Aberrant Signaling Pathways in Squamous Cell Lung Carcinoma

Overview

Journal Cancer Inform

Publisher Sage Publications

Specialty Biomedical Engineering

Date 2011 Dec 17

PMID 22174565

Citations 26

Authors

Ivy Shi

Nooshin Hashemi Sadraei

Zhong-Hui Duan

Ting Shi

Affiliations

Soon will be listed here.

Abstract

Lung cancer is the second most commonly occurring non-cutaneous cancer in the United States with the highest mortality rate among both men and women. In this study, we utilized three lung cancer microarray datasets generated by previous researchers to identify differentially expressed genes, altered signaling pathways, and assess the involvement of Hedgehog (Hh) pathway. The three datasets contain the expression levels of tens of thousands genes in normal lung tissues and squamous cell lung carcinoma. The datasets were combined and analyzed. The dysregulated genes and altered signaling pathways were identified using statistical methods. We then performed Fisher's exact test on the significance of the association of Hh pathway downstream genes and squamous cell lung carcinoma.395 genes were found commonly differentially expressed in squamous cell lung carcinoma. The genes encoding fibrous structural protein keratins and cell cycle dependent genes encoding cyclin-dependent kinases were significantly up-regulated while the ones encoding LIM domains were down. Over 100 signaling pathways were implicated in squamous cell lung carcinoma, including cell cycle regulation pathway, p53 tumor-suppressor pathway, IL-8 signaling, Wnt-β-catenin pathway, mTOR signaling and EGF signaling. In addition, 37 out of 223 downstream molecules of Hh pathway were altered. The P-value from the Fisher's exact test indicates that Hh signaling is implicated in squamous cell lung carcinoma.Numerous genes were altered and multiple pathways were dysfunctional in squamous cell lung carcinoma. Many of the altered genes have been implicated in different types of carcinoma while some are organ-specific. Hh signaling is implicated in squamous cell lung cancer, opening the door for exploring new cancer therapeutic treatment using GLI antagonist GANT 61.

Citing Articles

Uncovering hub genes and immunological characteristics for heart failure utilizing RRA, WGCNA and Machine learning.

Tu D, Xu Q, Zuo X, Ma C Int J Cardiol Heart Vasc. 2024; 51:101335.

PMID: 38371312 PMC: 10869931. DOI: 10.1016/j.ijcha.2024.101335.

Identification of Potential Prognostic Biomarkers Associated with Monocyte Infiltration in Lung Squamous Cell Carcinoma.

Liu H, Yan B, Chen Y, Pang J, Li Y, Zhang Z Biomed Res Int. 2022; 2022:6860510.

PMID: 35993054 PMC: 9388304. DOI: 10.1155/2022/6860510.

Xprediction: Explainable EGFR-TKIs response prediction based on drug sensitivity specific gene networks.

Park H, Yamaguchi R, Imoto S, Miyano S PLoS One. 2022; 17(5):e0261630.

PMID: 35584089 PMC: 9116684. DOI: 10.1371/journal.pone.0261630.

Infection by High-Risk Human Papillomaviruses, Epithelial-to-Mesenchymal Transition and Squamous Pre-Malignant or Malignant Lesions of the Uterine Cervix: A Series of Chained Events?.

Barillari G, Bei R, Manzari V, Modesti A Int J Mol Sci. 2021; 22(24).

PMID: 34948338 PMC: 8703928. DOI: 10.3390/ijms222413543.

Low KRT15 expression is associated with poor prognosis in patients with breast invasive carcinoma.

Zhong P, Shu R, Wu H, Liu Z, Shen X, Hu Y Exp Ther Med. 2021; 21(4):305.

PMID: 33717248 PMC: 7885068. DOI: 10.3892/etm.2021.9736.

References

Shepherd F, Pereira J, Ciuleanu T, Tan E, Hirsh V, Thongprasert S . Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005; 353(2):123-32. DOI: 10.1056/NEJMoa050753. View

Villares G, Zigler M, Dobroff A, Wang H, Song R, Melnikova V . Protease activated receptor-1 inhibits the Maspin tumor-suppressor gene to determine the melanoma metastatic phenotype. Proc Natl Acad Sci U S A. 2010; 108(2):626-31. PMC: 3021062. DOI: 10.1073/pnas.1006886108. View

Takeuchi K, Ito F . EGF receptor in relation to tumor development: molecular basis of responsiveness of cancer cells to EGFR-targeting tyrosine kinase inhibitors. FEBS J. 2009; 277(2):316-26. DOI: 10.1111/j.1742-4658.2009.07450.x. View

Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H . Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010; 362(25):2380-8. DOI: 10.1056/NEJMoa0909530. View

Massion P, Carbone D . The molecular basis of lung cancer: molecular abnormalities and therapeutic implications. Respir Res. 2003; 4:12. PMC: 314397. DOI: 10.1186/1465-9921-4-12. View

Derisi J, Penland L, Brown P, Bittner M, Meltzer P, Ray M . Use of a cDNA microarray to analyse gene expression patterns in human cancer. Nat Genet. 1996; 14(4):457-60. DOI: 10.1038/ng1296-457. View

Aleem E, Kiyokawa H, Kaldis P . Cdc2-cyclin E complexes regulate the G1/S phase transition. Nat Cell Biol. 2005; 7(8):831-6. DOI: 10.1038/ncb1284. View

Schweizer J, Bowden P, Coulombe P, Langbein L, Lane E, Magin T . New consensus nomenclature for mammalian keratins. J Cell Biol. 2006; 174(2):169-74. PMC: 2064177. DOI: 10.1083/jcb.200603161. View

Motzer R, Escudier B, Oudard S, Hutson T, Porta C, Bracarda S . Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008; 372(9637):449-56. DOI: 10.1016/S0140-6736(08)61039-9. View

10.

Wu J, Wu S, Yang C, Gow C, Chang Y, Yu C . Lung cancer with epidermal growth factor receptor exon 20 mutations is associated with poor gefitinib treatment response. Clin Cancer Res. 2008; 14(15):4877-82. DOI: 10.1158/1078-0432.CCR-07-5123. View

11.

Bhattacharjee A, Richards W, Staunton J, Li C, Monti S, Vasa P . Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc Natl Acad Sci U S A. 2001; 98(24):13790-5. PMC: 61120. DOI: 10.1073/pnas.191502998. View

12.

Maass N, Hojo T, Ueding M, Luttges J, Kloppel G, Jonat W . Expression of the tumor suppressor gene Maspin in human pancreatic cancers. Clin Cancer Res. 2001; 7(4):812-7. View

13.

Reguart N, Cardona A, Rosell R . Role of erlotinib in first-line and maintenance treatment of advanced non-small-cell lung cancer. Cancer Manag Res. 2010; 2:143-56. PMC: 3004579. DOI: 10.2147/cmar.s5398. View

14.

Sandler A, Gray R, Perry M, Brahmer J, Schiller J, Dowlati A . Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006; 355(24):2542-50. DOI: 10.1056/NEJMoa061884. View

15.

Abraham S, Zhang W, Greenberg N, Zhang M . Maspin functions as tumor suppressor by increasing cell adhesion to extracellular matrix in prostate tumor cells. J Urol. 2003; 169(3):1157-61. DOI: 10.1097/01.ju.0000040245.70349.37. View

16.

Taipale J, Beachy P . The Hedgehog and Wnt signalling pathways in cancer. Nature. 2001; 411(6835):349-54. DOI: 10.1038/35077219. View

17.

Sanchez P, Hernandez A, Stecca B, Kahler A, DeGueme A, Barrett A . Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. Proc Natl Acad Sci U S A. 2004; 101(34):12561-6. PMC: 514658. DOI: 10.1073/pnas.0404956101. View

18.

Au N, Gown A, Cheang M, Huntsman D, Yorida E, Elliott W . P63 expression in lung carcinoma: a tissue microarray study of 408 cases. Appl Immunohistochem Mol Morphol. 2004; 12(3):240-7. DOI: 10.1097/00129039-200409000-00010. View

19.

Lauth M, Bergstrom A, Shimokawa T, Toftgard R . Inhibition of GLI-mediated transcription and tumor cell growth by small-molecule antagonists. Proc Natl Acad Sci U S A. 2007; 104(20):8455-60. PMC: 1866313. DOI: 10.1073/pnas.0609699104. View

20.

Kim Y, Girard L, Giacomini C, Wang P, Hernandez-Boussard T, Tibshirani R . Combined microarray analysis of small cell lung cancer reveals altered apoptotic balance and distinct expression signatures of MYC family gene amplification. Oncogene. 2005; 25(1):130-8. DOI: 10.1038/sj.onc.1208997. View