Oncology: Diagnosis, Treatment and Prevention

Function and clinical significance of circular RNA circGAS5 in plasma of patients with chemoresistant rectal cancer

  • Zihao PAN ,
  • Jiatong LIN ,
  • Meiyu JIANG ,
  • Xiaoyan OU ,
  • Zejian Lü
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  • Department of Gastrointestinal Surgery,Department of General Surgery,Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou 510080,Guangdong,China

Received date: 2026-03-26

  Online published: 2026-06-30

Abstract

Objective To investigate the expression level of circGAS5 in the peripheral blood of patients with chemotherapy-resistant rectal cancer and to explore its role in chemotherapy resistance as well as its clinical value in the diagnosis of chemotherapy resistance. Methods A circRNA microarray was initially carried out to screen for circGAS5 as a target associated with chemotherapy resistance in rectal cancer. Subsequently, CCK-8 and colony formation assays were performed in tumor cells to explore its influence on the malignant phenotype of chemotherapy resistance. Clinically, 44 patients with chemotherapy-resistant rectal cancer and 108 patients with chemotherapy-sensitive rectal cancer were recruited. The expression level of circGAS5 in plasma was measured using droplet digital polymerase chain reaction (ddPCR). Statistical analyses, including the t-test, chi-square test, univariate and multivariate logistic regression analyses, and the receiver operating characteristic (ROC) curve, were utilized to assess the relationship between circGAS5 and chemotherapy resistance in rectal cancer. Results In vitro experiments demonstrated that the expression of circGAS5 was significantly up-regulated in chemotherapy-resistant cells and their culture media, and it was accompanied by enhanced structural stability. Clinical data analysis indicated that the plasma expression levels of circGAS5 were significantly higher in patients with chemotherapy-resistant rectal cancer than in those with chemotherapy-sensitive disease (P < 0.001). Multivariate logistic regression analysis further confirmed that high plasma circGAS5 expression was an independent risk factor for chemotherapy resistance (OR = 3.41, 95%CI: 2.15 - 5.41, P < 0.001). ROC curve analysis showed a favorable diagnostic performance with an area under the curve (AUC) of 0.827 9, and the AUC remained stable in subgroup analyses, suggesting the robust diagnostic value of circGAS5. Functional assays showed that circGAS5 promoted the progression of the malignant phenotype associated with chemotherapy resistance in rectal cancer cells. Conclusion circGAS5 may serve as a promising biomarker in peripheral blood for evaluating chemotherapy resistance in rectal cancer.

Cite this article

Zihao PAN , Jiatong LIN , Meiyu JIANG , Xiaoyan OU , Zejian Lü . Function and clinical significance of circular RNA circGAS5 in plasma of patients with chemoresistant rectal cancer[J]. The Journal of Practical Medicine, 2026 , 42(12) : 2153 -2160 . DOI: 10.3969/j.issn.1006-5725.2026.12.009

References

[1] 中华医学会外科学分会结直肠外科学组, 中国研究型医院学会结直肠肛门外科专业委员会, 中华医学会消化内镜学分会超级微创协作组中华医学会外科学分会结直肠外科学组, 等. 直肠癌新辅助治疗达临床完全缓解或近临床完全缓解后局部切除策略专家共识(2026版)[J]. 中华胃肠外科杂志, 2026, 29(3): 258-274. doi: 10.3760/cma.j.cn441530-20260113-00031 .
[2] SIEGEL R L, WAGLE N S, CERCEK A, et al. Colorectal cancer statistics, 2023[J]. CA A Cancer J Clin, 2023, 73(3): 233-254. doi:10.3322/caac.21772 .
[3] 结直肠早癌全程管理指南制定工作组,中华医学会外科学分会结直肠外科学组,广东省医院协会结直肠外科专委会. 早期结直肠癌全程管理指南(2025版)[J]. 中华胃肠外科杂志,2025,28(12):1351-1368. doi:10.3760/cma.j.cn441530-20251012-00378
[4] 中国医师协会结直肠肿瘤专委会机器人外科学组. 机器人结直肠癌手术专家共识(2025版)[J]. 中华胃肠外科杂志,2025,28(8):845-864. doi:10.3760/cma.j.cn441530-20250728-00285 .
[5] XIE Y H, CHEN Y X, FANG J Y. Comprehensive review of targeted therapy for colorectal cancer[J]. Sig Transduct Target Ther, 2020, 5: 22. doi:10.1038/s41392-020-0116-z .
[6] YOSHINO T, ARNOLD D, TANIGUCHI H, et al. Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: A JSMO–ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS[J]. Ann Oncol, 2018, 29(1): 44-70. doi:10.1093/annonc/mdx738 .
[7] HU F, SONG D, YAN Y, et al. IL-6 regulates autophagy and chemotherapy resistance by promoting BECN1 phosphorylation[J]. Nat Commun, 2021, 12: 3651. doi:10.1038/s41467-021-23923-1 .
[8] ABDELMAKSOUD N M, ABULSOUD A I, DOGHISH A S, et al. From resistance to resilience: Uncovering chemotherapeutic resistance mechanisms; insights from established models[J]. Biochim Biophys Acta BBA Rev Cancer, 2023, 1878(6): 188993. doi:10.1016/j.bbcan.2023.188993 .
[9] LIN C, MA M, ZHANG Y, et al. Correction to: The N6-methyladenosine modification of circALG1 promotes the metastasis of colorectal cancer mediated by the miR-342-5p/PGF signalling pathway[J]. Mol Cancer, 2022, 21(1): 101. doi:10.1186/s12943-022-01571-3 .
[10] BILLER L H, SCHRAG D. Diagnosis and treatment of metastatic colorectal cancer: A review[J]. Jama, 2021, 325(7): 669. doi:10.1001/jama.2021.0106 .
[11] KRISTENSEN L S, JAKOBSEN T, HAGER H, et al. The emerging roles of circRNAs in cancer and oncology[J]. Nat Rev Clin Oncol, 2022, 19(3): 188-206. doi:10.1038/s41571-021-00585-y .
[12] XIAO M S, AI Y, WILUSZ J E. Biogenesis and functions of circular RNAs come into focus[J]. Trends Cell Biol, 2020, 30(3): 226-240. doi:10.1016/j.tcb.2019.12.004 .
[13] KRISTENSEN L S, ANDERSEN M S, STAGSTED L V W, et al. The biogenesis, biology and characterization of circular RNAs[J]. Nat Rev Genet, 2019, 20(11): 675-691. doi:10.1038/s41576-019-0158-7 .
[14] LIN J, ZHONG W, LYU Z, et al. Circular RNA circTATDN3 promotes the Warburg effect and proliferation in colorectal cancer[J]. Cancer Lett, 2024, 589: 216825. doi:10.1016/j.canlet. 2024.216825 .
[15] PAN Z, CAI J, LIN J, et al. A novel protein encoded by circFNDC3B inhibits tumor progression and EMT through regulating Snail in colon cancer[J]. Mol Cancer, 2020, 19(1): 71. doi:10.1186/s12943-020-01179-5 .
[16] PAN Z, ZHENG J, ZHANG J, et al. A novel protein encoded by exosomal CircATG4B induces oxaliplatin resistance in colorectal cancer by promoting autophagy[J]. Adv Sci, 2022, 9(35): 2204513. doi:10.1002/advs.202204513 .
[17] LIN J, LYU Z, FENG H, et al. CircPDIA3/miR-449a/XBP1 feedback loop curbs pyroptosis by inhibiting palmitoylation of the GSDME-C domain to induce chemoresistance of colorectal cancer[J]. Drug Resist Updat, 2024, 76: 101097. doi:10.1016/j.drup. 2024.101097 .
[18] LIU C X, CHEN L L. Circular RNAs: Characterization, cellular roles, and applications[J]. Cell, 2022, 185(13): 2390. doi:10.1016/j.cell.2022.06.001 .
[19] ZHOU W Y, CAI Z R, LIU J, et al. Circular RNA: Metabolism, functions and interactions with proteins[J]. Mol Cancer, 2020, 19(1): 172. doi:10.1186/s12943-020-01286-3 .
[20] 张顺皓,耿志欣,孙建,等. 环状RNA在结直肠癌中的研究进展[J]. 临床肿瘤学杂志,2024,29(6):605-611. doi:10.3969/j.issn.1009-0460.2024.06.018
[21] 周瑶, 戴乾滨, 龙伟, 等. 强直性脊柱炎患者环状RNA hsa_circ_0001707的表达及意义[J]. 实用医学杂志, 2026, 42(2): 295-302. doi:10.3969/j.issn.1006-5725.2026.02.015 .
[22] 刘杜平, 李国平, 王亮军. 甲胎蛋白、癌胚抗原联合细胞角蛋白19片段在结直肠癌患者中的表达及意义[J]. 医学信息, 2026, 39(4): 18-22. doi:10.3969/j.issn.1006-1959.2026.04.004 .
[23] 文雅星, 郭忠聪. 结直肠癌化疗耐药的影响因素分析及其风险预测列线图模型构建[J]. 临床合理用药, 2025, 18(9): 27-30. doi:10.15887/j.cnki.13-1389/r.2025.09.007 .
[24] CERCEK A, DOS SANTOS FERNANDES G, ROXBURGH C S, et al. Mismatch repair-deficient rectal cancer and resistance to neoadjuvant chemotherapy[J]. Clin Cancer Res, 2020, 26(13): 3271-3279. doi:10.1158/1078-0432.ccr-19-3728 .
[25] PRETTA A, ZIRANU P, GIAMPIERI R, et al. Mismatch Repair system protein deficiency as a resistance factor for locally advanced rectal adenocarcinoma patients receiving neoadjuvant chemo-radiotherapy[J]. Br J Cancer, 2023, 129(10): 1619-1624. doi:10.1038/s41416-023-02444-2 .
[26] 华梅, 翟晓璐, 唐翀, 等. 结直肠癌患者血清microRNA-497的表达及其诊断与预后价值[J]. 实用医学杂志, 2025, 41(22): 3579-3584. doi:10.3969/j.issn.1006-5725.2025.22.016 .
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