Fluoxetine Successfully Treats Intracranial Enterovirus E18 Infection in a Patient with CD79a Deficiency Arising from Segmental Uniparental Disomy of Chromosome 19.

The pre BCR complex plays a crucial role in B cell production, and its successful expression marks the B cell differentiation from the pro-B to pre-B. The CD79a and CD79b mutations, encoding Igα and Igß respectively, have been identified as the cause of autosomal recessive agammaglobulinemia (ARA). Here, we present a case of a patient with a homozygous CD79a mutation, exhibiting recurrent respiratory infections, diarrhea, growth and development delay, unique facial abnormalities and microcephaly, as well as neurological symptoms including tethered spinal cord, sacral canal cyst, and chronic enteroviral E18 meningitis. Complete blockade of the early B cell development in the bone marrow of the patient results in the absence of peripheral circulating mature B cells. Whole exome sequencing revealed a Loss of Heterozygosity (LOH) of approximately 19.20Mb containing CD79a on chromosome 19 in the patient. This is the first case of a homozygous CD79a mutation caused by segmental uniparental diploid (UPD). Another key outcome of this study is the effective management of long-term chronic enteroviral meningitis using a combination of intravenous immunoglobulin (IVIG) and fluoxetine. This approach offers compelling evidence of fluoxetine's utility in treating enteroviral meningitis, particularly in immunocompromised patients.

Traffic Accident Data Generation Based on Improved Generative Adversarial Networks.

For urban traffic, traffic accidents are the most direct and serious risk to people's lives, and rapid recognition and warning of traffic accidents is an important remedy to reduce their harmful effects. However, research scholars are often confronted with the problem of scarce and difficult-to-collect accident data resources for traffic accident scenarios. Therefore, in this paper, a traffic data generation model based on Generative Adversarial Networks (GAN) is developed. To make GAN applicable to non-graphical data, we improve the generator network structure of the model and used the generated model to resample the original data to obtain new traffic accident data. By constructing an adversarial neural network model, we generate a large number of data samples that are similar to the original traffic accident data. Results of the statistical test indicate that the generated samples are not significantly different from the original data. Furthermore, the experiments of traffic accident recognition with several representative classifiers demonstrate that the augmented data can effectively enhance the performance of accident recognition, with a maximum increase in accuracy of 3.05% and a maximum decrease in the false positive rate of 2.95%. Experimental results verify that the proposed method can provide reliable mass data support for the recognition of traffic accidents and road traffic safety.

Hazardous Traffic Event Detection Using Markov Blanket and Sequential Minimal Optimization (MB-SMO).

The ability to identify hazardous traffic events is already considered as one of the most effective solutions for reducing the occurrence of crashes. Only certain particular hazardous traffic events have been studied in previous studies, which were mainly based on dedicated video stream data and GPS data. The objective of this study is twofold: (1) the Markov blanket (MB) algorithm is employed to extract the main factors associated with hazardous traffic events; (2) a model is developed to identify hazardous traffic event using driving characteristics, vehicle trajectory, and vehicle position data. Twenty-two licensed drivers were recruited to carry out a natural driving experiment in Wuhan, China, and multi-sensor information data were collected for different types of traffic events. The results indicated that a vehicle's speed, the standard deviation of speed, the standard deviation of skin conductance, the standard deviation of brake pressure, turn signal, the acceleration of steering, the standard deviation of acceleration, and the acceleration in Z (G) have significant influences on hazardous traffic events. The sequential minimal optimization (SMO) algorithm was adopted to build the identification model, and the accuracy of prediction was higher than 86%. Moreover, compared with other detection algorithms, the MB-SMO algorithm was ranked best in terms of the prediction accuracy. The conclusions can provide reference evidence for the development of dangerous situation warning products and the design of intelligent vehicles.

The Bim deletion polymorphism clinical profile and its relation with tyrosine kinase inhibitor resistance in Chinese patients with non-small cell lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely used for the treatment of patients with advanced non-small cell lung cancer (NSCLC) who have EGFR mutations. Recent studies have indicated that some patients with positive mutations were refractory to EGFR TKIs if they harbored a B-cell chronic lymphocytic leukemia/lymphoma (Bcl-2)-like 11 (Bim) deletion polymorphism. The objective of the current work was to retrospectively study the Bim deletion polymorphism in Chinese patients with NSCLC and its correlation with the efficacy of EGFR TKIs. METHODS: Distribution of the Bim polymorphism was detected using polymerase chain reaction analysis and direct sequencing of DNA from peripheral neutrophils in samples from 352 patients with NSCLC. Of the 352 patients, 166 who received TKI therapy and had an activating mutation identified were involved in further analysis. Progression-free survival (PFS) was the primary endpoint of the subsequent analyses, and the incidence of the Bim polymorphism and its relation to clinical benefit from EGFR TKIs also were investigated. RESULTS: In total, 45 of 352 patient samples (12.8%) had the Bim deletion polymorphism, which was distributed randomly with regard to various clinical characteristics. In patients with EGFR mutations who received treatment with TKIs, the median PFS and the median objective response rate were 4.7 months and 25%, respectively, for those with the Bim deletion polymorphism versus 11 months (P = .003) and 66% (P = .001), respectively, for those with wild-type Bim. Cox regression analysis identified Bim status (P = .016) and sex (P = .002) as independent factors predicting clinical benefit from EGFR TKIs in patients with EGFR-mutated NSCLC. CONCLUSIONS: The incidence of the Bim deletion polymorphism was approximately 13% in this study, and it was associated with a poor clinical response to EGFR TKIs in patients who had NSCLC with EGFR mutations.

Imaging diagnosis and surgical treatment of popliteal artery entrapment syndrome: a single-center experience.

BACKGROUND: In this study we report our experience with the diagnosis and surgical treatment of popliteal entrapment syndrome (PAES) over a 10-year period. METHODS: Between 2002 and 2011, PAES was diagnosed in 27 limbs of 24 patients (19 males and 5 females), based on clinical symptoms and imaging examinations. The mean age of the patients was 30.4 years (range 8-69 years). All patients underwent surgical decompression of the entrapment mechanism and selective vascular reconstruction. Oral aspirin and warfarin therapy was administered after discharge. RESULTS: All patients underwent successful surgical treatment. No perioperative complications occurred. Clinical symptoms either disappeared or exhibited obvious improvement in all patients after surgery. No patient presented with recurrent symptoms after discharge. Doppler ultrasound during follow-up revealed the patency of the popliteal artery and saphenous vein grafts. CONCLUSIONS: PAES is an unusual but major cause of peripheral arterial insufficiency, particularly in patients lacking risk factors for atherosclerosis. A combination of imaging examinations is required for an early and accurate diagnosis. Surgical decompression and selective vascular reconstruction is recommended for both anatomic and symptomatic functional entrapment.

Malignant mediastinal mesothelioma treated with anlotinib: a case report and review of the literature.

Malignant mesothelioma that originates from mediastinal (MMM) is a rare form of malignant pleural mesothelioma (MPM). The prognosis of advanced stage MPM was poor, and the traditional treatment was chemotherapy. Here, we present a patient with MMM that was treated with anlotinib, a multitargeted tyrosine kinase inhibitor (TKI) who had a 24-month progression-free survival (PFS). Further review of the literature showed that, despite some explorations of applying small-molecule multitargeted TKIs in the treatment of MPM, until today, no large series had a positive result. Anlotinib had been approved by the China Food and Drug Administration on treating non-small cell lung cancer, soft tissue sarcoma, renal cell carcinoma, and medullary thyroid cancer. We assumed that the ability of anlotinib to target more tyrosine kinase receptors than most of other TKIs could contribute to the long duration of PFS in this case, but further study is needed to further validate the efficacy of anlotinib in treatment of MPM.

The Relationship Between Perceptions of Leader Hypocrisy and Employees' Knowledge Hiding Behaviors: Testing a Moderated Mediation Model.

Purpose: Knowledge-sharing is critical for the survival and development of today's organization, but employees are not always willing to share their knowledge and sometimes even hide it intentionally or unintentionally. Taken from the leadership perspective, this paper aims to investigate the influence of leader hypocrisy on employees' knowledge-hiding behaviors. Drawing on the self-determination theory (SDT), this paper explores the mediating role of basic psychological needs satisfaction, as well as the moderating effect of employees' interdependent self-construal on the relationship between basic psychological needs satisfaction and knowledge-hiding behaviors. The moderated mediation effect is also tested. Methods: The data were collected from companies located in mainland China. The data sample for analysis consists of 336 employees. Hierarchical regression analysis was adopted to test the hypotheses of our proposed model. Results: Leader hypocrisy are positively related to knowledge-hiding behaviors (b = 0.490, p < 0.01). Basic psychological needs satisfaction plays a partial mediating role in such relationship (b =0.118, [0.056, 0.210]). The interdependent self-construal moderates the relationship between basic psychological needs satisfaction and knowledge-hiding behaviors (b = 0.134, p < 0.01), as well as the moderated mediation effect (BootSE = 0.018, [-0.083, -0.009]). Conclusion: The results show that leader hypocrisy is positively related to knowledge-hiding behaviors, and basic psychological needs satisfaction partially mediates such relationship. The interdependent self-construal weakens the negative relationship between basic psychological needs satisfaction and knowledge hiding.

Diffusion Path Identification of Public Opinion Involving Enterprise Green Technology Adoption: An Interpretive-Structural-Modeling-Based Approach.

With the increasing information transparency of business operations' environmental influences, public opinion plays an important role in the green technology adoption of enterprises. Identifying the diffusion path of public opinion involving the process of enterprise green technology adoption is a significant task to verify the triggering mechanisms among the external factors and internal ones. An appropriate framework may help to clarify how the sustainability elements of public opinion are introduced to green technology adoption. Therefore, an interpretive structural-modeling (ISM)-based approach was applied to explore the basic transmission process and path of public opinion involving green technology adoption in enterprise practices. From the pressure of public opinion to the stakeholders involved, as well as the corresponding operational environmental activities, this study explored the psychological behavior of internal and external stakeholders and tried to clarify what the driving elements of green technology adoption are and how they relate to each other. Based on the field data collected from practitioners with Chinese contextual experience, the driving elements of the enablers of green technology adoption by enterprises were identified, and the fundamental triggering mechanisms of the public opinion pressure among them were analyzed. Thereafter, the influence of internal and external stakeholders involving green technology adoption and their corresponding behaviors under the pressure of public opinion were determined and expounded comprehensively, which illustrates the diffusion path of how public opinion influences the operational green technology adoption. This may narrow the gap between public environmental expectation and business operations. Finally, the managerial implications and the limitations of this study were concluded. The explanatory corresponding ISM model established in this study enriches the literature on the theoretical research of the mechanisms of green technology adoption.

Curriculum Leadership of Rural Teachers: Status Quo, Influencing Factors and Improvement Mechanism-Based on a Large-Scale Survey of Rural Teachers in China.

Revealing the general status quo of teacher curriculum leadership has great theoretical, policy, and practical significance. However, large-scale empirical investigations in this area are rare, and there is even less attention to the current situation of rural teacher curriculum leadership. Based on the survey of 2,966 rural teachers in 20 provinces of China, this paper presented the status quo of rural teacher curriculum leadership and examined influencing factors through multiple linear regression analysis. It was found that curriculum leadership of rural teachers was at a low level with backward leadership views, lack of practical ability, and low sense of identity. Regression analysis demonstrated that individual field factors had a significant impact on teachers' curriculum leadership. Specifically, the higher the teachers' leadership willingness, trust in others, and self-efficacy, the higher the curriculum leadership. The school field was also an important influential aspect. In particular, the formation of a common vision and teacher community by the school and the appropriate empowerment of the principal had a significant positive impact on the curriculum leadership of rural teachers. Based on these key findings, several improvement suggestions are put forward at the end, which can be used as references for other countries to develop improvement plans on rural teacher curriculum leadership.

Multilayer Graphene Oxide Supported ZIF-8 for Efficient Removal of Copper Ions.

To address the performance deterioration of ZIF-8 for the adsorption of copper ions caused by powder volume pressure and particle aggregation, we employed multilayer graphene oxide (MGO) as a support to prepare composite adsorbents (MGO@ZIF-8) by using the in situ growth of ZIF-8 on MGO. Due to a good interfacial compatibility and affinity between ZIF-8 and graphene nanosheets, the MGO@ZIF-8 was successfully prepared. The optimal Cu2+ adsorption conditions of MGO@ZIF-8 were obtained through single factor experiments and orthogonal experiments. Surprisingly, the Cu2+ adsorption capacity was significantly improved by the integration of MGO and ZIF-8, and the maximum Cu2+ adsorption capacity of MGO@ZIF-8 reached 431.63 mg/g under the optimal adsorption conditions. Furthermore, the kinetic fitting and isotherm curve fitting confirmed that the adsorption law of Cu2+ by MGO@ZIF-8 was the pseudo-second-order kinetic model and the Langmuir isotherm model, which indicated that the process of Cu2+ adsorption was monolayer chemisorption. This work provides a new approach for designing and constructing ZIF-8 composites, and also offers an efficient means for the removal of heavy metals.

Histone deacetylation, as opposed to promoter methylation, results in epigenetic BIM silencing and resistance to EGFR TKI in NSCLC.

Drug resistance remains a major challenge in epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. Bcl-2-like protein 11 (BIM), a B-cell lymphoma 2 family pro-apoptotic protein, is a prime target for specific anti-cancer therapeutics. However, the epigenetic regulation of BIM in non-small cell lung cancer (NSCLC) cell lines and patients with NSCLC in association with EGFR-TKI resistance requires investigation. Methylation-specific PCR (MSP), pyrosequencing, and nested quantitative (q)-MSP were conducted to explore the methylation status of BIM in NSCLC cell lines. In addition, the methylation profile of BIM in patients with NSCLC was assessed by nested q-MSP using circulating free DNA. Cell lines, treated with methylation inhibitor 5-Aza-2'-deoxycytidine (AZA) or histone deacetylation inhibitor trichostatin A (TSA) prior to gefitinib treatment, were examined for BIM gene expression and resistance to gefitinib. All cell lines used in the present study presented with hypo-methylated BIM. Treatment with AZA had no effect on BIM RNA expression in PC9 cells or the gefitinib-resistant cell lines PC9/R and PC9/G2, nor did it reverse their resistance to gefitinib. In contrast, TSA treatment produced the opposite result. In the present study, 25 (78.1%) patients with hypo-methylated BIM and 7 patients (21.9%) with partial or hyper-methylated BIM were identified. The clinicopathological data revealed a random hypo-methylated BIM distribution amongst patients with NSCLC. In the overall study group and EGFR mutant group, hypo-methylated BIM carriers presented with no significant differences in progression free survival compared with patients with partial or hyper-methylated BIM. All cell lines in the present study and the majority of patients with NSCLC carried hypo-methylated BIM. Histone deacetylation, as opposed to promoter methylation, may contribute to the epigenetic silencing of BIM and lead to EGFR TKI resistance in NSCLC.

Percutaneous imaging-guided cryoablation for lung cancer.

Percutaneous cryoablation under imaging guidance has been proved to be a safe and effective method for ablation and debulking of tumors, providing radical cure or palliation, as the case may be, for patients with different stages of disease. The local control rate is high with cryoablation, and the complications are usually controllable, making it a reasonable choice in lung cancer treatment. In this paper the technique and mechanism of action of cryoablation are summarized, and studies performed on the application of percutaneous cryoablation in various stages of lung cancer are reviewed. Its emerging application in the treatment of pure ground-glass nodules (GGNs) is also introduced.

Hypoxia-induced cell stemness leads to drug resistance and poor prognosis in lung adenocarcinoma.

BACKGROUND: Since cancer stem cells exhibit embryonic-like self-renewal characteristics and malignant behavior, including drug resistance and metastasis, they may be the origin of tumorigenesis and cancer recurrence. Cancer cell stemness is also highly relevant to cancer in hypoxic environments. METHODS: In our study, we used cobalt dichloride (CoCl2) to create a hypoxic environment for lung adenocarcinoma A549 cells and the cisplatine-resistant cell line A549/DDP. The cancer stem-like CD166 positive population and the cells' stemness were detected by flowcytometry and quantitative real-time PCR after separation using magnetic antibodies. Drug resistance to cisplatine, docetaxel and pemetrexed was also measured. Finally, a tissue array was used to analyze the relationship between hypoxia-induced stemness and overall survival after radical surgery. RESULTS: Data showed that chemical-induced hypoxia changed cell stemness by enhancing stem cell transcription factors and markers of chemotherapeutic drug resistance. The CD166-positive cancer stem cell-like population showed greater drug resistance than the CD166-negative cells. Tissue array studies also suggested a poorer prognosis for patients whose tissue expressed higher CD166 levels. CONCLUSION: Our findings indicate that chemical hypoxia may augment cancer cell stemness and drug resistance in CD166-positive stem cells. Therefore, targeting the stem-like cell population, especially CD166-positive cells, may represent a novel therapeutic strategy to treat lung cancer.

Serum levels of the cancer-testis antigen POTEE and its clinical significance in non-small-cell lung cancer.

BACKGROUND: POTEE (POTE ankyrin domain family, member E) is a newly identified cancer-testis antigen that has been found to be expressed in a wide variety of human cancers including cancers of the colon, prostate, lung, breast, ovary, and pancreas. AIM: To measure the serum levels of POTEE in patients with non-small-cell lung cancer (NSCLC) and to explore the clinical significance of POTEE in NSCLC. PATIENTS AND METHODS: 104 NSCLC patients, 66 benign lung disease patients and 80 healthy volunteers were enrolled in this study from May 2013 to February 2014. Serum POTEE levels were measured using enzyme-linked immunosorbent assay (ELISA). Numerical variables were recorded as means ± standard deviation (SD) and analyzed by independent t tests. Categorical variables were calculated as rates and were analyzed using a χ2 test or Fisher's exact test. Survival curves were estimated and compared using the Kaplan-Meier method and log-rank tests. RESULTS: Serum POTEE levels were significantly higher in NSCLC patients than in benign lung disease patients and healthy controls (mean ± SD [pg/ml], 324.38± 13.84 vs. 156.93 ± 17.38 and 139.09 ± 15.80, P<0.001) and were significantly correlated with TNM stage. Survival analysis revealed that patients with low serum POTEE had longer progression-free survival (PFS) than those with high serum POTEE (P=0.021). Cox multivariate analysis indicated that POTEE was an independent prognostic factor of progression-free survival (P =0.009, hazard ratio, 2.440). CONCLUSIONS: Serum POTEE level in NSCLC patients is associated with TNM stage and is a potential prognostic factor.

Microarray expression profile of long non-coding RNAs in EGFR-TKIs resistance of human non-small cell lung cancer.

The application of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is limited by drug resistance in non-small cell lung cancer (NSCLC). Long non-coding RNAs (lncRNAs) are known to be involved in tumor development and metastasis, as well as chemotherapy resistance. To gain insight into the molecular mechanisms of EGFR-TKIs resistance, EGFR-TKIs­sensitive and ­resistant human lung cancer cells were analyzed by lncRNA microarray. In the present study, we found a total of 22,587 lncRNAs expressed in lung cancer cells. Of these, the expression level of 1,731 lncRNAs was upregulated >2-fold compared with gefitinib-sensitive cells while that of 2,936 was downregulated. Bioinformatics analysis (GO and pathway analyses) revealed that some classical pathways participating in cell proliferation and apoptosis were aberrantly expressed in these cells (P-value cut-off was 0.05). Enhancer-like lncRNAs and their nearby coding genes were analyzed. Six lncRNAs were identified as potential enhancers. Several lncRNAs were validated in lung cancer cell lines using RT-qPCR. To the best of our knowledge, the results showed for the first time that differentially expressed lncRNAs responded to EGFR-TKIs resistance in NSCLC cells. LncRNAs may therefore be novel candidate biomarkers and potential targets for EGFR-TKIs therapy in the future.

Long non-coding RNA UCA1 induces non-T790M acquired resistance to EGFR-TKIs by activating the AKT/mTOR pathway in EGFR-mutant non-small cell lung cancer.

The aim of this study was to explore the role of long non-coding RNA UCA1 (urothelial cancer-associated 1) in acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC). In our study, UCA1 expression was significantly increased in lung cancer cells and patients with acquired resistance to EGFR-TKIs. Over-expression of UCA1 was significantly associated with a shorter progression-free survival (PFS) [13.0 vs. 8.5 months, P < 0.01] in tumors with respond to EGFR-TKIs. The significant relationship was not observed in patients with T790M mutation (10.5 vs. 12.0 months, P = 0.778), but in patients with non-T790M (19.0 vs. 9.0 months, P = 0.023). UCA1 knockdown restored gefitinib sensitivity in acquired resistant cells with non-T790M and inhibited the activation of the AKT/mTOR pathway and epithelial-mesenchymal transition (EMT). The mTOR inhibitor was effective in UCA1-expressing cell PC9/R. Inhibiting mTOR could change the expression of UCA1, although there was no significant difference. In conclusion, the influence of over-expression of UCA1 on PFS for patients with acquired resistance to EGFR-TKIs was from the subgroup with non-T790M mutation. UCA1 may induce non-T790M acquired resistance to EGFR-TKIs by activating the AKT/mTOR pathway and EMT.

Detecting ALK, ROS1 and RET Fusion Genes in Cell Block Samples.

Whether Cell block (CB) samples are applicable to detect anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and ret proto-oncogene (RET) fusion genes in lung adenocarcinoma is still unknown. In this study, 108 cytological samples that contained lung adenocarcinoma cells were collected, and made into CB. The CB samples all contained at least 30% lung adenocarcinoma cells. In these patients, 48 harbored EGFR mutation. Among the 50 EGFR wild type patients who detected fusion genes, 14 carried EML4-ALK fusion (28%), 2 had TPM3-ROS1 fusion (4%), and 3 harbored KIF5B-RET fusion (6%). No double fusions were found in one sample. Patients with fusion genes were younger than those without fusion genes (p = 0.032), but no significant difference was found in sex and smoking status (p > 0.05). In the thirty-five patients who received first-line chemotherapy, patients with fusion gene positive had disease control rate (DCR) (72.7% VS 50%, p > 0.05) and objective response rate (ORR) (9.1% VS 4.2%, p > 0.05) compared with those having fusion gene negative. The median progression free survival (mPFS) were 4.0 and 2.7 months in patients harbored fusion mutations and wild type, respectively (p > 0.05). We conclude that CB samples could be used to detect ALK, ROS1 and RET fusions in NSCLC. The frequency distribution of three fusion genes is higher in lung adenocarcinoma with wild-type EGFR, compared with unselected NSCLC patient population. Patients with fusion genes positive are younger than those with fusion gene negative, but they had no significantly different PFS in first-line chemotherapy.

Peripheral blood for epidermal growth factor receptor mutation detection in non-small cell lung cancer patients.

OBJECTIVE: It is important to analyze and track Epidermal Growth Factor Receptor (EGFR) mutation status for predicting efficacy and monitoring resistance throughout EGFR-tyrosine kinase inhibitors (TKIs) treatment in non-small cell lung cancer (NSCLC) patients. The objective of this study was to determine the feasibility and predictive utility of EGFR mutation detection in peripheral blood. METHODS: Plasma, serum and tumor tissue samples from 164 NSCLC patients were assessed for EGFR mutations using Amplification Refractory Mutation System (ARMS). RESULTS: Compared with matched tumor tissue, the concordance rate of EGFR mutation status in plasma and serum was 73.6% and 66.3%, respectively. ARMS for EGFR mutation detection in blood showed low sensitivity (plasma, 48.2%; serum, 39.6%) but high specificity (plasma, 95.4%; serum, 95.5%). Treated with EGFR-TKIs, patients with EGFR mutations in blood had significantly higher objective response rate (ORR) and insignificantly longer progression-free survival (PFS) than those without mutations (ORR: plasma, 68.4% versus 38.9%, P = 0.037; serum, 75.0% versus 39.5%, P = 0.017; PFS: plasma, 7.9 months versus 6.1 months, P = 0.953; serum, 7.9 months versus 5.7 months, P = 0.889). In patients with mutant tumors, those without EGFR mutations in blood tended to have prolonged PFS than patients with mutations (19.7 months versus 11.0 months, P = 0.102). CONCLUSIONS: EGFR mutations detected in blood may be highly predictive of identical mutations in corresponding tumor, as well as showing correlations with tumor response and survival benefit from EGFR-TKIs. Therefore, blood for EGFR mutation detection may allow NSCLC patients with unavailable or insufficient tumor tissue the opportunity to benefit from personalized treatment. However, due to the high false negative rate in blood samples, analysis for EGFR mutations in tumor tissue remains the gold standard.

miR-200c overexpression is associated with better efficacy of EGFR-TKIs in non-small cell lung cancer patients with EGFR wild-type.

Several randomized trials have demonstrated non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations can achieve favorable clinical outcomes on treatment with EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation is considered as a predictive marker for efficacy of EGFR-TKIs in NSCLC. Here we show miR-200c overexpression was correlated with the epithelial phenotype and sensitivity to gefitinib in EGFR wild-type NSCLC cell lines. Up-regulated miR-200c could regain the sensitivity to gefitinib in the EGFR wild-type cell lines and miR-200c could regulate epithelial to mesenchymal transition through PI3K/AKT and MEK/ERK pathways. NSCLC patients at advanced stage (N=150) who received EGFR-TKIs (gefitinib or erlotinib) as second- or third-line therapy from September 2008 to December 2012 were included in the study. In 66 NSCLC patients with wild-type EGFR, high levels of miR-200c expression was associated with higher disease control rate (DCR), longer progression-free survival (PFS) and longer overall survival (OS) compared with low miR-200c expression subgroup. In the subgroup with EGFR mutation, the trend remained the same but not statistically significant. Overall, these findings indicated that miR-200c might be a predictive biomarker for sensitivity to EGFR-TKIs in advanced NSCLC patients with wild-type EGFR.