ABSTRACT
Background: In the past, multiple studies have offered incremental evidence that indicates that competitive endogenous RNA (ceRNA) regulatory networks are involved in tumor growth and present novel therapeutic targets. Herein, we investigated the impact of thymidine kinase 1 (TK1)-related ceRNA networks on the prognosis of non-small cell lung cancer (NSCLC). Methods: TK1 expression data in NSCLC and normal tissue samples were retrieved from the Cancer Genome Atlas (TCGA) database and were then compared. Thereafter, the findings of the immunohistochemical staining experiments and clinical follow-up data derived from patients with NSCLC were used for conducting prognostic analysis. The starBase database was searched to determine TK1-targeted microRNAs and long non-coding RNAs, and clinical data from TCGA were used for survival analysis to construct a ceRNA network associated with TK1 expression and prognosis. Finally, the roles played by methylation and immunity in the prognosis and treatment of NSCLC were analyzed. Results: Our findings revealed that the cancer tissues expressed significantly higher TK1 levels than normal tissues, and the follow-up clinical data revealed that the prognosis was generally worse in the high-expression patients than in the low-expression patients. In addition, clinical data collected from the starBase and TCGA databases showed that the LINC00665/has-let-7b-5p/TK1 network could influence the growth and prognosis of NSCLC. It was also noted that the TK1 methylation site was correlated with the prognosis of NSCLC, and immunoprognostic analysis further indicated that patients with higher TK1 expression levels displayed a worse prognosis. Conclusion: When the regulatory network of LINC00665/has-let-7b-5p/TK1 was assessed, it was observed that elevated TK1 levels may affect the prognosis of NSCLC. Therefore, it could be considered a prognostic biomarker and a probable therapeutic target for predicting NSCLC prognosis.
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BACKGROUND: Although pleurodesis is usually used to reduce the recurrence rate for primary spontaneous pneumothorax (PSP) in surgery, existing techniques cannot meet the higher requirements of little surgical injury and less relapse. Hence, we developed a new pleurodesis technique and named multipoint pleura cautery. AIM: In this study, we aimed to investigate the effectiveness and outcomes of the uniportal video-assisted thoracoscopic surgery C-shaped pleura cautery in the surgical treatment of PSP. To the best of our knowledge, this is a new surgical technique for pleurodesis and must be of concern. PATIENTS AND METHODS: The medical records of 20 patients undergoing surgery for C-shaped pleura cautery between 2015 and 2017 were reviewed. The patients were evaluated with regard to age, gender, body mass index, smoking habit, operation time, duration of hospitalization, post-operative pain and follow-up. RESULTS: We have performed a bullectomy combined C-shaped pleura cautery for 20 patients with PSP from January 2016 to December 2017. None of the patients suffered post-operative bleeding and haematothorax complications, and one was ipsilateral relapsed 5 months after surgery. The lung computed tomography showed that recurrence of pneumothorax was due to air leakage in the right lower lung, and there was no air leakage at the site where pleurodesis had been performed. CONCLUSIONS: Although this technique requires further investigation, it may be a useful method of pleurodesis.
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BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common malignant tumor in China. miR-486 was found to be associated with many tumors. In previous study, we aimed to investigate the expression and prognostic value of miR-486 in patients with NSCLC. METHODS: In order to measure the expression of miR-486 in 140 NSCLC patients, in situ hybridization (ISH) was made. The staining of miR-486 was scored by two independent investigators. Then, the prognostic value of miR-486 was evaluated by plotting Kaplan-Meier survival curves and making multivariate analysis. RESULTS: miR-486 was mainly expressed in the cytoplasm of tumor cells. miR-486 expression was corrected with tumor differentiation (P=0.011) but not with any other clinicopathological characteristics. However, high expression of miR-486 was significantly correlated with shortened overall survival (OS) in NSCLC patients (P=0.001), especially in stage I patients (P=0.005). Multivariate analysis revealed that miR-486 was an independent prognostic factor in NSCLC patients (P=0.002). CONCLUSIONS: miR-486 high expression predicts poor survival in patients with NSCLC. miR-486 could be used as an unfavorable prognostic biomarker for NSCLC patients.
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PURPOSE: Lung cancer, the leading cause of cancer-related death worldwide, shows a poor 5-year overall survival rate. In our previous study, we demonstrated that miR-486-5p can be a potential blood-based biomarker for early diagnosis and recurrence prediction of non-small cell lung cancer (NSCLC). The aim of the present study was to investigate the possible roles and related target genes of miR-486-5p in NSCLC progression. METHODS: pcDNA3.1(+)/Pri-miR486 recombinant plasmid and miR-486-5p inhibitor were transfected into NSCLC cells and theirs effects were evaluated by qRT-PCR. Then, MTT assay and Colony formation assay were performed to determine the potential roles of miR-486-5p played on NSCLC cellular proliferation and cloning in vitro. We also initially investigated the target genes of miR-486-5p by using bioinformatic methods, qRT-PCR and western blot. RESULTS: pcDNA3.1(+)/Pri-miR486 recombinant plasmid significantly upregulated the expression of miR-486-5p, while miR-486-5p inhibitor significantly downregulated its expression. Upregulation of miR-486-5p promoted the cellular proliferation and cloning, while miR-486-5p silencing restrained the cellular proliferation and cloning. Furthermore, four potential target genes (PIK3R1, PTEN, MAP3K7 and FOXO1) of miR-486-5p were screened out. Finally, we found that upregulation of miR-486-5p in NSCLC cells significantly reduced PTEN and increased AKT expression levels, whereas miR-486-5p silencing increased PTEN and reduced AKT expression. Therefore, we believe that miR-486-5p can regulate PTEN-PI3 K/AKT signaling. CONCLUSIONS: miR-486-5p acts as an oncogene in the progression of NSCLC by influencing PTEN-PI3 K/AKT signaling. miR-486-5p may provide potential therapeutic targets for NSCLC.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Cell Movement/genetics , Lung Neoplasms/genetics , MicroRNAs/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Down-Regulation , Humans , Neoplasm Recurrence, Local/genetics , PTEN Phosphohydrolase/metabolismABSTRACT
BACKGROUND Cisplatin (DDP)-based systemic chemotherapy has been widely used in the treatment of postoperative or advanced NSCLC patients, however, its effective rate is only 14~40%. HIF-2α can upregulate drug-resistant-related genes expression and lead to chemotherapy resistance in many tumors. However, little is known about the relationship between HIF-2α and chemotherapy resistance of lung cancer cells. MATERIAL AND METHODS In our study, the siRNA expression vectors targeting the HIF-2α gene were designed, constructed, and transfected into A549 cells. MTT assay and western blot analysis of P-glycoprotein 1 (P-gp) were used to explore the transfer influence of HIF-2α gene silencing on the A549 cells in the cisplatin-based chemotherapy resistance. RESULTS After transfection with the siRNAHIF-2α into A549 cells, mRNA and protein expression of HIF-2α were downregulated. At the same time, expression of P-gp decreased significantly. Furthermore, the sensitivity to cisplatin significantly increased. CONCLUSIONS The constructed siRNA expression vectors can effectively suppress the expression of HIF-2α and P-gp, which then can reverse the chemotherapy resistance of A549 cells.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/metabolism , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , A549 Cells , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Basic Helix-Loop-Helix Transcription Factors/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Cisplatin/pharmacology , Down-Regulation , Drug Resistance, Neoplasm , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , RNA, Messenger/metabolism , RNA, Small Interfering/geneticsABSTRACT
PURPOSE: To investigate the expression profile and prognostic value of SLC6A10P in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: TCGA datasets were used to investigate the differential expression of SLC6A10P in NSCLC, lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC). Expression of SLC6A10P was measured by in situ hybridization in tissue microarrays containing 136 NSCLC (51 LUAD and 85 LUSC) patients. The prognostic value of SLC6A10P was then evaluated. RESULTS: SLC6A10P was highly expressed in tumor tissues compared with normal lung tissues. High SLC6A10P expression was associated with lymph node metastasis (NSCLC, P = 0.0054; LUAD, P = 0.0149), more advanced tumor stage (NSCLC, P = 0.0126; LUAD, P = 0.0416) and poor overall survival (NSCLC, P = 0.0248; LUAD, P = 0.0316) in NSCLC and LUAD. Multivariate analysis revealed that SLC6A10P was an independent prognostic factor in LUAD patients (P = 0.017). SLC6A10P showed no association with clinicopathological parameters and no prognostic value in LUSC. CONCLUSION: SLC6A10P is highly expressed in tumor tissues and its high expression predictspoor survival in patients with LUAD. SLC6A10P might serve as a novel therapeutic target and prognostic biomarker in LUAD patients in the future.
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HIF-α may play an important role in the process of tumorigenesis as well as tumor progression. Although a number of investigations have established the significance of HIF-1α in several human tumors, there is still little information available on the clinical significance of HIF-2α expression in non-small cell lung cancer (NSCLC). In present study, immunohistologic expression of HIF-1α/ HIF-2α was studied in a tissue microarray of 140 Stage I-III NSCLCs and correlated with clinicopathologic parameters and clinical outcome. We found that HIF-1α/ HIF-2α showed a cytoplasmic pattern of expression in tumor cells while normal lung components showed negative or weak cytoplasmic staining. High HIF-1α and HIF-2α expression was noted in 49/140 (35.0%) and in 64/140 (45.7%) of the cases respectively. There was no direct correlation between HIF-1α and HIF-2α expression ( p = 0.200). The high HIF-2α expression was associated with histology (squamous cell carcinoma vs. adenocarcinomas) in these patients ( p = 0.001). Patients in advanced tumor stage had frequent high expression of HIF-2α ( p = 0.007), and the similar high expression was also observed in advanced T or N stage ( p = 0.030 and 0.043, respectively). HIF-1α showed a marginal association with T stage ( p = 0.084), which showed a higher expression in early tumor stage. Univariate analysis of the overall survival demonstrates that HIF-2α expression but not HIF-1α was related to poor outcome ( p = 0.005) and it retained significance in multivariate analysis ( p = 0.046). In conclusion, HIF-2α expression was related to tumor size, lymph node metastasis, tumor stage and histology. We also found a positive prognostic value of HIF-2α protein expression. HIF-2α might serve as a potential prognosis biomarker in evaluating progression and prognosis of NSCLC. We believe that our study will be of great benefit to the clinical treatment and prognostic evaluation of NSCLC.