通过 PDZD2 调控促进肺腺癌发展的 MiR-21-5p 预测
- 作者列表："Cui S","Lou S","Guo W","Jian S","Wu Y","Liu X","Lan X","Jia X
:BACKGROUND Lung adenocarcinoma currently accounts for the highest cancer-related mortality rate worldwide. MiR-21-5p has a vital role in various types of cancers. We have analyzed the miR-21-5p expression level, prognosis, and associated molecular pathways in lung adenocarcinoma with multiple bioinformatics databases. MATERIAL AND METHODS The Cancer Genome Atlas (TCGA) database was employed to fetch the miR-21-5p expression profile in multiple tumors. We used the UALCAN platform to assess the differential regulation of the miR-21-5p in healthy tissue and lung adenocarcinoma. Also, the survival prognosis of the miR-21-5p in each stage of lung adenocarcinoma was done by the Kaplan-Meier database. The STARBASE and UALCAN databases were employed to predict the miR-21-5p target genes, and the levels of target genes and their prognostic value were analyzed. RESULTS MiR-21-5p was overexpressed in the majority of human cancers. MiR-21-5p demonstrated escalated expression in the lung adenocarcinoma tissue in contrast to the normal tissue (P<0.05). Poor prognosis was witnessed in the miR-21-5p high expression group as compared to the low expression group (hazard ratio [HR]= 1.59, P<0.05). PDZD2 was predicted as a miR-21-5p potential target. We found a negative correlation between PDZD2 and miR-21-5p (r=-0.255, P<0.05). PDZD2 was downregulated in lung adenocarcinoma (P<0.05). Overexpression of PDZD2 was associated with a better prognosis of survival in lung adenocarcinoma patients (HR=0.45, P<0.05). CONCLUSIONS MiR-21-5p exhibits the potential to act as a biomarker for the survival prognosis of lung adenocarcinoma. It might be responsible for the onset and progression of lung adenocarcinoma through PDZD2 regulation.
背景: 肺腺癌目前在世界范围内占癌症相关死亡率最高。MiR-21-5p 在各种类型的癌症中起着至关重要的作用。我们利用多个生物信息学数据库分析了肺腺癌 miR-21-5p 表达水平、预后和相关分子通路。材料与方法: 利用癌症基因组图谱 (TCGA) 数据库获取多种肿瘤的 miR-21-5p 表达谱。我们使用 UALCAN 平台评估健康组织和肺腺癌中 miR-21-5p 的差异调节。同时，通过 Kaplan-Meier 数据库对各期肺腺癌 miR-21-5p 的生存预后进行评估。利用 STARBASE 和 UALCAN 数据库预测靶基因 miR-21-5p，分析靶基因水平及其预后价值。结果 MiR-21-5p 在大多数人类癌症中过表达。与正常组织相比，MiR-21-5p 在肺腺癌组织中表达增强 (P<0.05)。与低表达组相比，miR-21-5p 高表达组预后差 (风险比 [HR]= 1.59，P<0.05)。PDZD2 被预测为 miR-21-5p 潜在靶点。我们发现 PDZD2 与 miR-21-5p 呈负相关 (r =-0.255，P<0.05)。PDZD2 在肺腺癌中表达下调 (P<0.05)。PDZD2 过表达与肺腺癌患者较好的生存预后相关 (HR = 0.45，P<0.05)。结论 MiR-21-5p 有可能作为肺腺癌生存预后的生物标志物。它可能通过 PDZD2 调控参与肺腺癌的发生和发展。
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.