scholarly journals RNA-sequencing analysis identifies downstream genes of TCF4 involved in the development of non-small cell lung cancer.

IBJ Plus ◽  
2018 ◽  
Author(s):  
◽  
◽  
Olga Vera ◽  
Alvaro García Guede ◽  
Carlos Rodríguez Antolín ◽  
...  
2005 ◽  
Vol 23 (1) ◽  
pp. 154-164 ◽  
Author(s):  
Yu-Chien Wang ◽  
Ruo-Kai Lin ◽  
Yi-Hung Tan ◽  
Jung-Ta Chen ◽  
Chih-Yi Chen ◽  
...  

Purpose We found a relatively reduced frequency of p53 mutation with a much greater frequency of p53 protein overexpression, which reflected stabilization of p53 protein in the absence of p53 gene mutation. Therefore, we investigated the possibility of alternative mechanisms leading to p53 protein stabilization. Patients and Methods We performed gene and protein alteration studies on p53 and its upstream effectors, MDM2 and p14ARF, in tumors from 94 non–small-cell lung cancer (NSCLC) patients. Results Immunohistochemical and sequencing analyses indicated that 37 tumors showed overexpression of wild-type p53. An absence of nuclear staining of MDM2 protein was found in 95% of these tumors (35 of 37; P < .001). The tumors with negative MDM2 staining showed a significantly high concordance of loss of Akt activity and low MDM2 mRNA expression (P < .001). Sequencing analysis revealed five distinct MDM2 splicing variants disrupting the conserved p53 binding domain. Corresponding variant proteins were detected in three lung cancer cell lines using the Western blot analysis. Our results also indicated that among the tumors with overexpression of the wild-type p53, 92% (34 of 37) showed immunoreactivity to p14ARF (P = .001). In addition, the deregulation of p53 and MDM2 genes was significantly associated with squamous lung cancer (P < .05) and was correlated with advanced stages (P < .05) and poor prognosis (P < .05). Conclusion Our data suggest that immunopositivity of p14ARF together with a low expression of MDM2 contributes to accumulation of the wild-type p53, and that deregulation of the p53-MDM2-p14ARF pathway is important in the pathogenesis and outcome of a subset of NSCLC.


Lung Cancer ◽  
2014 ◽  
Vol 84 (3) ◽  
pp. 229-235 ◽  
Author(s):  
Seon-Sook Han ◽  
Woo Jin Kim ◽  
Yoonki Hong ◽  
Seok-Ho Hong ◽  
Seung-Joon Lee ◽  
...  

Author(s):  
Neelambika B Hiremath ◽  
Dayananda P

Background and Objective: The advent of Next Generation Sequencing (NGS) has created a high throughput platform, to identify disease traits and phenotypic characteristics using RNASeq Sequencing analysis in humans. Non-small cell lung cancer (NSCLC), a lethal disease accounts for 85 percent of most lung cancers with very small window ofsurvival rate. The decision of tumour image bio marker impression can be improved by gene profile. Hence there is a need to characterise the variants in the disease manifestation. Methods: To understand the SNP’s in the major genes responsible for NSCLC, RNASeq data of patients aged above 50 years, were downloaded from SRA database. The quality matrix analysis is mapped to Genome reference consortium human build 38 (GRCh38) to call the variants and identify SNP’s with the tuxedo protocol. Results: The SNP’s and the patterns of variants were analysed to see the comparison between healthy individual and NSCLC patients, and in between patients of different age. Oncogenes commonly associated with the NSCLC like KRAS, EGFR, ALK, BRAF and HER2 were mainly analysed to see the SNP’s and their characterisations with respect to the functional change was done. Conclusion: The SNP’s with the greater quality scores belonging to the above said genes were identified which gives us a baseline to understand the NSCLC at the Genomic level. Further fold change of these genes to the frequency of variant can be mapped to understand the NSCLC at a greater depth.


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