Upregulated Expression of the Growth Arrest-Specific-2 (GAS2) Gene in Colorectal Cancer, and its Relation to Cancer Progression and Prognosis

Document Type : Original Article (s)


1 Department of Clinical Biochemistry, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran

2 Assistant Professor, Department of Molecular Medicine and Genetics, School of Medicine, Ilam University of Medical Sciences, Ilam, Iran

3 Associate Professor, Department of Clinical Biochemistry, School of Medicine AND Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran


Background: Growth arrest-specific 2 (GAS2) gene is implicated in a variety of cellular functions such as cell cycle, apoptosis, and proliferation, and may be potentially involved in cancer progression. However, whether GAS2 is associated with colorectal cancer (CRC) progression and prognosis remains to be uncovered. Thus, this study investigated the association of GAS2 expression in tumor with CRC progression and prognosis.Methods: In the case-control study, surgical tumor and adjacent normal tissues from 40 patients with CRC were collected at Cancer Institute of Imam Khomeini Hospital in Tehran, Iran, and relative expression level of GAS2 in the tissues was assayed using quantitative real-time polymerase chain reaction method. The correlation of tumor GAS2 expression with the clinicopathological features and overall survival rate of patients was determined.Findings: The relative expression level of GAS2 in tumor tissues was significantly elevated compared to the adjacent normal tissues [1.96 (1.17-3.40) vs. 1.10 (1.00-1.31), P < 0.001]. Moreover, the expression levels of GAS2 in tumor tissues were significantly associated with clinicopathological features of cancer including tumor stage in Tumor spread, Lymph node spread, and Metastasis (TNM) staging (P = 0.010), grade (P = 0.010), size (P = 0.030), and lymphatic (P = 0.030) and vascular invasion (P = 0.040) as well as the decreased overall survival (P = 0.040).Conclusion: Elevated expression of GAS2 in CRC is associated with cancer progression indices and poor prognosis; hence it may be served as a prognostic biomarker in CRC.


  1. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017; 66(4): 683-91.
  2. Liu X, Bi Y, Wang H, Meng R, Zhou W, Zhang G, et al. Different trends in colorectal cancer mortality between age groups in China: An age-period-cohort and joinpoint analysis. Public Health 2019; 166: 45-52.
  3. Saini MK, Sanyal SN. Cell cycle regulation and apoptotic cell death in experimental colon carcinogenesis: Intervening with cyclooxygenase-2 inhibitors. Nutr Cancer 2015; 67(4): 620-36.
  4. Brancolini C, Bottega S, Schneider C. Gas2, a growth arrest-specific protein, is a component of the microfilament network system. J Cell Biol 1992; 117(6): 1251-61.
  5. Brancolini C, Schneider C. Phosphorylation of the growth arrest-specific protein Gas2 is coupled to actin rearrangements during Go-->G1 transition in NIH 3T3 cells. J Cell Biol 1994; 124(5): 743-56.
  6. Benetti R, Del Sal G, Monte M, Paroni G, Brancolini C, Schneider C. The death substrate Gas2 binds m-calpain and increases susceptibility to p53-dependent apoptosis. EMBO J 2001; 20(11): 2702-14.
  7. Brancolini C, Marzinotto S, Schneider C. Susceptibility to p53 dependent apoptosis correlates with increased levels of Gas2 and Gas3 proteins. Cell Death Differ 1997; 4(3): 247-53.
  8. Zhang CL, Liu X, He QJ, Zheng H, Xu S, Xiong XD, et al. miR3425p promotes Zmpste24deficient mouse embryonic fibroblasts proliferation by suppressing GAS2. Mol Med Rep 2017; 16(6): 8944-52.
  9. Sun L, Zhou H, Liu H, Ge Y, Zhang X, Ma W, et al. GAS2-Calpain2 axis contributes to the growth of leukemic cells. Acta Biochim Biophys Sin (Shanghai) 2015; 47(10): 795-804.
  10. Benetti R, Copetti T, Dell'Orso S, Melloni E, Brancolini C, Monte M, et al. The calpain system is involved in the constitutive regulation of beta-catenin signaling functions. J Biol Chem 2005; 280(23): 22070-80.
  11. Yuan G, Zhang B, Yang S, Jin L, Datta A, Bae S, et al. Novel role of STRAP in progression and metastasis of colorectal cancer through Wnt/beta-catenin signaling. Oncotarget 2016; 7(13): 16023-37.
  12. Huang CJ, Lee CL, Yang SH, Chien CC, Huang CC, Yang RN, et al. Upregulation of the growth arrest-specific-2 in recurrent colorectal cancers, and its susceptibility to chemotherapy in a model cell system. Biochim Biophys Acta 2016; 1862(7): 1345-53.
  13. Guzinska-Ustymowicz K, Pryczynicz A, Kemona A, Czyzewska J. Correlation between proliferation markers: PCNA, Ki-67, MCM-2 and antiapoptotic protein Bcl-2 in colorectal cancer. Anticancer Res 2009; 29(8): 3049-52.
  14. Chang CC, Huang CC, Yang SH, Chien CC, Lee CL, Huang CJ. Data on clinical significance of GAS2 in colorectal cancer cells. Data Brief 2016; 8: 82-6.
  15. Zhou H, Ge Y, Sun L, Ma W, Wu J, Zhang X, et al. Growth arrest specific 2 is up-regulated in chronic myeloid leukemia cells and required for their growth. PLoS One 2014; 9(1): e86195.
  16. Murugesan SN, Yadav BS, Maurya PK, Chaudhary A, Singh S, Mani A. Expression and network analysis of YBX1 interactors for identification of new drug targets in lung adenocarcinoma. J Genomics 2018; 6: 103-12.
  17. Oz S, Maercker C, Breiling A. Embryonic carcinoma cells show specific dielectric resistance profiles during induced differentiation. PLoS One 2013; 8(3): e59895.
  18. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25(4): 402-8.
  19. Linnekamp JF, Wang X, Medema JP, Vermeulen L. Colorectal cancer heterogeneity and targeted therapy: A case for molecular disease subtypes. Cancer Res 2015; 75(2): 245-9.
  20. Huang W, Zhou W, Saberwal G, Konieczna I, Horvath E, Katsoulidis E, et al. Interferon consensus sequence binding protein (ICSBP) decreases beta-catenin activity in myeloid cells by repressing GAS2 transcription. Mol Cell Biol 2010; 30(19): 4575-94.
  21. Jamieson CH, Ailles LE, Dylla SJ, Muijtjens M, Jones C, Zehnder JL, et al. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML. N Engl J Med 2004; 351(7): 657-67.