (HV), 16 patients plasma cell subtype (PC) and 1 patient mixed subtype. All 39 patients of unicentric disease survived without disease evidence. 2 patients of multicentric disease died at 18 months and 54 months after surgery; 1 patient survived with disease; 1 patient survived with no evidence of disease. CONCLUSION: Giant lymph node hyperplasia is a rare disease. The diagnosis depends mainly on the pathological examination. Surgery is the best choice for unicentric disease with an excellent prognosis. Patients with multicentric disease may benefit from surgery, adjuvant chemotherapy or radiotherapy, but the prognosis remains grim.

Surgical Treatment of Tracheal Lipoma after Multiple Bronchoscopy Interventions and Placements of a Tracheal Stent.

Background The majority of adult primary tracheal tumors are malignant; however, as one type of benign tumors, lipoma is extremely uncommon. Case Description We report a case where lipoma was first misdiagnosed as bronchial asthma, followed by sudden aggravation of dyspnea after trauma, and computed tomography (CT) examination of the neck and chest confirmed a tracheal tumor. Through multiple bronchoscopy interventions and placements of a tracheal stent, little therapeutic benefit was discovered, and resection of the tracheal tumor combined with tracheal end-to-end anastomosis was performed to ultimately achieve a cure. Conclusion Primary tracheal tumors should be highly suspected in patients with recurrent and gradually worsening dyspnea; timely cervical, thoracic CT and bronchoscopy can provide an accurate diagnosis. Surgical radical resection is the only way to cure all benign tracheal tumors such as lipoma.

Carbon emissions tax policy of urban road traffic and its application in Panjin, China.

How to effectively solve traffic congestion and transportation pollution in urban development is a main research emphasis for transportation management agencies. A carbon emissions tax can affect travelers' generalized costs and will lead to changes in passenger demand, mode choice and traffic flow equilibrium in road networks, which are of significance in green travel and low-carbon transportation management. This paper first established a mesoscopic model to calculate the carbon emissions tax and determined the value of this charge in China, which was based on road traffic flow, vehicle speed, and carbon emissions. Referring to existing research results to calibrate the value of time, this paper modified the traveler's generalized cost function, including the carbon emissions tax, fuel surcharge and travel time cost, which can be used in the travel impedance model with the consideration of the carbon emissions tax. Then, a method for analyzing urban road network traffic flow distribution was put forward, and a joint traffic distribution model was established, which considered the relationship between private cars and taxis. Finally, this paper took the city of Panjin as an example to analyze the road traffic carbon emissions tax's impact. The results illustrated that the carbon emissions tax has a positive effect on road network flow equilibrium and carbon emission reduction. This paper will have good reference value and practical significance for the calculation and implementation of urban traffic carbon emissions taxes in China.

Genomic heterogeneity of multiple synchronous lung cancer.

Multiple synchronous lung cancers (MSLCs) present a clinical dilemma as to whether individual tumours represent intrapulmonary metastases or independent tumours. In this study we analyse genomic profiles of 15 lung adenocarcinomas and one regional lymph node metastasis from 6 patients with MSLC. All 15 lung tumours demonstrate distinct genomic profiles, suggesting all are independent primary tumours, which are consistent with comprehensive histopathological assessment in 5 of the 6 patients. Lung tumours of the same individuals are no more similar to each other than are lung adenocarcinomas of different patients from TCGA cohort matched for tumour size and smoking status. Several known cancer-associated genes have different mutations in different tumours from the same patients. These findings suggest that in the context of identical constitutional genetic background and environmental exposure, different lung cancers in the same individual may have distinct genomic profiles and can be driven by distinct molecular events.

Endotracheal and endobronchial metastases in a patient with stage I lung adenocarcinoma.

Endotracheal or endobronchial metastasis from primary lung cancer is extremely rare. We report a case of endotracheal and endobronchial metastases from peripheral early lung adenocarcinoma 7 months after complete resection. The patient harbored the same gene mutation in both primary and metastatic lesions. This report highlights that enough attention on endotracheal metastases should be paid no matter what the pathologic TNM stage of primary lung cancer is.

A retrospective study of unicentric and multicentric Castleman's disease: a report of 52 patients.

Castleman's disease (CD) is a rare disorder characterized by non-cancerous tumor growth that may develop in the lymph node tissue at a single site or throughout the body (Castleman et al. in Cancer 9:822-830, 1956). It involves hyperproliferation of specific B cells that produce the cytokine IL-6. This disorder is often undiagnosed or misdiagnosed. For this reason, only very few patients have been reported, and little information is available in the literature. In hopes of providing a better understanding of this rare disease, this report examines 52 patients with Unicentric Castleman's disease (UCD) and Multicentric Castleman's disease (MCD) treated from 1999-2008 at a single institution. Fifty-two patients with CD, along with their histological diagnoses, were collected. Patients were divided into two groups--the more common UCD and the less common MCD. Relevant clinical, pathological, and laboratory data were examined in order to evaluate treatment responses, with symptom onsets and survival period serving as the endpoints of the assessment. Each of the 48 patients with UCD exhibited benign symptoms and underwent a curative surgical resection with excellent prognosis. All of the four patients with MCD received surgical resection. Three of the four patients relapsed and received radiotherapy and/or chemotherapy. Only one of the three post-treatment patients survived. UCD is manifested in the form of benign, painless, slow lymph node enlargement that is generally asymptomatic. Complete surgical removal is recommended as a course of curative treatment. The multicentric form of CD exhibits a progressive clinical course with potential for malignancy. There is currently no standard therapy for MCD.

Multiple organ metastases of Pulmonary Epithelioid Haemangioendothelioma and a review of the literature.

This report describes a case of pulmonary epithelioid haemangioendothelioma presented as multi-organ metastases including lung, liver and bone in a 56-year-old woman with an initial diagnosis made with thoracoscopic wedge biopsy. The diagnosis is confirmed through immunohistochemistry. This is a rare disease, with approximately 90 cases described in the English literature and approximately 10 cases reported in China. The case of PEH presented as multiple pulmonary nodules and metastasing to liver and bone is rare in the English literature. The rarity of this condition, the lack of clear standards for treatment, and the partial-to-complete spontaneous regression of EHE seen in some patients up to 15 years from initial detection makes it difficult to decide on the most appropriate treatment. This report may contribute to the data on clinical findings and natural history of this rare tumor.

[Feasibility of thoracoscopic pulmonary metastasectomy].

BACKGROUND & OBJECTIVE: With the developments in endoscopic surgery and the advances of radiological techniques, thoracoscopic pulmonary metastasectomy has been used more and more widely. This study was to evaluate the feasibility of thoracoscopic resection of pulmonary metastases. METHODS: The clinical data of 17 patients who underwent thoracoscopic pulmonary metastasectomy were retrospectively analyzed. RESULTS: All pulmonary metastases in the 17 patients were peripherally located and encountered during follow-up after treatment of primary disease. Metastases at other sites were excluded. Among the 17 cases of metastases, 10 were solitary metastasis, 4 were unilateral multiple metastases, 3 were bilateral metastases. All patients underwent thoracoscopic wedge resection. No major complications, operative mortality, and port site metastasis presented. Postoperative locoregional relapse occurred in 5 patients, in which 4 patients had multiple metastases, the rest 1 patient with soft tissue sarcoma underwent a second thoracoscopic resection of recurrent pulmonary lesion. The 1-, 3-, and 5-year survival rates were 77.3%, 53.1%, and 34.8%, respectively. CONCLUSIONS: Thoracoscopic resection is feasible and effective for patients with a solitary pulmonary metastasis, especially when the lesion is smaller than 3 cm and peripherally located. Bilateral pulmonary metastases may also be resected by primary thoracoscopic operation.