Comprehensive Analysis of Competing Endogenous RNA (ceRNA) Network Based on RNAs Differentially Expressed in Lung Adenocarcinoma Using The Cancer Genome Atlas (TCGA) Database.
利用癌症基因组图谱 (TCGA) 数据库综合分析肺腺癌中差异表达的 RNA 的竞争性内源性 RNA (ceRNA) 网络。
- 作者列表："Tang H","Wang Z","Shao Q","Wang Y","Yang Q
:BACKGROUND The aim of this study was to explore a comprehensive analysis of the competing endogenous (ceRNA) network of lung adenocarcinoma and predict its regulatory mechanism and prognosis correlation based on The Cancer Genome Atlas (TCGA) database. MATERIAL AND METHODS The genes expression data from 535 lung adenocarcinoma cases and 59 normal tissue cases were acquired and downloaded from TCGA database, and differentially expressed messenger RNA (mRNA), long noncoding RNA (lncRNA) and microRNA (miRNA) were selected primarily by "edgeR" package in R software, which further constructs lncRNA-miRNA-mRNA ceRNA network. We then proceed to carry out Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Kaplan-Meier survival analysis of the mRNAs involved in the ceRNA network. RESULTS There are 3 mRNAs (ANLN, IGFBP1, and TFAP2A) in differentially expressed genes, 4 lncRNAs (AC015923.1, FGF12-AS2, LINC00211, and MED4-AS1), and 2 miRNAs (miR-31 and miR-490) associated with the prognostic of lung adenocarcinoma. Besides, LINC00461 and has-mir-139 as key nodes were found in the ceRNA network. Significantly, miR-31 shows the greatest prognostic value related to the adverse effect of the prognostic of lung adenocarcinoma (P<0.001). CONCLUSIONS By analyzing the expression data of lung adenocarcinoma in TCGA database, we found that 3 mRNAs, 4 lncRNAs, and 2 miRNAs were screened as potential prognostic factors for lung adenocarcinoma. In addition, LINC00461 and has-mir-139 are 2 important regulatory network nodes in lung adenocarcinoma ceRNA.
背景: 本研究的目的是探索竞争性内源性 (ceRNA) 的综合分析。基于癌症基因组图谱 (TCGA) 数据库的肺腺癌网络及其预测调控机制和预后相关性。材料和方法从 TCGA 数据库中获取并下载 535 例肺腺癌病例和 59 例正常组织的基因表达数据，以及差异表达的信使 RNA (mRNA) 、长链非编码 RNA (lncRNA) 和 microRNA (miRNA) 主要通过 R 软件中的 “edgeR” 包选择,这进一步构建了 lncRNA-miRNA-mRNA ceRNA 网络。然后我们着手进行基因本体富集分析，京都基因和基因组百科全书 (KEGG) 通路分析，以及涉及 ceRNA 网络的 mRNAs 的 Kaplan-Meier 生存分析。结果差异表达基因中有 3 个 mRNAs (ANLN 、 IGFBP1 和 TFAP2A)，4 个 lncRNAs (AC015923.1 、 FGF12-AS2 、 LINC00211 和 MED4-AS1) 和 2 个 miRNAs (miR-31 和 miR-490) 与肺腺癌的预后相关。此外，LINC00461 和 has-mir-139 作为 ceRNA 网络中的关键节点。MiR-31 对肺腺癌预后的影响最大 (P<0.001)。结论通过分析 TCGA 数据库中肺腺癌的表达数据，我们发现 3 个 mRNAs 、 4 个 lncRNAs 和 2 个 miRNAs 被筛选为肺腺癌的潜在预后因子。此外，LINC00461 和 has-mir-139 是肺腺癌 ceRNA 中的 2 个重要调控网络节点。
METHODS:BACKGROUND:The objectives of this study are to assess the chest drainage volumes of patients undergoing anatomic resection of non-small cell lung carcinoma and to determine the safety and effectiveness of administering enoxaparin for thromboprophylaxis. METHODS:A total of 77 patients were included in the study. A study was conducted on the first group of 42 patients in which enoxaparin prophylaxis (enoxaparin, 40 mg) was subcutaneously injected once a day for a period of three days after the patients underwent anatomic pulmonary resection between March 2016 and March 2018. An enoxaparin-free group was identified and included 35 patients who received no enoxaparin prophylaxis after undergoing anatomic pulmonary resection between February 2013 and February 2016. We compared the changes in hemoglobin (Hb) levels, postoperative 3-day drainage volume, transfusion volume, pulmonary complications and length of stay between the two groups. RESULTS:No differences in postoperative Hb levels, chest drainage volume, transfusion volume, postoperative complications, and length of stay were observed between the two groups. Deep-vein thrombosis was noted in a patient in the enoxaparin-free group. No major bleeding was noted in either group. CONCLUSION:We found that for patients undergoing anatomic resection of primary lung cancer, the blood transfusion and chest drainage volumes did not differ, regardless of whether the patients were given enoxaparin. To the best of our knowledge, the impact of low-molecular-weight heparin on chest tube drainage volume for patients undergoing anatomic resection of non-small cell lung carcinoma has not been investigated before.
METHODS::The aim of the present study was to compare the safety and efficacy of cryoablation (CA) and microwave ablation (MWA) as treatments for non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC treated with CA (n=45) or MWA (n=56) were enrolled in the present study. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS) time and adverse events (AEs). The median PFS times between the two groups were not significantly different (P=0.36): CA, 10 months [95% confidence interval (CI), 7.5-12.4] vs. MWA, 11 months (95% CI, 9.5-12.4). The OS times between the two groups were also not significantly different (P=0.07): CA, 27.5 months (95% CI, 22.8-31.2 months) vs. MWA, 18 months (95% CI, 12.5-23.5). For larger tumors (>3 cm), patients treated with MWA had significantly longer median PFS (P=0.04; MWA, 10.5 months vs. CA, 7.0 months) and OS times (P=0.04; MWA, 24.5 months vs. CA, 14.5 months) compared patients treated with CA. However, for smaller tumors (≤3 cm), median PFS (P=0.79; MWA, 11.0 months vs. CA, 13.0 months) and OS times (P=0.39; MWA, 30.0 months vs. CA, 26.5 months) between the two groups did not differ significantly. The incidence rates of AEs were similar in the two groups (P>0.05). The number of applicators, tumor size and length of the lung traversed by applicators were associated with a higher risk of pneumothorax and intra-pulmonary hemorrhage in the two groups. Treatment with CA resulted in significantly less intraprocedural pain compared with treatment with MWA (P=0.001). Overall, the present study demonstrated that CA and MWA were comparably safe and effective procedures for the treatment of small tumors. However, treatment with MWA was superior compared with CA for the treatment of large tumors.
METHODS:BACKGROUND:BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. PATIENTS AND METHODS:Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS:Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications. CONCLUSION:Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02304809.