Humans ; Lung Neoplasms ; metabolism ; Receptor for Advanced Glycation End Products ; metabolism

OBJECTIVETo study the expression of hTERT mRNA and Mad1 protein in lung cancer of Gejiu and Xuanwei and normal lung tissue and to investigate their correlations with lung cancer.

METHODSMad1 protein was detected by immunohistochemistry S-P method, and hTERT message RNA (mRNA) was detected by in situ hybridization (ISH) in 40 specimens of lung cancer of Gejiu Tin miners and 20 specimens of lung cancer of Xuanwei peasants and 20 specimens of normal lung tissue. The positive signals were quantitatively analyzed by HPIAS-100.

RESULTSThe positive unit (PU) of Mad1 protein was 16.77 +/- 6.01 in Gejiu Tin Miners lung cancer group, and 19.36 +/- 4.54 in Xuanwei peasant lung cancer group, compared with the normal lung tissue (46.05 +/- 7.26). The difference was highly significant (P < 0.01); The PU of hTERT mRNA was 72.10 +/- 13.07 in Gejiu Tin miners lung cancer group, and 74.20 +/- 15.17 in Xuanwei peasant lung cancer group, which was higher than that in normal tissue group (10.70 +/- 2.21). The difference was significant (P < 0.01). The expression of Mad1 protein was negatively correlated with the expression hTERT mRNA (P < 0.05, r = 0.9881, r = -0.999).

CONCLUSIONReduced hTERT mRNA expression may play an important role in the occurrence of lung cancer. The expression of hTERT mRNA and deletion of Mad1 protein are closely related to pathogenesis of lung cancer.

Cell Cycle Proteins ; metabolism ; China ; Female ; Humans ; Lung ; metabolism ; Lung Neoplasms ; metabolism ; Male ; Mining ; Nuclear Proteins ; metabolism ; Telomerase ; metabolism

Lung cancer is the leading cause of cancer-related deaths worldwide. Targeted therapy is beneficial in most cases, but the development of drug resistance stands as an obstacle to good prognosis. Multiple mechanisms were explored such as genetic alterations, activation of bypass signaling, and phenotypic transition. These intrinsic and/or extrinsic dynamic regulations facilitate tumor cell survival in meeting the demands of signaling under different stimulus. This review introduces lung cancer plasticity and heterogeneity and their correlation with drug resistance. While cancer plasticity and heterogeneity play an essential role in the development of drug resistance, the manipulation of them may bring some inspirations to cancer prognosis and treatment. That is to say, lung cancer plasticity and heterogeneity present us with not only challenges but also opportunities.
Carcinoma, Non-Small-Cell Lung ; genetics ; metabolism ; Drug Resistance, Neoplasm ; genetics ; Humans ; Lung Neoplasms ; genetics ; metabolism

Objective Many studies have revealed the crucial roles of miRNA in multiple human cancers, including lung adenocarcinoma (LUAD). In this study, we sought to explore new miRNA-mRNA pairs that are associated with LUAD prognosis. Methods A novel miRNA-mRNA regulatory network associated with prognosis in LUAD was identified and validated using the bioinformatic tools including OncomiR database, StarBase, miRnet, GEPIA2, UALCAN. Results Twenty key miRNAs were compiled after the analysis of the expression and prognostic value in OncomiR and StarBase. Targeted mRNAs of these key miRNAs were predicted in miRnet, and the resulting mRNAs were also analyzed for their prognostic values and expression patterns in GEPIA2 and UALCAN, respectively. Further expression correlation analysis was performed in StarBase. Subsequently, a new miRNA-mRNA network was built, of which each RNA pair showed negative expression correlation, opposite expression pattern, and prognostic value. Protein-protein interaction network was under construction for the mRNAs, and 19 hub genes were determined. Enrichment analysis showed that "Cell Cycle, Mitotic" was the most significantly enriched term. Then, a miRNA-hub gene sub-network was built. We selected and validated the regulatory relationship of some miRNA-hub pairs, including hsa-miR-1976/RFC2, hsa-let-7c-5p/RFC2, hsa-let-7c-5p/ESPL1, hsa-let-7c-5p/CDC25A, and hsa-miR-101-3p/KIF2C. Moreover, over-expression of hsa-miR-1976 and hsa-let-7c-5p resulted in significant cell cycle arrest. Conclusions Our results determined new prognosis-associated miRNA-mRNA pairs and might shed further light on the mechanism via which miRNA-mRNA network influences prognosis in LUAD.
Adenocarcinoma of Lung/genetics* ; Humans ; Lung Neoplasms/pathology* ; MicroRNAs/metabolism* ; Prognosis ; RNA, Messenger/metabolism*

OBJECTIVE: To explore the expression of fibronectin type Ⅲ domain containing 1(FNDC1) protein in lung adenocarcinoma and its prognostic significance. METHODS: The expression of FNDC1 in lung adenocarcinoma was predicted by analysis of data from GEO database and GEPIA, and the results were verified by immunohistochemical staining in 92 pairs of clinical specimens of lung adenocarcinoma and adjacent tissues.We further analyzed the correlation of FNDC1 expression with the clinicopathological features of the patients, and evaluated its prognostic value using Cox survival analysis. RESULTS: Analysis of the data form GEO database and GEPIA showed a significantly higher expression level of FNDC1 in lung adenocarcinoma than in matched normal tissues (P < 0.05).Kaplan-Meier survival analysis suggested that a high expression of FNDC1 protein was associated with a significantly shorter overall survival time of the patients (P < 0.05).Immunohistochemistry of the clinical specimens also showed a significantly higher protein expression of FNDC1 in lung adenocarcinoma tissues than in paired adjacent tissues (P < 0.001).A high expression of FNDC1 protein was significantly correlated with advanced clinical stage, T stage and N stage (P < 0.05).Cox univariate and multivariate regression survival analysis indicated that an increased expression of FNDC1 was an independent risk factor for poor prognosis of the patients with lung adenocarcinoma (P < 0.05). CONCLUSION FNDC1 protein is highly expressed in patients with lung adenocarcinoma and in closely related with the occurrence, progression and prognosis of the tumor, suggesting the value of FNDC1 protein as a potential biomarker for assessment of the survival and prognosis of patients with lung adenocarcinoma.
Adenocarcinoma of Lung/metabolism* ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms/metabolism* ; Neoplasm Proteins/genetics* ; Prognosis ; Proteins

OBJECTIVETo identify differentially expressed microRNAs (miRNAs) related to lung adenocarcinoma in Xuanwei region and predict their target genes and related signaling pathways based on bioinformatic analysis.

METHODSHigh-throughput microarray assay was performed to detect miRNA expression profiles in 34 paired human lung adenocarcinoma and adjacent normal tissues (including 24 cases in Xuanwei region and 10 in other regions). Gene ontology and KEGG pathway analyses were used to predict the target genes and the regulatory signaling pathways.

RESULTSThirty-four miRNAs were differentially expressed in lung adenocarcinoma tissues in cases in Xuanwei region as compared with cases in other regions, including 23 upregulated and 11 downregulated miRNAs. The predicted target genes included GF, RTK, SOS, IRS1, BCAP, CYTOKINSR, ECM, ITGB, FAK and Gbeta;Y involving the PI3K/Alt, WNT and MAPK pathways.

CONCLUSIONThe specific microRNA expression profiles of lung adenocarcinoma in cases found in Xuanwei region allow for a better understanding of the pathogenesis of lung adenocarcinoma in Xuanwei. The predicted target genes may involve the PI3K/Alt, WNT and MAPK pathways.

Adenocarcinoma ; genetics ; metabolism ; Computational Biology ; Gene Expression Profiling ; Humans ; Lung ; metabolism ; Lung Neoplasms ; genetics ; metabolism ; MicroRNAs ; genetics ; metabolism ; Signal Transduction

OBJECTIVE: To observe the expression profile of heat shock proteins (HSPs) including HSP70, inducible HSP90 (HSP86) and aB-crystallin in cells and tissues of lung adenocarcinoma. METHODS: Western blotting and reverse transcriptional-polymerase chain reaction (RT-PCR) were performed to detect the expression of HSP70, HSP86 and aB-crystallin both in the protein and mRNA level respectively. RESULTS: Compared with normal lung tissue and human bronchial epithelium (HBE) cells, RT-PCR and Western blotting showed that the expression of HSP70, HSP86 and alphaB crystallin increased significantly in both the mRNA and protein level in the cancer tissue and A549 human lung adenocarcinoma cells. Among the 3 sub-families of HSPs, the expression of HSP70 mRNA and protein increased most in both the lung tissue of cancer and A549 human adenocarcinoma cell lines. CONCLUSION The expression of HSPs is higher in the lung adenocarcinoma and A549 cells than that in the normal lung tissues and HBE cells. Among the HSP family, HSP70 is the most up-regulated member in the tissue and cells of lung adenocarcinoma.
Adenocarcinoma ; metabolism ; Adenocarcinoma of Lung ; Cells, Cultured ; Epithelial Cells ; cytology ; metabolism ; Heat-Shock Proteins ; metabolism ; Humans ; Lung ; cytology ; metabolism ; Lung Neoplasms ; metabolism ; Tumor Cells, Cultured

Radiation therapy is one of the main treatment methods for patients with thoracic malignant tumors, which can effectively improve the survival rate of the patients. However, radiation therapy can also cause damage to normal tissues while treating tumors, leading to radiation-induced lung injury such as radiation pneumonia and pulmonary fibrosis. Radiation-induced lung injury is a complex pathophysiological process involving many factors, and its prevention and treatment is one of the difficult problems in the field of radiation medicine. Therefore, the search for sensitive predictors of radiation-induced lung injury can guide clinical radiotherapy and reduce the incidence of radiation-induced lung injury. With the in-depth study of intestinal flora, it can drive immune cells or metabolites to reach lung tissue through the circulatory system to play a role, and participate in the occurrence, development and treatment of lung diseases. At present, there are few studies on intestinal flora and radiation-induced lung injury. Therefore, this paper will comprehensively elaborate the interaction between intestinal flora and radiation-induced lung injury, so as to provide a new direction and strategy for studying the protective effect of intestinal flora on radiation-induced lung injury.
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Humans ; Lung Injury/prevention & control* ; Gastrointestinal Microbiome ; Lung Neoplasms/radiotherapy* ; Lung/pathology* ; Radiation Injuries/metabolism* ; Thoracic Neoplasms

Animals ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Neoplastic Stem Cells ; pathology

HLA Antigens ; immunology ; metabolism ; Humans ; Lung Neoplasms ; immunology