Original Articles

Alteration in the expression of PELP1 and c-Src genes in tumor tissue of colorectal cancer patients

Abstract

Objectives: The genetic and environmental factors have crucial role in colorectal cancer (CRC) pathogenesis. Due to important role of proline , glutamic acid, and leucine-rich protein 1 (PELP1)    and c-Src genes in different types of malignancy, this study aimed to investigate the expression levels of the PELP1 and c-Src genes in tumor versus matched non-cancerous margin tissues of patients with CRC, and further evaluate their capacity as potential diagnostic biomarkers.

Methods: The gene expression of PELP1 and c-Src in 31 tumor tissues and 31 non-cancerous margin tissues of CRC subjects was analyzed by the Real-Time PCR. Moreover, Receiver Operating Characteristic (ROC) curve analysis was utilized for the determination of these genes' RNA levels as potential biomarkers.

Results: Our findings indicated the increased PELP1 (P=0.016) and c-Src (P=0.006) gene expression in tumor tissues, compared to non-cancerous margin tissues in CRC. The result of ROC analysis showed that the area under the curve (AUC)  for PELP1 and c-Src were 0.673 (Cut off:7.74, sensitivity:0.714, specificity:0.615) and 0.731 (Cut off:16.04, sensitivity: 0.857, specificity: 0.653), respectively.

Conclusion: The higher expression of c-Src and PELP1 genes in tumor tissues compared to non-cancerous margin tissues indicated that these genes are critical components of the signaling pathways involved in CRC pathogenesis. Furthermore, the findings revealed that studied genes can have a potential for diagnosis purposes in CRC. 

1. Sedlak JC, Yilmaz OH, Roper J. Metabolism and Colorectal Cancer. Annu Rev Pathol. 2023;18(1):467-92. https://doi.org/10.1146/annurev-pathmechdis-031521-041113.
2. Rebuzzi F, Ulivi P, Tedaldi G. Genetic Predisposition to Colorectal Cancer: How Many and Which Genes to Test? Int J Mol Sci. 2023;24(3):2137. https://doi.org/10.3390/ijms24032137
3. Ning Z, Zhang Y, Chen H, Wu J, Song T, Wu Q, Liu F. PELP1 suppression inhibits colorectal cancer through c‐Src downregulation. Oxid Med Cell Longev. 2014;2014(1):193523. https://doi.org/10.1155/2014/193523
4. Wang J, Qiang Z, Song S, Shi L, Ma C, Tan X, et al. Temporal expression of Pelp1 during proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells. PLoS One. 2013;8(10):e75477. https://doi.org/10.1371/journal.pone.0075477.
5. Yan Y, Zeng W, Song S, Zhang F, He W, Liang W, Niu Z. Vitamin C induces periodontal ligament progenitor cell differentiation via activation of ERK pathway mediated by PELP1. Protein Cell. 2013;4(8):620-7. https://doi.org/10.3389/fonc.2019.01423
6. Wang J, Zhu Q, Song S, Dong J, Shi L, Tao R, et al. Increased PELP1 expression in rat periodontal ligament tissue in response to estrogens treatment. J Mol Histol. 2013;44(3):347-56. https://doi.org/10.1007/s10735-013-9490-y.
7. Wang X, Ying W, Liang L. PELP1 expressed in non-small cell lung cancer and promotes tumor cell proliferation, metastasis, and drug resistance through MAPK signaling pathway. 2020. https://doi.org/10.21203/rs.3.rs-40995/v2
8. Fadlallah H, El Masri J, Fakhereddine H, Youssef J, Chemaly C, Doughan S, Abou-Kheir W. Colorectal cancer: Recent advances in management and treatment. World j Clin Oncol. 2024;15(9):1136-56. https://doi.org/10.5306/wjco.v15.i9.1136.
9. Raji L, Tetteh A, Amin A. Role of c-Src in Carcinogenesis and Drug Resistance. Cancers. 2023;16(1). https://doi.org/10.3390/cancers16010032.
10. Jin W. Regulation of Src Family Kinases during Colorectal Cancer Development and Its Clinical Implications. Cancers. 2020;12(5):1339. https://doi.org/10.3390/cancers12051339.
11. Yan H, Sun Y, Wu Q, Wu Z, Hu M, Sun Y, et al. PELP1 suppression inhibits gastric cancer through downregulation of c-Src-PI3K-ERK pathway. Front Oncol. 2020;9:1423. https://doi.org/10.3389/fonc.2019.01423
12. Grivas PD, Tzelepi V, Sotiropoulou-Bonikou G, Kefalopoulou Z, Papavassiliou AG, Kalofonos H. Expression of ERalpha, ERbeta and co-regulator PELP1/MNAR in colorectal cancer: prognostic significance and clinicopathologic correlations. Cell Oncol. 2009;31(3):235-47. https://doi.org/10.3233/CLO-2009-0467.
13. Tzelepi V, Grivas P, Kefalopoulou Z, Kalofonos H, Varakis JN, Sotiropoulou-Bonikou G. Expression of estrogen receptor co-regulators NCoR and PELP1 in epithelial cells and myofibroblasts of colorectal carcinomas: cytoplasmic translocation of NCoR in epithelial cells correlates with worse prognosis. Virchows Archiv. 2009;454:41-53. https://doi.org/10.1007/s00428-008-0708-4
14. Simatou A, Simatos G, Goulielmaki M, Spandidos DA, Baliou S, Zoumpourlis V. Historical retrospective of the SRC oncogene and new perspectives (Review). Mol Clin Oncol. 2020;13(4):21. https://doi.org/10.3892/mco.2020.2091.
15. Raji L, Tetteh A, Amin A. Role of c-Src in Carcinogenesis and Drug Resistance. Cancers. 2023;16(1):32. https://doi.org/10.3390/cancers16010032.
16. Chen J, Elfiky A, Han M, Chen C, Saif MW. The role of Src in colon cancer and its therapeutic implications. Clin Colorectal Cancer. 2014;13(1):5-13. https://doi.org/10.1016/j.clcc.2013.10.003
17. Arvelo F, Sojo F, Cotte C. Tumour progression and metastasis. Ecancermedicalscience. 2016;10:617. https://doi.org/10.3332/ecancer.2016.617.
18. Zhang H, Shen Z, Zhou Y, Zhang Z, Wang Q, Zhang M, et al. Downregulation of miR-654-3p in Colorectal Cancer Indicates Poor Prognosis and Promotes Cell Proliferation and Invasion by Targeting SRC. Front Genet. 2020;11:577948. https://doi.org/10.3389/fgene.2020.577948.
19. Martinez-Perez J, Lopez-Calderero I, Saez C, Benavent M, Limon ML, Gonzalez-Exposito R, et al. Prognostic relevance of Src activation in stage II-III colon cancer. Hum Pathol. 2017;67:119-25. https://doi.org/10.1016/j.humpath.2017.05.025.
20. Englert-Golon M, Andrusiewicz M, Żbikowska A, Chmielewska M, Sajdak S, Kotwicka M. Altered expression of ESR1, ESR2, PELP1 and c-SRC genes is associated with ovarian cancer manifestation. Int J Mol Sci. 2021;22(12):6216. https://doi.org/10.3390/ijms22126216
21. Liu W, Yue F, Zheng M, Merlot A, Bae DH, Huang M, et al. The proto-oncogene c-Src and its downstream signaling pathways are inhibited by the metastasis suppressor, NDRG1. Oncotarget. 2015;6(11):8851-74. https://doi.org/10.18632/oncotarget.3316.
Files
IssueVol 3 No 4 (2025) QRcode
SectionOriginal Articles
Keywords
c-Src PELP1 Colorectal Cancer Gene expression
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Lotfi N, Babajani F, Roghani SA, Kakavand A, Goodarzi MT, Asadi S. Alteration in the expression of PELP1 and c-Src genes in tumor tissue of colorectal cancer patients. ABI. 2025;3(4):248-254.