Survival Time Of Non-small Cell Lung Cancer Patients Research Articles

The value of EGFR in individualized treatment for brain metastases in non-small cell lung cancer

The prognosis of brain metastases in non-small cell lung cancer (NSCLC) is poor, and patients with EGFR mutations are more likely to have brain metastases. The epidermal growth factor receptor (EGFR) gene status has changed the direction of treatment for NSCLC patients with brain metastases. The development of EGFR tyrosine kinase inhibitors (EGFR-TKI) has prolonged the survival time of NSCLC patients with brain metastases. The treatment of patients with NSCLC brain metastases should be individualized according to the clinical symptoms, tumor stage, and different gene mutation status. As cancer is heterogeneous at the molecular level, related biomarker studies looking for individualized characteristics are recommended.

The influence of anti-cancer therapies on lymphocyte subpopulations of lung cancer patients.

There are limited data on the influence of different anti-cancer therapies on lymphocyte subpopulations and their relationships to survival of non-small cell lung cancer (NSCLC) patients. This study aimed to assess the effect of immunotherapy, chemotherapy, immunochemotherapy, adjuvant chemotherapy after surgery, and antibodies against Vascular Endothelial Growth Factors (VEGF) on B cell, T cell, and NK cell subpopulations, and the survival time of NSCLC patients. A total of 32 consecutive NSCLC patients were recruited at Pulmonology Clinic, Leipzig from January 2018 to March 2020 and enrolled in this study. Immunophenotyping was done using a FACS Canto II flow cytometer (BD Biosciences) before the administration of the planned therapy and during therapy with up to 7 observational windows for each patient targeting 130 immunologic parameters. Absolute transitional B cells was significantly increased after immunotherapy (p = 0.032), immunochemotherapy (p = 0.030), and antibodies against VEGF (p = 0.024). Similarly, absolute counts and percentage of B cells were significantly increased after adjuvant chemotherapy (p = 0.023). However, absolute counts and percentage of transitional B cells are significantly decreased after chemotherapy (p = 0.001). Activated cytotoxic T cells were significantly increased after immunotherapy (p = 0.031) and immunochemotherapy (p = 0.030). The overall survival rate of NSCLC patients was 31%. In conclusion, this study suggests that different types of anti-cancer therapies affect lymphocyte subpopulations of NSCLC patients. Further large-scale and multicentre studies are required to confirm our results and to evaluate the prognostic value of lymphocyte subpopulations.

GNIP1 functions both as a scaffold protein and an E3 ubiquitin ligase to regulate autophagy in lung cancer

BackgroundGlycogen-Interacting Protein 1 (GNIP1), an E3 ligase, is a member of the tripartite motif (TRIM) family proteins. Current studies on GNIP1 mainly focus on glycogen metabolism. However, the function and molecular mechanisms of GNIP1 in regulating autophagy still remains unclear. This study aimed to investigate the regulatory mechanism of GNIP1 in regulating autophagy in non-small cell lung cancer (NSCLC).MethodsCrystal violet staining assays were used to evaluate the ability of cell growth and proliferation. Transwell and scratch wound healing assays were used to evaluate the cell migration ability. The protein expressions were measured by western blot and immunohistochemistry. Co-immunoprecipitation assays determined the protein–protein interactions. The in vivo effect of GNIP1 on tumor growth was determined by xenograft assay.ResultsWe found that GNIP1 was overexpressed in tumor tissues and the expression level of GNIP1 was related to the poor prognosis and the survival time of NSCLC patients. In non-small cell lung cancer (NSCLC), GNIP1 increased proliferation and migration of cancer cells by promoting autophagy. Mechanistic studies indicated that GNIP1, as a scaffold protein, recruited BECN1 and LC3B to promote the formation of autophagosomes. Besides, GNIP1 mediated the degradation of 14-3-3ζ, the negative regulator of VPS34 complex, thus promoting autophagy. Overexpressing GNIP1 promoted tumorigenesis and enhanced autophagy in xenograft models.ConclusionGNIP1 promotes proliferation and migration of NSCLC cells through mediating autophagy, which provides theoretical basis for targeting GNIP1 as anti-cancer drugs.53EaKE_BNMRSjuuBW6dyKUVideo

Research Progress on Risk Factors of Brain Metastasis in Non-small Cell Lung Cancer

非小细胞肺癌（non-small cell lung cancer, NSCLC）脑转移是常见的治疗失败模式，发生脑转移的NSCLC患者中位生存时间仅为1个月-2个月。预防性脑照射（prophylactic cranial irradiation, PCI）可延缓脑转移的发生，但对NSCLC患者的生存获益仍存在争议，因此，通过预测脑转移的风险筛选可能从PCI中获益的人群尤为重要。本文就NSCLC脑转移的高危因素进行综述。

A nomogram model based on peripheral blood lymphocyte subsets to assess the prognosis of non-small cell lung cancer patients treated with immune checkpoint inhibitors.

BackgroundThe primary aim of this study was to investigate the prognostic value of peripheral blood lymphocyte subsets in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs).MethodsFrom 2018 to 2019, 82 patients diagnosed with stage IIIB–IV NSCLC at Zhejiang Cancer Hospital were recruited for this study. Peripheral blood lymphocyte subsets of NSCLC patients were analyzed using flow cytometry before and after ICI treatment. The relationship between the percentage of peripheral blood lymphocyte subsets, clinicopathological features, progression-free survival (PFS), and overall survival (OS) was identified by correlation heat map, Kaplan-Meier curve, log-rank test, and Cox regression analysis.ResultsThe CD4/CD8 ratio and the percentage of B cells was decreased after ICI treatment. Furthermore, the percentage of CD3+ T cells, natural killer (NK) cells, and natural killer T (NKT) cells before ICI treatment was associated with brain metastases, the proportion of CD3+CD4+ T cells before ICI treatment was related to epidermal growth factor receptor (EGFR) status, the CD4/CD8 ratio before ICI treatment was correlated to pathology, the ratio of B cells before ICI treatment was related to therapeutic regimen, and the percentage of NKT cells before ICI treatment was associated with use of radiotherapy. Furthermore, univariate survival analysis revealed that low percentage of B cells forecasted a poor OS for NSCLC patients with ICI treatment. In addition, the nomogram developed by percentages of peripheral blood lymphocyte subsets could determine survival probability and survival time of NSCLC patients with immunotherapy.ConclusionsICI treatment induced changes in the percentage of peripheral blood lymphocyte subsets, which had prognostic value for brain metastases, radiotherapy, EGFR status, pathology, and therapeutic regimen, along with prognostic value, for NSCLC patients treated with ICIs.

Construction of a prognostic model for non-small-cell lung cancer based on ferroptosis-related genes.

We wished to construct a prognostic model based on ferroptosis-related genes and to simultaneously evaluate the performance of the prognostic model and analyze differences between high-risk and low-risk groups at all levels. The gene-expression profiles and relevant clinical data of patients with non-small-cell lung cancer (NSCLC) were downloaded from public databases. Differentially expressed genes (DEGs) were obtained by analyzing differences between cancer tissues and paracancerous tissues, and common genes between DEGs and ferroptosis-related genes were identified as candidate ferroptosis-related genes. Next, a risk-score model was constructed using univariate Cox analysis and least absolute shrinkage and selection operator (Lasso) analysis. According to the median risk score, samples were divided into high-risk and low-risk groups, and a series of bioinformatics analyses were conducted to verify the predictive ability of the model. Single-sample gene set enrichment analysis (ssGSEA) was used to investigate differences in immune status between high-risk and low-risk groups, and differences in gene mutations between the two groups were investigated. A risk-score model was constructed based on 21 ferroptosis-related genes. A Kaplan–Meier curve and receiver operating characteristic curve showed that the model had good prediction ability. Univariate and multivariate Cox analyses revealed that ferroptosis-related genes associated with the prognosis may be used as independent prognostic factors for the overall survival time of NSCLC patients. The pathways enriched with DEGs in low-risk and high-risk groups were analyzed, and the enriched pathways were correlated significantly with immunosuppressive status.

SP1-induced overexpression of LINC00520 facilitates non-small cell lung cancer progression through miR-577/CCNE2 pathway and predicts poor prognosis.

Long noncoding RNAs (lncRNAs) have gained much attention in the past few years. Long intergenic non-protein coding RNA 520 (LINC00520) was one of the newly discovered lncRNA which has been demonstrated to be dysregulated in several cancers. So far, the function and mechanism of LINC00520 in non-small cell lung cancer (NSCLC) are unclear. In this paper, our group first showed that LINC00520 level was elevated in non-small cell lung cancer (NSCLC) tissue and cells. In addition, SP1 could bind directly to the promoter region of LINC00520 and thus promote its transcription. Increased LINC00520 was distinctly correlated with advanced tumor stage and shorter survival time in NSCLC patients. Further functional investigations provided evidences that forced down regulation of LINC00520 inhibited NSCLC cell proliferation, invasion, metastasis and EMT, while contributing to cells apoptosis. Mechanistically, we found that LINC00520 serving as a competing endogenous RNA to be involved in the modulation of miR-577 expressions, and thus affected the expression of CCNE2 which was a target gene of miR-577. Moreover, in NSCLC cells with si-LINC00520, up regulation of CCNE2 led to an increase of cell growth and invasion. Taken together, LINC00520 displayed its tumor-promotive roles through modulating the miR-577/CCNE2 axis, highlighting a potential therapeutic strategy for NSCLC patients.

Changes in serum inflammatory factors, adiponectin, intestinal flora and immunity in patients with non-small cell lung cancer.

The aim of this study was to explore the changes in the body state of patients with non-small cell lung cancer (NSCLC), including intestinal flora, serum inflammatory factors, immunity and adiponectin. A total of 18 NSCLC patients (disease group) and 16 healthy people from the Medical Center (control group) were selected as research objects. The levels of immune molecules immunoglobulin A (IgA), IgG and IgM, and inflammatory factors interleukin-2 (IL-2), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and IL-6 were detected via enzyme-linked immunosorbent assay (ELISA). The level of adiponectin was determined using the quantitative kit. In addition, the changes in intestinal flora were analyzed. The overall survival time of NSCLC patients was significantly affected by IL-2 (p=0.0026), CRP (p=0.03), TNF-α (p=0.014) and IL-6 (p=0.00018). It can be seen that these inflammatory factors may play important roles in the progression of NSCLC. The levels of TNF-α (p=0.037), IL-2 (p=0.043) and CRP (p=0.000) in the peripheral blood serum were significantly higher in disease group than control group. Meanwhile, the levels of IgA (p=0.040) and IgG (p=0.000) in the peripheral blood serum were significantly higher in disease group than control group. However, no significant difference was observed in the level of IgM between the two groups (p>0.05). The expression of adiponectin gene (ADIPOQ) could remarkably affect the overall survival rate of NSCLC patients, and patients with high expression of ADIPOQ exerted significantly better prognosis (p=0.017). The level of serum adiponectin was evidently higher in control group than that in disease group (p<0.05). According to the linear discriminant analysis (LDA) score of the intestinal flora in both groups, the abundance of some intestinal flora (Enterobacter and Lachnospiraceae) was markedly higher in disease group than control group (p<0.05). However, the abundance of Bifidobacteria, Pediococcus and Lactobacillus was remarkably higher in control group than disease group (p<0.05). Correlation analysis indicated that Lactobacillus was positively correlated with Bifidobacteria (r=0.44, p=0.000), whereas was negatively correlated with Enterobacter (r=-0.22, p=0.024). Furthermore, Enterobacter was negatively associated with Bifidobacteria (r=-0.15, p=0.038) and Streptococcus (r=-0.12, p=0.046). Serum inflammatory factors, adiponectin, intestinal flora and immunity may play important roles in the development of NSCLC.

P53 Affects PGC1α Stability Through AKT/GSK-3β to Enhance Cisplatin Sensitivity in Non-Small Cell Lung Cancer.

Drug resistance greatly limits the therapeutic efficacy of treatment of non-small cell lung cancer (NSCLC). One of the important factors is the dysfunction of tumor suppressor p53. Recent studies have suggested that p53 suppresses tumors by regulating number of mitochondrial proteins, including peroxisome proliferator-activated receptor coactivator (PGC1α). Although several studies have confirmed the interaction between p53 and PGC1α, the precise mechanism has not been completely determined in NSCLC. In this study, we investigated the specific signaling between p53 and PGC1α to improve anti-tumor drug effects on NSCLC. We found that low expression of p53 and high expression of PGC1α correlated with shorter survival time of NSCLC patients. In vitro experiments confirmed that NCI-H1299 (p53-null) cells had high levels of PGC1α and were insensitive to cisplatin (CDDP). When PGC1α was knocked down, the sensitivity to cisplatin was increased. Notably, the stability of PGC1α is an important mechanism in its activity regulation. We demonstrated that p53 decreased the stability of PGC1α via the ubiquitin proteasome pathway, which was mediated by protein kinase B (AKT) inhibition and glycogen synthase kinase (GSK-3β) activation. Therefore, p53 may regulate the stability of PGC1α through the AKT/GSK-3β pathway, thus affect the chemosensitivity of NSCLC.

Upregulation of microRNA-1303 is a potential prognostic marker of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the major subtype of lung cancer, imposing a huge disease burden worldwide. MicroRNA-1303 (miR-1303) has been demonstrated to be involved in several diseases, including cancers. In this study, we aimed to investigate the role of miR-1303 in NSCLC. We quantified the expression levels of miR-1303 in NSCLC tissues and cells using the qRT-PCR assay. Then the association between miR-1303 expression and clinical characteristics of patients was analyzed using the χ2 test. The Kaplan-Meier and multivariate Cox regression assays were used to investigate the prognostic value of miR-1303 in NSCLC. Furthermore, the functional proliferation, migration, and invasion assays were used to explore the miR-1303 functions in vitro. The expression of miR-1303 was upregulated in NSCLC tissue samples and cells. The upregulation of miR-1303 was associated with TNM stage and lymph node metastasis. The survival time of NSCLC patients with high expression of miR-1303 was shorter than those with low expression. The functional analyses revealed that overexpression of miR-1303 in H1299 and A549 cells promoted cell proliferation, migration, and invasion. These results suggest that miR-1303 may be a potential prognostic biomarker for NSCLC and be involved in the progression of NSCLC.

MiR-181a reduces radiosensitivity of non-small-cell lung cancer via inhibiting PTEN.

The aim of this study is to explore the effect of micro ribonucleic acid (miR)-181a on the radiosensitivity of non-small cell lung cancer (NSCLC) and its potential mechanism of action. The differentially expressed miRNAs were screened in lung cancer tissues of radiotherapy-resistant and non-radiotherapy-resistant NSCLC patients, and verified via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Next, the effects of different miRNA expressions on patients' survival time were discussed, and target genes of miR-181a were predicted. The effect of miR-181a expression on radiosensitivity was determined using cell counting kit-8 (CCK-8) assay and flow cytometry. The direct target of miR-181a was verified via luciferase reporter assay. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) was overexpressed using lentiviruses, and then whether miR-181a reduces radiosensitivity via targeting PTEN was detected via CCK-8 assay and flow cytometry. Finally, Western blotting was performed to detect the protein expression of PTEN. The screening results of microarray expression profile assay revealed that 15 miRNAs had significant differences in lung cancer tissues of radiotherapy-resistant NSCLC patients compared with those in non-radiotherapy-resistant NSCLC patients. The results of RT-qPCR showed that hsa-miR-181a, hsa-miR-199b, hsa-miR-489 and hsa-miR-589 were significantly up-regulated in the lung cancer tissues of radiotherapy-resistant NSCLC patients compared with those in non-radiotherapy-resistant NSCLC patients. In addition, it was found that the survival time of NSCLC patients was obviously prolonged in hsa-miR-181a low-expression group and hsa-miR-589 high-expression group, but hsa-miR-489 and hsa-miR-199b had no significant influence on the survival time of NSCLC patients. According to KEGG enrichment analysis, the target genes of miR-181a were evidently enriched in the phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (AKT) signaling pathway, NSCLC signaling pathway and other cancer signaling pathways. Under the radiation dose of 2, 4, 6 and 8 Gy, the survival rate of A549 cells rose in miR-181a mimic group, but declined in miR-181a inhibitor group. Moreover, compared with that in model group, the radiotherapy-induced apoptosis was markedly inhibited in miR-181a mimic group, but markedly promoted in miR-181a inhibitor group. It was also observed that the response of cells to radiotherapy-induced apoptosis was remarkably weakened in miR-181a mimic + PTEN overexpression group compared with that in miR-181a mimic group. Finally, miR-181a mimic group had a significantly lower protein expression of PTEN and significantly higher protein expressions of CXC chemokine receptor 4 (CXCR4), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), p-AKT1 and p-mammalian target of rapamycin (mTOR) than model group, while miR-181a inhibitor group had the opposite protein expressions. The protein expressions of CXCR4, p-STAT3, p-AKT1 and p-mTOR were obviously lower in miR-181a mimic + PTEN overexpression group than those in miR-181a mimic group. MiR-181a reduces the radiosensitivity of NSCLC via inhibiting PTEN expression.

Overexpression of HSP10 correlates with HSP60 and Mcl-1 levels and predicts poor prognosis in non-small cell lung cancer patients.

BACKGROUND: HSP60 and its partner HSP10 are members of heat shock proteins (HSPs) family, which help mitochondrial protein to fold correctly. Mcl-1, a member of the Bcl-2 family, plays a crucial role in regulation of cell apoptosis. Aberrant expression of HSP10, HSP60 and Mcl-1 is involved in the development of many tumors.OBJECTIVE: To examine the association between expression of HSP10, HSP60 and Mcl-1 and clinicopathological features of non-small cell lung cancer (NSCLC).METHODS: Tissue microarrays including 53 non-cancerous lung tissues (Non-CLT) and 354 surgically resected NSCLC were stained with anti-HSP10, anti-HSP60 and anti-Mcl-1 antibodies respectively by immunohistochemistry.RESULTS: Higher expression of HSP10, HSP60 and Mcl-1 was found in NSCLC compared with Non-CLT. Both individual and combined HSP10 and HSP60 expression in patients with clinical stage III was higher than that in stage I II. Expression of HSP10 showed a positive correlation with HSP60 and Mcl-1. Overall survival time of NSCLC patients was remarkably shorter with elevated expression of HSP10, HSP60 and Mcl-1 alone and in combination. Moreover overexpression of HSP10 and Mcl-1 was poor independent prognostic factor for lung adenocarcinoma patients.CONCLUSIONS: High expression of HSP10, HSP60 and Mcl-1 might act as novel biomarker of poor prognosis for NSCLC patients.

The novel lncRNA PTTG3P is downregulated and predicts poor prognosis in non-small cell lung cancer.

IntroductionLung cancer is the leading cause of cancer-associated mortality worldwide. Recently, long non-coding RNAs (lncRNAs) have been studied as key regulators in some biological processes. Of note, the molecular mechanism and prognostic value of lncRNAs in non-small cell lung cancer (NSCLC) have largely remained unclear.Material and methodsIn this study, we compared the PTTG3P expression levels between lung cancer and normal lung samples by analyzing 5 public datasets (GSE18842, GSE19804, GSE27262, GSE30219, and GSE19188). Next, pentose phosphate pathway and co-expression networks were constructed to identify key targets of lncRNA PTTG3P. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore the potential roles of lncRNA PTTG3P. Moreover, we constructed PTTG3P-mediated ceRNA networks in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC).ResultsIn the present study, our analysis showed that PTTG3P expression was higher in high T stage LUAD and LUSC samples, as well as high N stage NSCLC tissues. Of note, we found that higher PTTG3P expression is correlated with shorter survival time in NSCLC patients by analyzing Kaplan-Meier plotter datasets. We found that PTTG3P was significantly associated with NSCLC cell proliferation regulation by affecting a series of cell cycle related biological processes.ConclusionsBioinformatics analysis showed that PTTG3P was associated with NSCLC cell proliferation. These results suggested that PTTG3P could serve as a new therapeutic and prognostic target for NSCLC.

Downregulation of SRPK2 promotes cell cycle arrest though E2F1 in non-small cell lung cancer.

Serine-arginine protein kinase (SRPK) belongs to a class of cell cycle regulating kinases that can phosphorylate proteins containing serine/arginine-Rich (SR) regions. SR proteins are a family of RNAbinding phosphoproteins that control both constitutive and alternative pre-mRNA splicing events. However, little is known about their role in non-small cell lung cancer (NSCLC). In the present study, we found that serine-arginine protein kinase 2 (SRPK2) expression was upregulated in NSCLC tissues compared with adjacent normal tissues. Kaplan-Meier curve analyses showed that the overall survival time of NSCLC patients with high SRPK2 expression was shorter than those with low SRPK2 expression. Overexpression of SRPK2 promoted NSCLC cell proliferation and cell cycle arrest, while knockdown of SRPK2 inhibited proliferation and promoted cell cycle arrest in NSCLC cell lines. SRPK2 promoted the transcriptional regulation of E2F1 on downstream cell cycle related genes through phosphorylation of SC35. Xenograft model showed that SRPK2 promoted tumor growth in vivo. SRPK2 phosphorylated SC35 and phosphorylated SC35 activated E2F1 transcription of cyclin-related proteins, thereby promoting the cycle progression of NSCLC. Our findings demonstrated that SRPK2 may be a potential therapeutic target for NSCLC clinical therapy, which plays an important role in the progression of NSCLC.

EP1.16-44 Survival and Prognostic Association of Non-Small Cell Lung Cancer with Brain Metastases After WBRT: A Multicentre Study

Forty percent of intracranial tumors are metastatic, arising most commonly from lung. To our knowledge, no data is available on prognosis factors of the survival of non-small cell lung cancer (NSCLC) patients with brain metastases in Bangladesh. This study aims to determine overall survival (OS) and identify prognosis factors in NSCLC patients with brain metastases after whole brain radiation therapy (WBRT). The study retrospectively investigated histologically proven NSCLC patients with brain metastases at two tertiary hospitals in Bangladesh from January, 2013 to April, 2018. A total of 62 patients were eligible who received 30 Gy (3 Gy per fraction) of WBRT. The primary end point was OS and the secondary endpoint was prognostic association with various factors including patient age and gender, tumor histology, Karnofsky performance status, pleural effusion, primary not controlled, extracranial metastases, the number of brain metastases, surgical resection and diagnosed initially with brain metastases or developed brain metastases later. RTOG Recursive Partitioning Analysis (RPA) was used to categorize the patients. Survival was calculated by Kaplan-Meier method and compared by Log-rank test. Prognostic association was evaluated with Cox proportional hazards model analysis. Mean survival of the entire cohort was 5.76 months (95% CI: 4.69 – 6.84 months). Patients with brain metastases at diagnosis or developed brain metastases later during disease progression had a statistically similar mean survival (6.18 months vs. 5.49 months; P = 0.422). Among the 62 patients, 16.1%, 30.6% and 53.2% were RPA Class I, II and III respectively. Mean survival differed significantly among the three classes (Class I: 9.10 months, Class II: 6.68 months, Class III: 3.64 months; P = 0.00). Individual prognostic factors were not found to be associated with survival difference except, single vs. multiple brain metastases (P = 0.042) and primary controlled or not (P = 0.026). The study reported survival time of NSCLC patients with brain metastases undergo WBRT, and indicated that higher RPA classes, primary not controlled and greater numbers of brain metastatic lesions are the three prognostic factors of poor survival for this cohort. Our results may help clinicians in patient counseling, treatment selection and designing future clinical trials.

Molecular Mechanisms and Targeted Therapies Including Immunotherapy for Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer death worldwide. Molecular targeted therapy has greatly advanced the field of treatment for non-small cell lung cancer (NSCLC), which accounts for the majority of lung cancers. Indeed, gefitinib, which was the first molecular targeted therapeutic agent, has actually doubled the survival time of NSCLC patients. Vigorous efforts of clinicians and researchers have revealed that lung cancer develops through the activating mutations of many driver genes including the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), v-Raf murine sarcoma viral oncogene homolog B (BRAF), and rearranged during transfection (RET) genes. Although ALK, ROS1, and RET are rare genetic abnormalities, corresponding tyrosine kinase inhibitors (TKIs) can exert dramatic therapeutic effects. In addition to anticancer drugs targeting driver genes, bevacizumab specifically binds to human vascular endothelial growth factor (VEGF) and blocks the VEGF signaling pathway. The VEGF signal blockade suppresses angiogenesis in tumor tissues and inhibits tumor growth. In this review, we also explore immunotherapy, which is a promising new NSCLC treatment approach. In general, antitumor immune responses are suppressed in cancer patients, and cancer cells escape from the immune surveillance mechanism. Immune checkpoint inhibitors (ICIs) are antibodies that target the primary escape mechanisms, immune checkpoints. Patients who respond to ICIs are reported to experience longlasting therapeutic effects. A wide range of clinical approaches, including combination therapy involving chemotherapy or radiation plus adjuvant therapy, are being developed.

Long non-coding RNA MIAT promotes non-small cell lung cancer progression by sponging miR-1246.

Recently, long non-coding ribonucleic acids (lncRNAs) have attracted more attention for their roles in tumor progression. The aim of this study was to investigate the exact role of lncRNA MIAT in the progression of non-small cell lung cancer (NSCLC) and to explore the possible underlying mechanism. MIAT expression in NSCLC tissue samples was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The association between the expression of MIAT and the prognosis of NSCLC patients were explored. Furthermore, the wound healing assay and the transwell assay were conducted in vitro. In addition, the luciferase assay and the RNA immunoprecipitation assay (RIP) were used to elucidate the underlying mechanism. The MIAT expression in NSCLC tissues was significantly higher than that of the corresponding normal tissues. Meanwhile, the MIAT expression was associated with the overall survival time of NSCLC patients. The migration and invasion of cells were significantly promoted after MIAT was over-expressed in vitro. Meanwhile, the cell migration and cell invasion were obviously remarkedly inhibited after MIAT knock-down in vitro. Bioinformatics analysis predicted that microRNA-1246 (miR-1246) was as a novel target for MIAT. The expression of miR-1246 was significantly down-regulated or up-regulated after the overexpression or down-expression of MIAT, respectively. Further mechanism assays showed that miR-1246 was a direct target of MIAT in NSCLC. MIAT enhanced the NSCLC cell migration and invasion via targeting miR-1246, which might be a potential biomarker in NSCLC.

The serum level of CC chemokine ligand 18 correlates with the prognosis of non-small cell lung cancer.

CC chemokine ligand 18 (CCL18) is a chemotactic cytokine involved in the pathogenesis and progression of various cancers. Our previous research showed that the expression of CCL18 is obviously higher in non-small cell lung cancer (NSCLC) than in the adjacent normal tissues, suggesting its role in NSCLC. We further examined the serum level of CCL18 in 80 NSCLC patients with enzyme-linked immunosorbent assay and simultaneously analyzed the survival curve of these patients by the Kaplan-Meier method, and then utilized a log-rank test to evaluate the correlation of CCL18 expression with the malignant progression of NSCLC. Our results showed that the median serum concentration of CCL18 was significantly elevated to 436.11 ng/mL in NSCLC patients compared to 41.97 ng/ml in healthy people (P<0.01), which was also positively related to the expression of lung cancer biomarkers carcinoma-embryonic antigen and cytokeratin fragment antigen 21-1. Moreover, correlation analysis showed that an increased level of serum CCL18 was associated with a worse survival time in NSCLC patients. Our findings suggest that the serum CCL18 level of NSCLC patients was negatively correlated with the prognosis, thus suggesting that CCL18 may serve as a potential circulating biomarker for NSCLC diagnosis.

Long noncoding RNA DSCAM-AS1 functions as an oncogene in non-small cell lung cancer by targeting BCL11A.

Long noncoding RNAs (lncRNAs) have attracted more attention for their role in tumor progression recently. The aim of this study was to investigate the role of DSCAM-AS1 in the progression of non-small cell lung cancer (NSCLC), and to elucidate its possible underlying mechanism. DSCAM-AS1 expression in both NSCLC cells and tissue samples was detected by Real Time quantitative-Polymerase Chain Reaction (RT-qPCR). Moreover, the association between the DSCAM-AS1 expression level and patients' overall survival rate was explored. Furthermore, wound healing assay and transwell assay were conducted. In addition, RT-qPCR and Western blot assay were used to elucidate the underlying mechanism. DSCAM-AS1 expression level in NSCLC samples was significantly higher than that of the corresponding normal tissues. The expression level of DSCAM-AS1 was associated with an overall survival time of NSCLC patients. Besides, the migration and invasion abilities of NSCLC cells were remarkably promoted after DSCAM-AS1 overexpression in vitro. Moreover, the mRNA and protein expression of BCL11A was significantly upregulated after the overexpression of DSCAM-AS1. Furthermore, the expression of BCL11A was positively correlated with DSCAM-AS1 expression in NSCLC tissues. We observed that DSCAM-AS1 could enhance NSCLC cell migration and invasion via upregulating BCL11A. Furthermore, DSCAM-AS1 might be a potential therapeutic target for NSCLC.

MiRNA-195-5p Functions as a Tumor Suppressor and a Predictive of Poor Prognosis in Non-small Cell Lung Cancer by Directly Targeting CIAPIN1

Accumulating evidence suggests that microRNAs (miRNAs) has been proven to be a critical regulator in the tumor progression, of which miR-195-5p was reported to function as tumor suppressor in prostate cancer and oral squamous cell carcinoma. However, studies on the clinical significance and biological function of miR-195-5p in non-small cell lung cancer (NSCLC) were still unavailable. Here, we reported that the expression of miR-195-5p was decreased in NSCLC tissues and cell lines. Downregulation of miR-195-5p was significantly associated with TNM stage, tumor size and lymph node metastasis. The Kaplan-Meier survival analysis demonstrated that the survival time of NSCLC patients with high expression of miR-195-5p was longer than those with low expression during the 5-year follow up period (p = 0.0410). COX regression analysis indicated that miR-195-5p expression was an independent prognostic indicator for the survival of NSCLC patients (HR = 2.45, 95% CI: 1.53–4.63; p = 0.007). Results of functional analyses revealed that overexpression of miR-195-5p in A549 cells inhibited cell proliferation, induced cell cycle G0/G1 phase arrest and apoptosis using MTT and flow cytometry analysis. Furthermore, bioinformatics and luciferase reporter assays demonstrated that cytokine-induced apoptosis inhibitor 1 (CIAPIN1), an anti-apoptotic molecule was a direct target of miR-195-5p in NSCLC cells. Meta-analysis based on Oncomine database showed CIAPIN1 was significantly up-regulated in human lung cancer tissues. Consistently, knockdown of CIAPIN1 phenocopied the inhibitory effects of miR-195-5p overexpression in NSCLC cell function. These findings suggest that miR-195-5p could be used as a potential prognostic predictor and tumor suppressor in NSCLC.