ABSTRACT
OBJECTIVE@#To screen the key genes related to the prognosis of lung adenocarcinoma through big data analysis and explore their clinical value and potential mechanism.@*METHODS@#We analyzed GSE18842, GSE27262, and GSE33532 gene expression profile data obtained from the Gene Expression Omnibus (GEO). Bioinformatics methods were used to screen the differentially expressed genes in lung adenocarcinoma tissues and KEGG and GO enrichment analysis was performed, followed by PPI interaction network analysis, module analysis, differential expression analysis, and prognosis analysis. The expressions of MAD2L1 and TTK by immunohistochemistry were verified in 35 non-small cell lung cancer specimens and paired adjacent tissues.@*RESULTS@#We identified a total of 256 genes that showed significant differential expressions in lung adenocarcinoma, including 66 up-regulated and 190 down-regulated genes. Thirty-two up-regulated core genes were screened by functional analysis, and among them 29 were shown to significantly correlate with a poor prognosis of patients with lung adenocarcinoma. All the 29 genes were highly expressed in lung adenocarcinoma tissues compared with normal lung tissues and were mainly enriched in cell cycle pathways. Seven of these key genes were closely related to the spindle assembly checkpoint (SAC) complex and responsible for regulating cell behavior in G2/M phase. We selected SAC-related proteins TTK and MAD2L1 to test their expressions in clinical tumor samples, and detected their overexpression in lung adenocarcinoma tissues as compared with the adjacent tissues.@*CONCLUSIONS@#Seven SAC complex-related genes, including TTK and MAD2L1, are overexpressed in lung adenocarcinoma tissues with close correlation with the prognosis of the patients.
Subject(s)
Humans , Adenocarcinoma of Lung/genetics , Big Data , Cell Cycle Proteins/genetics , Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Lung Neoplasms/genetics , M Phase Cell Cycle Checkpoints , Mad2 Proteins/genetics , Protein Serine-Threonine Kinases/genetics , Protein-Tyrosine Kinases/geneticsABSTRACT
Objective: To investigate the clinical characteristics and diagnosis and treatment process of a patient with invasive mucinous adenocarcinoma (IMAs) of lung, and to improve the clinician's understanding of IMAs. Methods: The general materials, imaging manifestations and treatment plan of a patient with IMAs were collected, and the related literature review was conducted. Results: A 42-year-old female patient was admitted to hospital due to cough and expectoration, the CT examination results showed the bilateral lung patchy shadows∗ the patient was suspected of having pneumonia. After anti-infective treatment, the patient' s symptoms did not improve. The pathological findings of transbronchial lung biopsy (TBLB) and the examination of exfoliated cells of pleural fluid all showed inflammation, and the pathological result of percutaneous biopsy was IMAs. The result of gene detection was 2-point mutation in exon of KRAS. After chemotherapy with paclitaxel plus carboplatin combined with bevacizumab, the symptoms of the patients were improved significantly, and the changes of imaging manifestations were obvious. Conclusion: IMAs is a special pathological type of lung adenocarcinomas (ADCs) with various imaging manifestations and specific gene expression. The treatment principles are different from those of the other types of ADCs.
ABSTRACT
Background and purpose:Gene fusions have been identiifed as recurrent oncogenic events in lung adenocarcinoma. Our purpose are to study the histologic features of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 receptor tyrosine kinase (ROS1) andRETproto-oncogene fusion-positive lung adenocarcinomas and to evaluate the correlation between psammoma bodies and fusion-positive lung adenocarcinomas.Methods:In this study, we performed a comprehensive histologic analysis of 44 fusion-positive (including 15RET, 20ALK and 9ROS1) lung adenocarcinomas and 111 fusion-negative [including 20 epidermal growth factor receptor (EGFR), 20 Kirsten rat sarcoma viral oncogene (K-ras), 71 pan-negative] lung adenocarcinomas.Results:ALK,RET andROS1 fusion-positive lung adenocarcinomas were more prevalent in solid or acinar predominant adenocarcinoma. Multivariate analysis showed that tumors harboring a fusion gene had significantly higher prevalence of the presence of signet ring cells (P=0.000), micropapillary component (P=0.044), mucinous cribriform pattern (P=0.000) and extracellular mucin (P=0.010). The incidence of psammoma bodies was higher in the lung adenocarcinomas with a gene fusion than in tumors without gene fusions (P=0.000). Psammoma bodies were more likely to be found in tumors with any micropapillary component and/or mucinous cribriform pattern than in tumors lacking a micropapillary component and/or mucinous cribriform pattern (P=0.000).Conclusion:Our data showed that the presence of psammoma bodies, micropapillary component, mucinous cribriform pattern, extracellular mucin or signet ring cells may be either sensitive or speciifc to predict tumors harboring a fusion gene. These distinct morphologic features may be helpful in selecting cases for further accurate molecular testing.