en Medical Biology Medical Biology مقاله پژوهشی Original Research Article <p style="text-align: justify;"><span style="font-size:16px;"><span style="font-family:Times New Roman;"><b><span style="background:#2d7f8f"><span style="color:white">Background & Objective:</span></span><b> </b></b><span style="color:black">Gastric cancer (GC) represents a major global health concern, often diagnosed at advanced stages, with limited effective biomarkers for early detection. Long intergenic non-coding RNA p21 (<em>lincRNA-p21</em>) has been implicated in many cancers, yet its role in GC is not fully understood.</span><br> <b><span style="background:#2d7f8f"><span style="color:white"><span style="letter-spacing:-.1pt">&nbsp;Materials & Methods:</span></span></span></b> <span style="color:black">In the current case&ndash;control design, we analyzed the expression of <em>lincRNA-p21</em> in 40 matched pairs of tumor tissues and their adjacent non-tumor counterparts, as well as in a panel of cancer and stem-like cells, including gastric (AGS, MKN45) and esophageal adenocarcinoma (FLO-1, OE-19) cell lines, the human embryonal carcinoma line (NTERA2), human induced pluripotent stem cells (hiPSCs), and mesenchymal stem cells (MSCs). This approach was designed to explore whether <em>lincRNA-p21</em> expression is associated with stemness and tumorigenic potential. Total RNA was extracted, followed by cDNA synthesis and qPCR analysis. Additionally, TCGA data were assessed via the UALCAN platform to evaluate the expression pattern of key cell cycle related genes (<em>CDKN1A, STAT3, CDK2 </em>and<em> E2F1</em>) in GC samples with differing<em> TP53 </em>mutation statuses.</span><br> <b><span lang="EN-IN"><span style="background:#2d7f8f"><span style="color:white">Results: </span></span></span>&nbsp;</b><span style="color:black">A significant reduction in <em>lincRNA-p21</em> expression was identified in tumor tissues compared to non-tumor samples (<em>P</em>=0.01), and its reduced expression was consistent across various malignancy grades. Likewise, GC and stem-like cell lines exhibited lower <em>lincRNA-p21</em> levels relative to normal controls, suggesting a role in suppressing stemness and tumor progression. Furthermore, TCGA analysis revealed significantly elevated <em>STAT3, CDK2</em>, and<em> E2F1</em> expression in both <em>TP53</em>-mutated and wild-type gastric tumors, implicating dysregulation of the <em>lincRNA-p21</em>&ndash;p21&ndash;p53 axis in GC pathogenesis.</span><br> <b><span style="background:#2d7f8f"><span style="color:white">Conclusion: </span></span>&nbsp;</b><span style="color:black">The reduced levels of <em>lincRNA-p21</em>, along with elevated STAT3, CDK2, and E2F1, indicate disrupted cell cycle control in GC. Consistent <em>lincRNA-p21</em> downregulation across malignancy stages suggests its potential as an early prognostic biomarker for GC detection.</span></span></span></p> Gastric Cancer, lincRNA-p21, Cancer Stem Cells, p21-p53 Axis, Cell Cycle Control, Biomarker 325 334 http://journal.zums.ac.ir/browse.php?a_code=A-10-3534-3&slc_lang=en&sid=1 Somayeh Jahandoust m.khalili@zums.ac.ir 5200319475328460085896 5200319475328460085896 No Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran Pourandokht Farhangiyan mitrakhalili@yahoo.com 5200319475328460085897 5200319475328460085897 No Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran Mitra Khalili khalili.mitra@gmail.com 5200319475328460085898 5200319475328460085898 Yes Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran