Distant Metastasis Of Lung Cancer Research Articles

Negative regulation of SH2B3 by SMYD5 controls epithelial-mesenchymal transition in lung cancer

The main cause of death in lung cancer patients is metastasis. Thus, efforts to suppress micrometastasis or distant metastasis in lung cancer, identify therapeutic targets and develop related drugs are ongoing. In this study, we identified SMYD5 as a novel metastasis regulator in lung cancer and found that SMYD5 was overexpressed in lung cancer based on both RNA-sequencing (RNA-seq) analysis results derived from the TCGA portal and immunohistochemical analysis results; knockdown of SMYD5 inhibited cell migration and invasion by changing EMT (epithelial-mesenchymal transition) markers and MMP9 expression in NCI-H1299 and H1703 cell lines. Additionally, SMYD5 knockdown increased SH2B3 expression by decreasing the level of H4K20 trimethylation. Furthermore, in an in vitro EMT system using TGF-β treatment, SMYD5 knockdown resulted in reduced cell migration and invasion in the highly invasive NCI-H1299 and H1703 cell lines. Based on these findings, we propose that SMYD5 could serve as a potential therapeutic target for lung cancer treatment and that cotreatment with an SMYD5 inhibitor and chemotherapy may enhance the therapeutic effect of lung cancer treatment.

Inaugural Scalp Metastasis of Pulmonary Squamous Cell Carcinoma: A Rare Case Report and Literature Review

Distant cutaneous metastasis of primary lung squamous cell carcinoma is an exceedingly rare event, with scalp metastasis as the initial clinical presentation even rarer. Scalp skin metastases are prone to be misdiagnosed as other scalp disorders, yet their appearance signifies the deterioration and poor prognosis of lung cancer. This case report documents a female patient presenting initially with scalp folliculitis in dermatology, who was subsequently diagnosed with malignant lung tumor through radiological imaging and referred to Department of Thoracic Surgery. Pathological examination of the excised lesion from the scalp revealed distant metastasis of lung cancer. A review of similar cases reported in literature was conducted. This article aims to enhance understanding and awareness of skin metastasis in lung cancer, to emphasize the importance of this condition, and to improve early recognition and precise diagnosis. It is crucial to prevent clinical misdiagnosis and ensure appropriate treatment, finally leading to improve the prognosis of the patients. .

Prognosis value of IL-6, IL-8, and IL-1β in serum of patients with lung cancer: A fresh look at interleukins as a biomarker

Interleukins are assumed to be closely related to the occurrence and development of human malignant tumors, while a few of them were commonly used as diagnostic markers in clinical cancer, including lung cancer. This study aimed to explore the value of serum interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) combined with carcinoembryonic antigen (CEA) as biomarker panel for the diagnosis and metastasis prediction of lung cancer. IL-1β, IL-6, IL-8, and CEA in serum were determined using electrochemiluminescence immunoassay (ECLIA) and flow cytometry, and the diagnostic value of each marker was analyzed using receiver operating characteristic (ROC) curves and logistic fitting regression. We found that the levels of serum IL-1β, IL-6, and IL-8 showed no significant difference among squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, while they were significantly higher in the lung cancer group or benign group than those in the healthy group. The levels of IL-8 and CEA were positively correlated with clinical stages respectively. Importantly, the panel of CEA + IL-6 + IL-8 has the highest efficacy for the diagnosis of lung cancer (AUC = 0.883) among all the detected panels, while the panel of IL-8 + CEA showed the most promising predictive value for the lymph node metastasis (AUC = 0.686) and distant metastasis of lung cancer (AUC = 0.793). In conclusion, IL-6 and IL-8 could be used as promising molecular biomarkers to diagnose and predict the metastasis of lung cancer independent of pathological types, improving the specificity and sensitivity of diagnosis for lung cancer when they were combined with CEA.

Distant Metastasis Patterns of Lung Cancer on Positron Emission Tomography/Computed Tomography Association with Age and Histological Subtype

To investigate whether age or other factors are determinants of distant metastasis in patients with lung cancer.Observational study.Department of Nuclear Medicine, Recep Tayyip Erdogan University, Rize, Turkey between December, 2018 and February, 2019.A total of 152 patients with lung cancer, who underwent positron emission tomography/computed tomography (PET/CT) for staging, were included in this study. Patients were grouped according to age (>65 and <65 years) and distant metastasis status. Metastasis localisation of patients was evaluated by PET/CT. Univariate/multivariate regression analyses were performed to determine risk factors for distant metastasis.No significant difference was found when the relation of distant metastasis with stage distribution was examined in both age groups. Distant metastasis rates were significantly higher in female patients than in male patients (p = 0.019) and in patients with small-cell lung carcinoma (SCLC)-adenocarcinoma than in those with other histopathological subtypes (p <0.001). Most of the patients in both groups had a stage 4 disease, and bone distant metastasis was the most common in both age groups. Univariate/multivariate analyses identified that female gender (p = 0.017/p = 0.003), SCLC subtype (p = 0.013/p = 0.008), T3/T4 tumour (p <0.001/p <0.001), and smoking history of >66 pack-years (p = 0.047/p = 0.047) were independent factors for the presence of distant metastasis.Although age is not a risk factor for distant metastasis in lung cancer, female gender, T3/4 tumour, SCLC subtype, and smoking history of >66 pack-years are high-risk factors. PET/CT is recommended as the first-choice imaging technique in patients with lung cancer indicated for distant metastasis scanning. Key Word: Lung cancer, PET/CT, Metastases, Histological subtype, T-stage.

LC3A-mediated autophagy regulates lung cancer cell plasticity

ABSTRACT Cancer cell plasticity generates heterogeneous oncogenic subpopulations in tumors. How macroautophagy/autophagy, a catabolic system required for sustaining cell homeostasis, affects cancer cell plasticity, remains elusive. In this study, we report that MAP1LC3A/LC3A (microtubule associated protein 1 light chain 3 alpha), a key molecule in autophagy, is negatively associated with histological grade and distant metastasis of lung cancer. This is achieved in part, if not all, by maintaining the mitochondria and energy homeostasis to meet the proliferation demand of lung cancer cells driven by SOX2 (SRY-box transcription factor 2) signaling. Basal autophagy is preferentially active in SOX2-positive lung cancer cells with high-proliferative and low-invasive properties. The high-proliferative cancer cells exhibit higher oxygen consumption rate (OCR), elevated reactive oxygen species (ROS), and profound fragmented mitochondrial patterns compared to their high-invasive counterparts. SOX2 expression promotes LC3A expression and enhances proliferation but attenuates invasion in lung cancer cells. LC3A silencing enriches cells harboring low-proliferative and high-invasive features, concomitant with decreased OCR and ROS levels and reduced expression of SOX2. Our findings provide novel insights into how basal autophagy cross talks with SOX2 proliferation signaling to regulate mitochondrial metabolism and determines cancer cell plasticity with an impact on lung tumor progression. Abbreviations ATG14: autophagy related 14; CDH2: cadherin 2; ChIP-qPCR: chromatin immunoprecipitation quantitative polymerase chain reaction; CQ: chloroquine; ECAR: extracellular acidification rate; EMT: epithelial-mesenchymal transition; EPCAM: epithelial cell adhesion molecule; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAP1LC3C/LC3C: microtubule associated protein 1 light chain 3 gamma; NDUFV2: NADH:ubiquinone oxidoreductase core subunit V2; OCR: oxygen consumption rate; ROS: reactive oxygen species; RT-qPCR: reverse-transcriptase quantitative polymerase chain reaction; SC: scrambled control; shRNA: short hairpin RNA; SNAI2: snail family transcriptional repressor 2; SOX2: SRY-box transcription factor 2; SQSTM1/p62: sequestosome 1; TGFB/TGF-β: transforming growth factor beta; TOMM20: translocase of outer mitochondrial membrane 20; ZEB1: zinc finger E-box binding homeobox 1

BSCI-09. Multiomic single cell analysis reveals emerging principles of tumor immune microenvironment inherent to NSCLC brain metastases

Brain is one of the most common sites for distant metastasis of lung cancer. Treatment naïve lung cancer patients diagnosed with brain metastasis are left with very limited options. Checkpoint inhibition is a powerful immunotherapy strategy but delivers benefit only to a small population of patients. Here we harnessed the power and resolution of single cell RNA sequencing and single cell TCR/BCR sequencing to investigate the tumor immune microenvironment (TIME) of NSCLC brain metastases. We enrolled treatment naïve lung cancer patients with brain metastasis. The enrolled subjects covered different histology types and driver gene mutation status. We revealed the emerging principles of innate and adaptive immune components inherent to NSCLC brain metastases. We also uncovered several significant intercellular communication patterns that potentiates cancer cell seeding and fosters cancer cell proliferation. Those results served as a starting point to design optimal immunotherapy strategies for advanced lung cancer patients with limited options.

Diagnosis of Distant Metastasis of Lung Cancer Using Anarchic Society Optimization with Support Vector Machine

The most widely recognized threatening tumours is the lung cancer one amongst the most preeminent disease and mortality which prompts significant risk to individuals’ wellbeing and life. Propelled lung malignant growth is probably prompt to produce comparing side effects in patients with extraordinary torment and life-threatening. Computed Tomography (CT) is one of the efficient solutions to investigate the distant metastasis plausibility for which system with computer aided diagnosis is desirable. So to diagnose distant metastasis of cancer in lung, the past framework is accomplished by Support Vector Machine (SVM) based classification for manual segmentation and the precision achieved is 89.09% for the classification. To enumerate large data sets, manual segmentation is time consuming, tedious and labour-intensive and hence achieving feasibility is not that easy. The desired prediction accuracy is attained by the techniques namely efficient segmentation method and feature selection methods. The proposed system utilizes Improved Markov Random Field (MRF) with SVM based classification, thereby improving the system performance. In this research work, the input is nothing but the CT lung images and adaptive median filtering is utilized for preprocessing technique. Improved MRF approach is one of the solutions to segment the pre-processed image after which CT images are used to extricate the clinical features and radiomic features. Anarchic Society Optimization (ASO) algorithm provides assistance for choosing the optimal features which in turn progresses the classification accuracy. In view of the selected feature, SVM classifier is utilized for cancer classification. The test outcome proves that the projected framework achieves improved performance compared to the existing frameworks parameters like correctness, accuracy and review.

Detection of Distant Lung Cancer using Enhanced Transductive Support Vector Machines

Background: Cancer disease is the second largest disease after heart-attack in the world. Cancer is an abnormal growth of normal cell. Cancer is classified based on the cell type where it is mainly affected .There are different types of cancer like blood cancer, brain cancer, small intestine cancer, lung cancer, liver cancer etc. According to ICMR, among 1.27 billion Indian populations, the incidence of cancer is 70 – 90% per 100,000 populations and 70% of cancer is identified in the last stage accounting for high mortality. Though there are hundred form of cancer, the prognosis of bronchogenic carcinoma (lung cancer) is very poor because it can be identified only at a final stage. The beginning tumors are not more dangerous but the malignant tumors are more risky which spread to further portions of the body over blood stream or the lymph vessels. Prognosis and remedy is the biggest provocations in cancer for the medical field and physicians in the past few years. The CT scans support the doctors to detect cancer at early stage. When cancer is prognoses at benign stage, millions of human life across the world gets saved every year. Method: Noise in the CT scan input image is reduced by traditional adaptive median filtering and segmented by Region Based Neural Networks to extract a region of interest. To reduce the unwanted texture and noises and to detect wide-ranged images, Improved Canny Edge detector is implemented. The clinical characteristics of the patient were included as a feature reference. The considered features in clinical characteristics are status of patient smoking ,age of the patient, classification of tumor and T, N staging. Feature selection using Improved Glowworm Swarm Optimization and Classification Enhanced Transductive Support Vector Machines (ETSVM) is utilized to diagnose the distant metastasis of lung cancer. Result: Experimental results shows that ETSVM and Improved Glowworm Swarm Optimization achieved the best performance with an accuracy 90.7% and sensitivity 94.7%.

Cyclin K interacts with β-catenin to induce Cyclin D1 expression and facilitates tumorigenesis and radioresistance in lung cancer.

Rationale: Radioresistance remains the major cause of local relapse and distant metastasis in lung cancer. However, the underlying molecular mechanisms remain poorly defined. This study aimed to investigate the role and regulatory mechanism of Cyclin K in lung cancer radioresistance.Methods: Expression levels of Cyclin K were measured by immunohistochemistry in human lung cancer tissues and adjacent normal lung tissues. Cell growth and proliferation, neutral comet and foci formation assays, G2/M checkpoint and a xenograft mouse model were used for functional analyses. Gene expression was examined by RNA sequencing and quantitative real-time PCR. Protein-protein interaction was assessed by immunoprecipitation and GST pull-down assays.Results: We report that Cyclin K is frequently overexpressed and correlates with poor prognosis in lung cancer patients. Functionally, we demonstrate that Cyclin K depletion results in reduced proliferation, defective G2/M checkpoint and enhanced radiosensitivity in lung cancer. Mechanistically, we reveal that Cyclin K interacts with and promotes the stabilization of β-catenin protein, thereby upregulating the expression of Cyclin D1. More importantly, we show that Cyclin D1 is the major effector that mediates the biological functions of Cyclin K in lung cancer.Conclusions: These findings suggest that Cyclin K positively modulates the β-catenin/Cyclin D1 axis to promote tumorigenesis and radioresistance in lung cancer, indicating that Cyclin K may represent a novel attractive biomarker for lung cancer radiotherapy.

The clinical significance of serum adipocytokines level in patients with lung cancer.

Adipocytokines were known to play a relevant role in metabolism, inflammation responses and carcinogenesis of several malignancies. Our aims were to detect the expression of serum adipocytokines, explore their potential diagnostic ability and relationship with clinicopathological characteristics of lung cancer. Adipocytokines, insulin-like growth factor binding protein 1 (IGFBP-1), resistin, tumor necrosis factors (TNFα), TNF RI and TNF RII, vascular endothelial growth factor (VEGF), leptin, interleukin (IL)-6 and IL-10, chemerin, brain-derived neurotrophic factor (BDNF), plasminogen activator inhibitor-1 (PAI-1) were assessed in 49 untreated lung cancer patients and 20 healthy controls. The protein chip was used to detect the serum levels of adipocytokines. Lung cancer patients exhibited significantly elevated serum IGFBP-1, TNF RI, VEGF, TNF RII, PAI-1 and IL-6 levels compared to controls (P<0.05) and most of these adipocytokines revealed a modest discriminative ability for the diagnosis of lung cancer, while BDNF were lower in patients (P<0.05). TNF RI was associated with distant metastasis of lung cancer, while there was no relation between other adipocytokines and the patient clinicopathological features. These results suggest that cytokines IGFBP-1, TNF RI, VEGF, TNF RII, PAI-1 and IL-6 may be involved in the development and progression of lung cancer, and TNF RI may be involved in distant metastasis of lung cancer. Additionally, IGFBP-1, TNF RI, VEGF and TNF RII probably represent potentially useful biomarkers for the diagnosis of lung cancer.

Cisplatin resistant lung cancer cells promoted M2 polarization of tumor-associated macrophages via the Src/CD155/MIF functional pathway

BackgroundLung cancer often ranks one of the most prevalent malignancies in the world. One of the most challenging aspects of treating late-stage lung cancer patients is the development of drug resistance, from both conventional chemo- and targeted therapeutic agents. Tumor-associated microphages (TAMs) have been shown to promote the survival and distant metastasis of lung cancer cells.MethodsThis study investigated the TAMs - modulating potential of cisplatin-resistant non-small cell lung cancer (NSCLC) cell lines, A549R and H460R by using bioinformatics approach, immunoblotting, immunofluorescence staining, migration, invasion, colony, lung sphere formation and xenograft tumorigenecity assays.ResultsIn this study, we first demonstrated the elevated expression of oncogenic and stemenss markers such as Src, Notch1, macrophage inhibitory factor (MIF) and CD155 in trained cisplatin (CDDP)-resistant A549 and H460 cells (A549R and H460R cells). When co-cultured with TAMs, A549R and H460R cells promoted the M2-polarization in TAMs. In addition, A549R and H460R cells showed an increased self-renewal ability as they formed tumor spheres at higher frequency comparing to their parental counterparts. The increased MIF secretion by the A549R and H460R cells could be suppressed by a multiple kinase inhibitor, dasatinib, which resulted in the decreased of oncogenic network of Src, CD155 and MIF expression. Similarly, dasatinib treatment reduced the M2 polarization in TAMs and suppressed self-renewal ability of the A549R and H460R cells.ConclusionIn summary, cisplatin resistant lung cancer cells not only showed an increased self-renewal ability but also promoted M2 polarization of TAMs via the secretion of MIF. These findings were linked to the increased Src-associated signaling as dasatinib treatment significantly reversed these phenomena. Thus, kinase inhibitors such as dasatinib may be of potential for treating cisplatin-resistant lung cancer by targeting both tumor and the tumor microenvironment.Graphical abstract

Analysis of platelet parameters and activation markers in hematologic metastases of lung cancer.

Analysis of platelet parameters and activation markers in hematologic metastases of lung cancer.

An 8-Mm Polyp Is Worth a 1,000 Words: Metastatic Lung Cancer Within a Tubular Adenoma

Introduction: Lung cancer is the leading cause of cancer deaths in the United States, and cases are often metastatic at the time of diagnosis. We report a case of metastatic lung cancer initially diagnosed incidentally when a metastatic lesion was found within a tubular adenoma. Case Description: A 64-year-old male with thirty pack-year smoking history presented to the hospital with left lower extremity swelling and found to have an extensive unprovoked deep vein thrombosis. He was placed on rivaroxaban. The patient returned to hospital two weeks later with painless hematochezia. Colonoscopy was performed but did not identify a source of bleeding. However, an 8 mm polyp in the sigmoid colon were resected. Pathology results revealed a tubular adenoma containing poorly differentiated adenocarcinoma invading the lamina propria, consistent with pulmonary origin (TTF1 and CK7 positive; CK20, CDX2, GATA3 and S100 negative). Subsequent CT chest/abdomen/pelvis demonstrated multiple spiculated pulmonary nodules and enlarged supraclavicular, cervical, mediastinal and hilar nodes consistent with metastatic lung cancer. Based on the mutation pattern (PD-L1 positive; EGFR/Alk/Ros unmutated), the patient received pembrolizumab as palliative treatment.1538_A Figure 1. Chromogenic photomicrograph of colonic tubular adenoma showing metastatic poorly differentiated adenocarcinoma with negative CDX2 (specific for intestinal epithelium) staining. (x10 magnification)Discussion: Lung cancer is one of the most common primary malignancies with nearly 50% distal metastasis at the time of diagnosis. However, intestinal metastases are considered quite rare. The prevalence of metastasis to GI tract varies by report from 0.5-14%. The most common histologic types are SCC and large cell. Of the potential GI tract metastasis, the most sites are the esophagus, small intestine, and stomach. When colonic metastasis are present, two-thirds of patients are symptomatic at the time of the diagnosis and most commonly describe symptoms of abdominal pain, nausea, vomiting, and weight loss. Metastases to the GI tract are most often encountered during evaluation of symptomatic cases. In the asymptomatic patient they are often found incidentally on imaging or autopsy. Distant metastasis in lung cancer confers poor prognosis. Diagnostic modalities such as colonoscopy likely do not provide mortality benefit but less is known regarding morbidity and prevention of GI complications. In conclusion, lung cancer metastasis to the colon is exceedingly rare, and this is the first reported case of a metastatic lung cancer within a colon polyp.1538_B Figure 2. Chromogenic photomicrograph of poorly differentiated carcinoma showing positive staining for TTF1 (specific for primary lung adenocarcinomas). (x20 magnification)1538_C Figure 3. Spiculated nodular opacity in the left upper lobe anteriorly in an area of focal emphysema measuring 1 cm.

Correlation between circulating tumor cells and D-D and platelet in patients with pulmonary malignancies.

The aim of the present study was to investigate the correlation between circulating tumor cells (CTC) and D-dimer (D-D) and platelet (PLT) in patients with pulmonary malignancies. A total of 98 patients with lung cancer admitted to West China Hospital, Sichuan University, from June 2016 to February 2017 were enrolled in the present study. D-D and PLT levels were measured in the fasting elbow vein of the patients. The expression of CTC in peripheral blood was detected by negative separation using immunomagnetic beads and immunocytochemical staining. The correlation between CTC and D-D and PLT in patients with lung cancer was analyzed. The mean level of D-D in the peripheral blood of 98 patients was 1.80±1.63 µg/l, and the level of D-D was correlated with distant metastasis (P<0.05). The mean level of PLT in peripheral blood was 305.53±141.22×109/l in 98 patients, and the level of PLT was correlated with patient age, clinical stage and distant metastasis (P<0.05). The levels of D-D, PLT and distant metastasis were significantly higher in CTC-positive than in CTC-negative patients (P<0.05). Therefore, CTC can predict the distant metastasis of lung cancer, and the incidence of distant metastasis is high in patients with hypercoagulable state.

Diagnosis of Distant Metastasis of Lung Cancer: Based on Clinical and Radiomic Features

OBJECTIVES: To analyze the distant metastasis possibility based on computed tomography (CT) radiomic features in patients with lung cancer. METHODS: This was a retrospective analysis of 348 patients with lung cancer enrolled between 2014 and February 2015. A feature set containing clinical features and 485 radiomic features was extracted from the pretherapy CT images. Feature selection via concave minimization (FSV) was used to select effective features. A support vector machine (SVM) was used to evaluate the predictive ability of each feature. RESULTS: Four radiomic features and three clinical features were obtained by FSV feature selection. Classification accuracy by the proposed SVM with SGD method was 71.02%, and the area under the curve was 72.84% with only the radiomic features extracted from CT. After the addition of clinical features, 89.09% can be achieved. CONCLUSION: The radiomic features of the pretherapy CT images may be used as predictors of distant metastasis. And it also can be used in combination with the patient's gender and tumor T and N phase information to diagnose the possibility of distant metastasis in lung cancer.

High FDG uptake on PET is associated with negative cell-to-cell adhesion molecule E-cadherin expression in lung adenocarcinoma.

E-cadherin is a main cell-to-cell adhesion molecule. A negative expression of E-cadherin correlates with distant metastasis in lung cancer. Recently, it was reported that there is an association between FDG uptake on PET and epithelial-mesenchymal transition (EMT) in non-small cell lung cancer. Downregulation of E-cadherin is one of the best markers of EMT. The purpose of this study was to compare E-cadherin expression with FDG uptake on PET, cell differentiation, aggressiveness and post-operative recurrence in patients with lung adenocarcinoma, and to investigate whether FDG uptake on PET is associated with E-cadherin expression. We retrospectively reviewed 40 lung adenocarcinoma patients who underwent thoracotomy and FDG PET before thoracotomy. These patients were evaluated FDG PET metrics such as standardized uptake value (SUV), the immunohistochemical expression of E-cadherin in surgical specimens, clinicopathological features, including tumor size, pathologic stage, cell differentiation, aggressiveness and post-operative recurrence. High FDG uptake correlated with negative E-cadherin expression (P=0.043). SUVmax was higher in a negative E-cadherin expression lung adenocarcinoma than in a positive E-cadherin expression lung adenocarcinoma (P=0.033). Patients with moderately poorly differentiated adenocarcinoma had frequent negative E-cadherin expression or high FDG uptake (P=0.004, P=0.0001, respectively). Patients with aggressive adenocarcinoma had frequent negative E-cadherin expression or high FDG uptake (P=0.004, P=0.001, respectively). Kaplan-Meier analysis revealed that negative E-cadherin expression or high FDG uptake were strongly correlated with shortened disease-free survival (P=0.0153, P=0.0001, respectively). High FDG uptake on PET was associated with negative E-cadherin expression in patients with lung adenocarcinoma. Both high FDG uptake and negative E-cadherin expression were strongly correlated with poor differentiation, aggressiveness, and post-operative recurrence. These findings may cause the association between high FDG uptake and negative E-cadherin expression.

CDK20 interacts with KEAP1 to activate NRF2 and promotes radiochemoresistance in lung cancer cells.

Radiochemoresistance is considered the main cause of local recurrence and distant metastasis in lung cancer. However, the underlying mechanisms of radiochemoresistance remain to be uncovered. In this study, we determine the functions of cell cycle-related kinase (CDK20) in radiochemoresistance. CDK20 is a newly identified protein kinase, which plays critical roles in cell growth and proliferation in several types of cancer. Using tandem affinity purification technology, we provide evidences that CDK20 binds to the ubiquitin ligase Kelch-like ECH-associated protein 1 (KEAP1), which targets transcriptional factor nuclear factor erythroid-2-related factor 2 (NRF2) for degradation. We show that this interaction is mediated by an evolutionarily conserved ETGE motif on CDK20. Furthermore, we demonstrate that CDK20 competes with NRF2 for KEAP1 binding, enhances the transcriptional activity of NRF2 and lowers the cellular reactive oxygen species level. Moreover, CDK20-depleted cells display impaired cell proliferation, defective G2/M arrest and increased radiochemosensitivity in lung cancer. These phenotypes induced by CDK20 knockdown are partially dependent on NRF2 inactivation. More importantly, CDK20 is overexpressed in human lung cancer tissues, as determined by immunostaining. Collectively, our results suggest that CDK20 positively modulate the KEAP1-NRF2 cytoprotective pathway to regulate tumor progression and radiochemoresistance, implying that CDK20 is a novel, promising therapeutic target for lung cancer.

Relationship between circulating tumor cells and coagulation factors in primary lung cancer patients

To investigate the relationship between the presence of circulating tumor cells (CTC) and the values of coagulation factors including D-dimer (D-D), fibrinogen (FIB) and platelet (PLT) in primary lung cancer patients. Peripheral venous blood samples were collected from 79 patients with previously untreated primary lung cancer. The levels of D-D, FIB and PLT were detected. The CTCs were enriched by negative immunomagnetic separation with anti-CD45 antibody and then detected by immunocytochemistry with Anti-pan Cytokeratin antibody. The relationship between these parameters and clinicopathologic characteristics of the patients was analyzed. The levels of D-D, FIB and PLT were( 1.74±2.04) mg/L, (3.51±1.46 )g/L, (311±139)×10(9)/L, respectively. The level of D-D was associated with distant metastasis of lung cancer (P=0.046). The level of FIB was associated with clinical stage and distant metastasis (P<0.05). The level of PLT was associated with age, clinical stage and distant metastasis (all P<0.05). Among the 79 patients, there were 45 CTC-positive and 34 CTC-negative cases. The levels of D-D in the CTC-positive and CTC-negative groups were (2.31±2.41)mg/L and (0.99±1.02)mg/L, those of FIB were (3.79±1.56)g/L and (3.14±1.25)g/L, and those of PLT were (338±130)×10(9)/L and (229±129)×10(9)/L, respectively(P<0.05 for all). The positive rate of CTC was significantly higher in the metastasis group (82.8%), significantly higher than that in the non-metastatic group (42.0%, P<0.001). The levels of D-D, FIB and PLT in the metastasis group were (2.33±1.95)mg/L, (4.13±1.43)g/L and (433±74)×10(9)/L, but were (1.40±2.03) mg/L, (3.15±1.37)g/L and (206±88)×10(9)/L in the non-metastatic group (P<0.05 for all). The detection of circulating tumor cells may facilitate early prediction of distant metastasis of lung cancer. The hypercoagulation state is more-likely correlated with the distant metastasis of lung cancer.

Discovery of prognostic biomarkers for predicting lung cancer metastasis using microarray and survival data.

BackgroundFew studies have investigated prognostic biomarkers of distant metastases of lung cancer. One of the central difficulties in identifying biomarkers from microarray data is the availability of only a small number of samples, which results overtraining. Recently obtained evidence reveals that epithelial–mesenchymal transition (EMT) of tumor cells causes metastasis, which is detrimental to patients’ survival.ResultsThis work proposes a novel optimization approach to discovering EMT-related prognostic biomarkers to predict the distant metastasis of lung cancer using both microarray and survival data. This weighted objective function maximizes both the accuracy of prediction of distant metastasis and the area between the disease-free survival curves of the non-distant and distant metastases. Seventy-eight patients with lung cancer and a follow-up time of 120 months are used to identify a set of gene markers and an independent cohort of 26 patients is used to evaluate the identified biomarkers. The medical records of the 78 patients show a significant difference between the disease-free survival times of the 37 non-distant- and the 41 distant-metastasis patients. The experimental results thus obtained are as follows. 1) The use of disease-free survival curves can compensate for the shortcoming of insufficient samples and greatly increase the test accuracy by 11.10%; and 2) the support vector machine with a set of 17 transcripts, such as CCL16 and CDKN2AIP, can yield a leave-one-out cross-validation accuracy of 93.59%, a test accuracy of 76.92%, a large disease-free survival area of 74.81%, and a mean survival prediction error of 3.99 months. The identified putative biomarkers are examined using related studies and signaling pathways to reveal the potential effectiveness of the biomarkers in prospective confirmatory studies.ConclusionsThe proposed new optimization approach to identifying prognostic biomarkers by combining multiple sources of data (microarray and survival) can facilitate the accurate selection of biomarkers that are most relevant to the disease while solving the problem of insufficient samples.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0463-x) contains supplementary material, which is available to authorized users.

Surgery for Isolated Metachronous Thyroid Metastasis in a Non-small Cell Lung Carcinoma Patient with Hashimoto?s Thyroiditis: A Case Report

Non-small cell lung cancer (NSCLC) is the one of the leading causes of cancer deaths in Western population. Chemotherapy with platinum-based regimens is the first line management for majority of advanced NSCLC. Distant metastasis in lung cancer commonly involves the adrenal glands, liver, bones and brain. Metastatic involvement of the thyroid gland is infrequent despite its rich vascular supply. Here, we report a case of thyroid metastasis of NSCLC as a primary which was treated by thyroidectomy which is not the conventional approach. A 71 year-old female with a solitary left lower lobe lung mass was diagnosed with invasive poorly-differentiated adenocarcinoma. She was treated with cisplatin and pemetrexed followed by video-assisted thoracoscopic left lower lobectomy. The resected mass showed poorly-differentiated adenocarcinoma and was staged as pT2bN0 (Stage IIA). On a surveillance Computed Tomography (CT) chest, a left thyroid nodule was noted with findings consistent with Hashimoto's thyroiditis in a multinodular goiter. Fine-needle aspiration biopsy was consistent with metastasis from lung primary. This represented a solitary site of metastasis based on positron emission tomography (PET) Scan. Metastatic involvement of thyroid gland is infrequent despite its rich vascular supply. Given the long disease-free interval (DFI) of 1.5 years from initial diagnosis to documentation of isolated thyroid metastasis, she underwent total thyroidectomy followed by platinum-based adjuvant chemotherapy. Patient continues to be disease-free for more than 3 years as of her last follow up. A greater than 3-year disease-free survival to date in this case demonstrates that thyroidectomy can be a successful approach in the management of isolated metachronous thyroid metastasis from NSCLC in the well-selected patient.