Immune cell infiltration is of great significance for the diagnosis and prognosis of cancer. In this study, we collected gene expression data of non-small cell lung cancer (NSCLC) and normal tissues included in TCGA database, obtained the proportion of 22 immune cells by CIBERSORT tool, and then evaluated the infiltration of immune cells. Subsequently, based on the proportion of 22 immune cells, a classification model of NSCLC tissues and normal tissues was constructed using machine learning methods. The AUC, sensitivity and specificity of classification model built by random forest algorithm reached 0.987, 0.98 and 0.84, respectively. In addition, the AUC, sensitivity and specificity of classification model of lung adenocarcinoma and lung squamous carcinoma tissues constructed by random forest method 0.827, 0.75 and 0.77, respectively. Finally, we constructed a prognosis model of NSCLC by combining the immunocyte score composed of 8 strongly correlated features of 22 immunocyte features screened by LASSO regression with clinical features. After evaluation and verification, C-index reached 0.71 and the calibration curves of three years and five years were well fitted in the prognosis model, which could accurately predict the degree of prognostic risk. This study aims to provide a new strategy for the diagnosis and prognosis of NSCLC based on the classification model and prognosis model established by immune cell infiltration.
Algorithms ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; physiopathology ; Humans ; Lung Neoplasms ; diagnosis ; physiopathology ; Machine Learning ; Prognosis

Lung cancer is the leading cause of cancer-related deaths worldwide. Recently, advancements in our ability to identify and study stem cell populations in the lung have helped researchers to elucidate the central role that cells with stem cell-like properties may have in lung tumorigenesis. Much of this research has focused on the use of the airway repair model to study response to injury. In this review, we discuss the primary evidence of the role that cancer stem cells play in lung cancer development. The implications of a stem cell origin of lung cancer are reviewed, and the importance of ongoing research to identify novel therapeutic and prognostic targets is reiterated.
Animals ; Carcinoma, Non-Small-Cell Lung ; pathology ; Cell Transformation, Neoplastic ; Humans ; Lung Injury ; physiopathology ; Lung Neoplasms ; pathology ; Neoplastic Stem Cells ; pathology ; Regeneration

OBJECTIVE: To estimate a new technique for quantifying regional lung motion using 3D-MRI in healthy volunteers and to apply the technique in patients with intra- or extrapulmonary tumors. MATERIALS AND METHODS: Intraparenchymal lung motion during a whole breathing cycle was quantified in 30 healthy volunteers using 3D-dynamic MRI (FLASH [fast low angle shot] 3D, TRICKS [time-resolved interpolated contrast kinetics]). Qualitative and quantitative vector color maps and cumulative histograms were performed using an introduced semiautomatic algorithm. An analysis of lung motion was performed and correlated with an established 2D-MRI technique for verification. As a proof of concept, the technique was applied in five patients with non-small cell lung cancer (NSCLC) and 5 patients with malignant pleural mesothelioma (MPM). RESULTS: The correlation between intraparenchymal lung motion of the basal lung parts and the 2D-MRI technique was significant (r = 0.89, p < 0.05). Also, the vector color maps quantitatively illustrated regional lung motion in all healthy volunteers. No differences were observed between both hemithoraces, which was verified by cumulative histograms. The patients with NSCLC showed a local lack of lung motion in the area of the tumor. In the patients with MPM, there was global diminished motion of the tumor bearing hemithorax, which improved siginificantly after chemotherapy (CHT) (assessed by the 2D- and 3D-techniques) (p < 0.01). Using global spirometry, an improvement could also be shown (vital capacity 2.9 +/- 0.5 versus 3.4 L +/- 0.6, FEV1 0.9 +/- 0.2 versus 1.4 +/- 0.2 L) after CHT, but this improvement was not significant. CONCLUSION: A 3D-dynamic MRI is able to quantify intraparenchymal lung motion. Local and global parenchymal pathologies can be precisely located and might be a new tool used to quantify even slight changes in lung motion (e.g. in therapy monitoring, follow-up studies or even benign lung diseases).
Carcinoma, Non-Small-Cell Lung/*physiopathology ; Case-Control Studies ; Female ; Humans ; Image Processing, Computer-Assisted ; *Imaging, Three-Dimensional ; Lung Neoplasms/*physiopathology ; Magnetic Resonance Imaging/*methods ; Male ; Mesothelioma/*physiopathology ; Middle Aged ; Movement/*physiology

PURPOSE: To investigate associations between dyspnea and clinical outcomes in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: From 2001 to 2014, we retrospectively reviewed the prospective lung cancer database of St. Paul's Hospital at the Catholic University of Korea. We enrolled patients with NSCLC and evaluated symptoms of dyspnea using modified Medical Research Council (mMRC) scores. Also, we estimated pulmonary functions and analyzed survival data. RESULTS: In total, 457 NSCLC patients were enrolled, and 259 (56.7%) had dyspnea. Among those with dyspnea and whose mMRC scores were available (109 patients had no mMRC score), 85 (56.6%) patients had an mMRC score <2, while 65 (43.3%) had an mMRC score ≥2. Significant decreased pulmonary functions were observed in patients with dyspnea. In multivariate analysis, aging, poor performance status, advanced stage, low forced expiratory volume in 1 second (%), and an mMRC score ≥2 were found to be significant prognostic factors for patient survival. CONCLUSION: Dyspnea could be a significant prognostic factor in patients with NSCLC.
Aged ; Carcinoma, Non-Small-Cell Lung/complications/pathology/*physiopathology ; Dyspnea/*etiology/*physiopathology ; Female ; Forced Expiratory Volume ; Humans ; Lung Neoplasms/complications/pathology/*physiopathology ; Male ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Severity of Illness Index

BACKGROUND: Lung cancer and chronic obstructive pulmonary disease (COPD) are both common diseases in respiratory system and the leading causes of deaths worldwide. The purpose of this study was to determine whether the severity of COPD affects long-term survival in non-small cell lung cancer (NSCLC) patients after surgical resection. METHODS: A retrospective research was performed on 421 consecutive patients who had undergone lobectomy for NSCLC. Classification of COPD severity was based on guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Characteristics among the three subgroups were compared and recurrence-free survivals were analyzed. RESULTS: A total of 172 patients were diagnosed with COPD, 124 as mild (GOLD-1), 46 as moderate(GOLD-2), and 2 as severe (GOLD-3). The frequencies of recurrence were significantly higher in higher COPD grades group (P<0.001). Recurrence-free survival at five years were 78.1%, 70.4%, and 46.4% in Non-COPD, GOLD-1 COPD, and GOLD-2/3 COPD groups, respectively (P<0.001). In univariate analysis, age, gender, smoking history, COPD severity, tumor size, histology and pathological stage were associated with recurrence-free survival. Multivariate analyses showed that older age, male, GOLD-2/3 COPD, and advanced stage were independent risk factors associated with recurrence-free survival. CONCLUSIONS NSCLC patients with COPD are at higher risk for postoperative recurrence, and moderate/severe COPD is an independent unfavorable prognostic factor. The severity of COPD based on pulmonary function test can be a useful indicator to identify patients at high risk for recurrence. Therefore, it can contribute to adequate selection of the appropriate individualized treatment.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; complications ; mortality ; physiopathology ; surgery ; Female ; Humans ; Lung Neoplasms ; complications ; mortality ; physiopathology ; surgery ; Male ; Middle Aged ; Multivariate Analysis ; Pulmonary Disease, Chronic Obstructive ; complications ; mortality ; physiopathology ; Respiratory Function Tests ; Retrospective Studies

BACKGROUND: Non-small cell lung cancer (NSCLC) is a kind of lung cancer, because its high incidence has been concerned. Therefore, it has great significance to reveal the pathogenesis of NSCLC. As a transcriptional regulatory factor, MATF-A plays an important role in the development of multiple tumors, can regulate the migration process of a variety of tumor cells. HOTAIR is a long non-coding RNA (LncRNA) found in recent years, which expresses abnormally in multiple tumors and is involved in the proliferation and migration of multiple tumors. The aim of this study is to explore the role of MRTF-A through HOTAIR to regulate the proliferation and migration of NSCLC cell A549 cell. METHODS: We constructed the overexpression plasmid and interfering plasmid of MRTF-A, and detected the effect of MRTF-A on the proliferation and migration of A549 cells by CCK8 and wound healing methods respectively. Then, we designed the siRNA of HOTAIR to detect its effect on the proliferation and migration of A549 cells. Through qRT-PCR, we detected the effect of MRTF-A on HOTAIR expression. Finally, we constructed HOTAIR's promoter, and detect the effect of MRTF-A on HOTAIR promoter activity by luciferase reporter gene test. RESULTS: Overexpression of MRTF-A promotes the proliferation and migration of A549 cells, while silent MRTF-A inhibits its proliferation and migration. Next, we found that interfered HOTAIR expression inhibited the proliferation of A549 cells. We found that MRTF-A could influence the expression of HOTAIR and regulate the activity of HOTAIR promoter. CONCLUSIONS MRTF-A regulates the proliferation and migration of A549 cell through HOTAIR.
A549 Cells ; Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; physiopathology ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Humans ; Promoter Regions, Genetic ; RNA, Long Noncoding ; genetics ; metabolism ; Trans-Activators ; genetics ; metabolism

PURPOSE: Patients with non-small cell lung cancer (NSCLC) and simultaneously having brain metastases at the initial diagnosis, presenting symptoms related brain metastasis, survived shorter duration and showed poor quality of life. We analyzed our experiences on surgical treatment of brain metastasis in patients with NSCLC. MATERIALS AND METHODS: We performed a single-center, retrospective review of 36 patients with NSCLC and synchronous brain metastases between April 2006 and December 2011. Patients were categorized according to the presence of neurological symptoms and having a brain surgery. As a result, 14 patients did not show neurological symptoms and 22 patients presented neurological symptoms. Symptomatic 22 patients were divided into two groups according to undergoing brain surgery (neurosurgery group; n=11, non-neurosurgery group; n=11). We analyzed overall surgery (OS), intracranial progression-free survival (PFS), and quality of life. RESULTS: Survival analysis showed there was no difference between patients with neurosurgery (OS, 12.1 months) and non-neurosurgery (OS, 10.2 months; p=0.550). Likewise for intracranial PFS, there was no significant difference between patients with neurosurgery (PFS, 6.3 months) and non-neurosurgery (PFS, 5.3 months; p=0.666). Reliable neurological one month follow up by the Medical Research Council neurological function evaluation scale were performed in symptomatic 22 patients. The scale improved in eight (73%) patients in the neurosurgery group, but only in three (27%) patients in the non-neurosurgery group (p=0.0495). CONCLUSION: Patients with NSCLC and synchronous brain metastases, presenting neurological symptoms showed no survival benefit from neurosurgical resection, although quality of life was improved due to early control of neurological symptoms.
Adult ; Aged ; Aged, 80 and over ; Brain Neoplasms/physiopathology/*secondary/*surgery ; Carcinoma, Non-Small-Cell Lung/mortality/*pathology ; Demography ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/*pathology ; Male ; Middle Aged ; Treatment Outcome

OBJECTIVETo fabricate an innovative scaffold for lung cancer cell culture and establish a three-dimensional lung cancer model in vitro, and to reveal the differences in biological functions of lung cancer cells under the two-dimensional and three-dimensional culture conditions.

METHODSWe chose agarose and alginate as the scaffold materials, and 3D printing technique was applied to construct cell culture scaffold. 95D cells were co-cultured with this scaffold. The differences of cell morphology, proliferation ability, protein expression, etc. in the cells cultured under 2D and 3D cultural conditions were evaluated by light microscopy using HE staining, MTT assay, scanning electron microscopy, and Western blot analysis.

RESULTSCells cultured in 2D wells displayed a spindle and polygonal morphology, whereas those grown in the 3D culture aggregated into spheroids, which invaded, migrated and disseminated into the surrounding scaffold. MTT assay showed that the proliferation rates of the 3D-cultured cells for 2-6 days were significantly lower than, but those cultured for 8-9 days were significantly higher than that of the 2D-cultured cells, indicating that proliferative activity of the cells grown in 2D cultures for 8-9 days was inhibited. In contrast, cells grown on 3D scaffolds still maintained a higher proliferation. The Western blot assay showed that the expression of Cdc42, p53, mTOR were significantly down-regulated in 3D scaffold-cultured group (0.529±0.103, 0.820±0.038 vs. 1.967±0.066), compared with that of the 2D-cultured group (3.063±0.139, 1.738±0.122 vs. 2.472±0.151) (P<0.05 for all), while the expression of MMP-2 was up-regulated in the 3D-cultured cells (1.110±0.029), significantly higher than that of the 2D-cultured cells (0.017±0.001) (P<0.05).

CONCLUSIONSThe cell morphology, proliferation and associated protein expression of lung cancer cells in 3D-culture systems are distinctively different as compared to those of the 2D-cultural cells. 3D-bioprinted agarose-alginate scaffold can better mimic the growth microenvironment of lung cancer in vivo and may provide a promising model for lung cancer research in vitro.

Alginates ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; physiopathology ; Cell Culture Techniques ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Coculture Techniques ; Glucuronic Acid ; Hexuronic Acids ; Humans ; Lung Neoplasms ; metabolism ; pathology ; physiopathology ; Neoplasm Invasiveness ; Neoplasm Proteins ; metabolism ; Printing, Three-Dimensional ; Sepharose ; Spheroids, Cellular ; pathology ; Time Factors ; Tissue Scaffolds ; Tumor Microenvironment

OBJECTIVETo investigate the effect of Shenqi-fuzheng injection combined with chemotherapy on the quality of life in lung cancer patient.

METHODS232 pathologically confirmed nonsmall cell lung cancer patients were enrolled into this multi-center randomized trial. Of these 232 patients, 116 cases were treated with chemotherapy alone (chemotherapy group), another 116 with chemotherapy combined with Shenqi-fuzheng injection produced by Lizhu Company (Shenqi-fuzheng group). Life quality of these patients were evaluated using the QOL scale of European Organization for Research on Treatment of Cancer (QLQ-C30) and the functional living index-cancer.

RESULTSCompared with chemotherapy group, Life quality and symptoms were improved in the Shenqi-fuzheng group, which including lassitude, deficient in breath, pain, fullness in chest and hypochondrium, excessive phlegm, cough, complexion whiteness. Response rate to chemotherapy was also improved. No AE and SAE were observed in the Shenqi-fuzheng group.

CONCLUSIONShenqi-fuzheng injection combined with chemotherapy is safe and effective in the treatment for non-small cell lung cancer.

Adolescent ; Adult ; Aged ; Antineoplastic Agents, Phytogenic ; administration & dosage ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; physiopathology ; Cisplatin ; therapeutic use ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Female ; Humans ; Infusions, Intravenous ; Lung Neoplasms ; drug therapy ; physiopathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Paclitaxel ; Phytotherapy ; Quality of Life ; Taxoids ; therapeutic use ; Young Adult

OBJECTIVETo investigate the role of the expression of ephrinB2 and EphB4 in non-small cell lung cancer (NSCLC), and their relationship with multi-slice spiral CT pulmonary perfusion imaging.

METHODSThirty-one nodules with pathologically proven NSCLC underwent CT perfusion scan. The perfusion parameters including blood flow (BF), blood volume (BV), peak enhancement image (PEI) were collected. The expression of ephrinB2 and EphB4 in tumor cells and interstitial vasculature were detected by immunohistochemistry. Correlation analysis and trend test were used to assess the relationship between ephrinB2/EphB4 expression and clinicopathological features, and between ephrinB2/EphB4 expression and perfusion parameters.

RESULTSPositive expression of ephrinB2 and EphB4 in the NSCLC group was 83.9% and 71.0%, respectively, significantly higher than that in the internal control group (P < 0.01). The expression of ephrinB2 and EphB4 was consistently in tumor parenchyma but differently in tumor vessels. The expressions of ephrinB2 and EphB4 were positively correlated with lymphatic metastasis (P < 0.05). The expression of EphB4 was negatively correlated with blood flow (BF) and blood volume (BV), respectively (P < 0.05). There was a significant positive correlation between ephrinB2 expression and BF (r = 0.516, P = 0.003), and a positive correlation between ephrinB2 expression and BV (r = 0.448, P = 0.013). The expressions of ephrinB2 and EphB4 were not correlated with PEI (P > 0.05). The values of BF and BV in the high and moderate EphB4 expression groups were significantly decreased compared with that in the negative group (P < 0.01). The value of BF in the high ephrinB2 expression group was significantly increased compared with that in the moderately positive group and negative group (P < 0.01). The value of BV in the high ephrinB2 expression group was significantly increased compared with that in the negative group (P < 0.01).

CONCLUSIONThe CT pulmonary perfusion imaging reflects the density difference of blood vessels with functional lumen, and such difference also depends on the quantity and quality of vasculature with functional lumen.

Adult ; Aged ; Blood Volume ; Carcinoma, Non-Small-Cell Lung ; blood supply ; diagnostic imaging ; metabolism ; pathology ; physiopathology ; Ephrin-B2 ; metabolism ; Female ; Humans ; Lung Neoplasms ; blood supply ; diagnostic imaging ; metabolism ; pathology ; physiopathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Perfusion Imaging ; Pulmonary Circulation ; Receptor, EphB4 ; metabolism ; Tomography, Spiral Computed ; methods