scholarly journals Alteredp16INK4and RB1 Expressions Are Associated with Poor Prognosis in Patients with Nonsmall Cell Lung Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Weiqiang Zhao ◽  
Cheng C. Huang ◽  
Gregory A. Otterson ◽  
Marino E. Leon ◽  
Yan Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cells ◽  
Cell Lung Cancer ◽  
Molecular Genetic ◽  
Nonsmall Cell Lung Cancer ◽  
Genetic Alterations ◽  
Adverse Outcomes ◽  
Cell Cycle Regulators ◽  
Functional Inactivation

p16INK4and RB1 are two potent cell cycle regulators to control the G1/S transition by interacting with CDK4/6, E2F, and D-type cyclins, respectively. Depending on the tumour type, genetic alterations resulting in the functional inactivation have frequently been reported in both genes. By contrast, much less is known regarding the overexpression of these proteins in the tumor cells. In this study, expressions of p16INK4RB1, andCDKN2Acopy number variances (CNV) in the tumor cells were assessed by immunohistochemistry and fluorescence in situ hybridization (FISH), respectively, in 73 nonsmall cell lung cancer (NSCLC) with known 5-year survivals. The histologic type (P=0.01), p16INK4(P=0.004), and RB1 (P<0.001) were predictive of survivals. TheCDKN2ACNV (P<0.05) was also significant when compared to those cases without CNV. Therefore, among the molecular genetic prognostic factors, expressions of RB1 and p16INK4in the tumor cells were the most strongly predictive of adverse outcomes in stage I and II nonsquamous NSCLC.

scholarly journals Thymidylate synthase in situ protein expression and survival in stage I nonsmall-cell lung cancer

Cancer ◽  
2008 ◽  
Vol 112 (12) ◽  
pp. 2765-2773 ◽  
Author(s):  
Zhong Zheng ◽  
Xueli Li ◽  
Michael J. Schell ◽  
Tingan Chen ◽  
David Boulware ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Cell Lung Cancer ◽  
Thymidylate Synthase ◽  
Nonsmall Cell Lung Cancer ◽  
Stage I

scholarly journals Detection of Micrometastatic Tumor Cells in pN0 Lymph Nodes of Patients With Completely Resected Nonsmall Cell Lung Cancer

2002 ◽  
Vol 235 (1) ◽  
pp. 133-139 ◽  
Author(s):  
Chun-Dong Gu ◽  
Toshihiro Osaki ◽  
Tsunehiro Oyama ◽  
Masaaki Inoue ◽  
Mantaro Kodate ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lymph Nodes ◽  
Tumor Cells ◽  
Cell Lung Cancer ◽  
Nonsmall Cell Lung Cancer

scholarly journals Gene Characteristics and Prognostic Values of m6A RNA Methylation Regulators in Nonsmall Cell Lung Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Na Li ◽  
Xiaojuan Chen ◽  
Yanhong Liu ◽  
Tieming Zhou ◽  
Wei Li
Keyword(s):  
Lung Cancer ◽  
Mrna Expression ◽  
Cell Lung Cancer ◽  
Copy Number ◽  
Prognostic Significance ◽  
Nonsmall Cell Lung Cancer ◽  
Genetic Alterations ◽  
Regulatory Genes ◽  
Copy Number Loss ◽  
Nsclc Patients

Background. N6-methyladenosine (m6A) is the most common internal modification present in mRNAs and long noncoding RNAs (lncRNAs), associated with tumorigenesis and cancer progression. However, little is known about the roles of m6A and its regulatory genes in nonsmall cell lung cancer (NSCLC). Here, we systematically explored the roles and prognostic significance of m6A-associated regulatory genes in NSCLC. Methods. The copy number variation (CNV), mutation, mRNA expression data, and corresponding clinical pathology information of 1057 NSCLC patients were downloaded from the cancer genome atlas (TCGA) database. The gain and loss levels of CNVs were determined by utilizing segmentation analysis and GISTIC algorithm. The GSEA was conducted to explore the functions related to different levels of m6A regulatory genes. Logrank test was utilized to assess the prognostic significance of m6A-related gene’s CNV. Results. The genetic alterations of ten m6A-associated regulators were identified in 102 independent NSCLC samples and significantly related to advanced tumor stage. Deletions or shallow deletions corresponded to lower mRNA expression while copy number gains or amplifications were related to increased mRNA expression of m6A regulatory genes. Survival analysis showed the patients with copy number loss of FTO with worse disease-free survival (DFS) or overall survival (OS). Besides, copy number loss of YTHDC2 was also with poor OS for NSCLC patients. Moreover, high FTO expression was significantly associated with oxidative phosphorylation, translation, and metabolism of mRNA. Conclusion. Our findings provide novel insight for better understanding of the roles of m6A regulators and RNA epigenetic modification in the pathogenesis of NSCLC.

scholarly journals Generation of Non-Small Cell Lung Cancer Patient-Derived Xenografts to Study Intratumor Heterogeneity

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2446
Author(s):  
Zoi Kanaki ◽  
Alexandra Voutsina ◽  
Athina Markou ◽  
Ioannis S. Pateras ◽  
Konstantinos Potaris ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Cell Lung Cancer ◽  
Genetic Alterations ◽  
Small Cell ◽  
Intratumor Heterogeneity ◽  
Molecular Characteristics ◽  
Tumor Evolution ◽  
Small Cell Lung

Recent advances in sequencing technologies have allowed the in-depth molecular study of tumors, even at the single cell level. Sequencing efforts have uncovered a previously unappreciated heterogeneity among tumor cells, which has been postulated to be the driving force of tumor evolution and to facilitate recurrence, metastasis, and drug resistance. In the current study, focused on early-stage operable non-small cell lung cancer, we used tumor growth in patient-derived xenograft (PDX) models in mice as a fast-forward tumor evolution process to investigate the molecular characteristics of tumor cells that grow in mice, as well as the parameters that affect the grafting efficiency. We found that squamous cell carcinomas grafted significantly more efficiently compared with adenocarcinomas. Advanced stage, patient age and primary tumor size were positively correlated with grafting. Additionally, we isolated and characterized circulating tumor cells (CTC) from patients’ peripheral blood and found that the presence of CTCs expressing epithelial-to-mesenchymal (EMT) markers correlated with the grafting potential. Interestingly, exome sequencing of the PDX tumor identified genetic alterations in DNA repair and genome integrity genes that were under-represented in the human primary counterpart. In conclusion, through the generation of a PDX biobank of NSCLC, we identified the clinical and molecular properties of tumors that affected growth in mice.

Sign in / Sign up

Export Citation Format

Share Document