Colorectal cancer (CRC) ranks as the second most prevalent malignancy globally, highlighting the urgent need for more effective diagnostic and therapeutic strategies, as well as a deeper understanding of its molecular basis. Extensive research has demonstrated that cells actively secrete extracellular vesicles (EVs) to mediate intercellular communication at both proximal and distal sites. In this study, we conducted a comprehensive analysis of the RNA content of small extracellular vesicles (sEVs) secreted into the culture media of five frequently utilised CRC cell lines (RKO, HCT116, HCT15, HT29, and DLD1). RNA sequencing data revealed significant insights into the RNA profiles of these sEVs, identifying nine protein-coding genes and fourteen long non-coding RNA (lncRNA) genes that consistently ranked among the top 30 most abundant across all cell lines. Notably, the genes found in sEVs were highly similar among the cell lines, indicating a conserved molecular signature. Several of these genes have been previously documented in the context of cancer biology, while others represent novel discoveries. These findings provide valuable insights into the molecular cargo of sEVs in CRC, potentially unveiling novel biomarkers and therapeutic targets.

Centre for Molecular Medicine Central European Institute of Technology Masaryk University Kamenice 5 Brno 625 00 Czech Republic

Department of Biology Faculty of Medicine Masaryk University Kamenice 5 Brno 625 00 Czech Republic

Department of Pharmacology and Toxicology Veterinary Research Institute Brno Czech Republic

See more in PubMed

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63. 10.3322/caac.21834. Epub 2024 Apr 4 PMID: 38572751. PubMed

Ayre DC, Elstner M, Smith NC, Moores ES, Hogan AM, Christian SL. Dynamic regulation of CD24 expression and release of CD24-containing microvesicles in immature B cells in response to CD24 engagement. Immunology. 2015;146:217–33. PubMed PMC

Headland SE, Jones HR, Norling LV, Kim A, Souza PR, Corsiero E, et al. Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis. Sci Transl Med. 2015;7:1–13. PubMed PMC

Silva AM, Teixeira JH, Almeida MI, Gonçalves RM, Barbosa MA, Santos SG. Extracellular Vesicles: Immunomodulatory messengers in the context of tissue repair/regeneration. Eur J Pharm Sci. 2017;98:86–95. PubMed

Abdouh M, Floris M, Gao ZH, Arena V, Arena M, Arena GO. Colorectal cancer-derived extracellular vesicles induce transformation of fibroblasts into colon carcinoma cells. J Exp Clin Cancer Res. 2019;38:1–22. PubMed PMC

Keklikoglou I, Cianciaruso C, Güç E, Squadrito ML, Spring LM, Tazzyman S, et al. Chemotherapy elicits pro-metastatic extracellular vesicles in breast cancer models. Nat Cell Biol. 2019;21:190–202. PubMed PMC

Yáñez-Mó M, Siljander PRM, Andreu Z, Zavec AB, Borràs FE, Buzas EI, et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles. 2015;4:1–60. PubMed PMC

Hosseini M, Khatamianfar S, Hassanian SM, Nedaeinia R, Shafiee M, Maftouh M, et al. Exosome-Encapsulated microRNAs as Potential Circulating Biomarkers in Colon Cancer. Curr Pharm Des. 2016;23:1705–9. PubMed

Nedaeinia R, Manian M, Jazayeri MH, Ranjbar M, Salehi R, Sharifi M, et al. Circulating exosomes and exosomal microRNAs as biomarkers in gastrointestinal cancer. Cancer Gene Ther. 2017;24:48–56. PubMed

Maacha S, Bhat AA, Jimenez L, Raza A, Haris M, Uddin S, et al. Extracellular vesicles-mediated intercellular communication: Roles in the tumor microenvironment and anti-cancer drug resistance. Mol Cancer. 2019;18:1–16. PubMed PMC

Rahmati S, Moeinafshar A, Rezaei N. The multifaceted role of extracellular vesicles (EVs) in colorectal cancer: metastasis, immune suppression, therapy resistance, and autophagy crosstalk. J Transl Med. 2024;22:1–34. PubMed PMC

Popěna I, Abols A, Saulite L, Pleiko K, Zandberga E, Jěkabsons K, et al. Effect of colorectal cancer-derived extracellular vesicles on the immunophenotype and cytokine secretion profile of monocytes and macrophages. Cell Commun Signal. 2018;16:1–12. PubMed PMC

Shao Y, Chen T, Zheng X, Yang S, Xu K, Chen X, et al. Colorectal cancer-derived small extracellular vesicles establish an inflammatory premetastatic niche in liver metastasis. Carcinogenesis. 2018;39:1368–79. PubMed

Al-Nedawi K, Meehan B, Kerbel RS, Allison AC, Rak A. Endothelial expression of autocrine VEGF upon the uptake of tumor-derived microvesicles containing oncogenic EGFR. Proc Natl Acad Sci U S A. 2009;106:3794–9. PubMed PMC

Ren D, Lin B, Zhang X, Peng Y, Ye Z, Ma Y, et al. Maintenance of cancer stemness by miR-196b-5p contributes to chemoresistance of colorectal cancer cells via activating STAT3 signaling pathway. Oncotarget. 2017;8:49807–23. PubMed PMC

Yang Y, Zhang J, Zhang W, Wang Y, Zhai Y, Li Y, et al. A liquid biopsy signature of circulating extracellular vesicles-derived RNAs predicts response to first line chemotherapy in patients with metastatic colorectal cancer. Mol Cancer. 2023;22:1–7. PubMed PMC

Wada Y, Nishi M, Yoshikawa K, Takasu C, Tokunaga T, Nakao T, et al. Circulating Exosomal MicroRNA Signature Predicts Peritoneal Metastasis in Patients with Advanced Gastric Cancer. Ann Surg Oncol. 2024;31:5997–6006. PubMed

Jafarpour S, Ahmadi S, Mokarian F, Sharifi M, Ghobakhloo S, Yazdi M, et al. MSC-derived exosomes enhance the anticancer activity of drugs in 3D spheroid of breast cancer cells. J Drug Deliv Sci Technol. 2024;92:105375.

Hu W, Liu C, Bi ZY, Zhou Q, Zhang H, Li LL, et al. Comprehensive landscape of extracellular vesicle-derived RNAs in cancer initiation, progression, metastasis and cancer immunology. Mol Cancer. 2020;19:1–23. PubMed PMC

Whiteside TL. Tumor-Derived Exosomes and Their Role in Cancer Progression. Adv Clin Chem. 2016;74:103–41. PubMed PMC

Welsh JA, Goberdhan DCI, O’Driscoll L, Buzas EI, Blenkiron C, Bussolati B, et al. Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches. J Extracell vesicles. 2024;13:e12404. PubMed PMC

Boudna M, Machackova T, Vychytilova-Faltejskova P, Trachtova K, Bartosova R, Catela Ivkovic T, et al. Investigation of long non-coding RNAs in extracellular vesicles from low-volume blood serum specimens of colorectal cancer patients. Clin Exp Med. 2024;24:67. PubMed PMC

Lobb RJ, Becker M, Wen SW, Wong CSF, Wiegmans AP, Leimgruber A, et al. Optimized exosome isolation protocol for cell culture supernatant and human plasma. J Extracell Vesicles. 2015;4:1–11. PubMed PMC

Rautajoki KJ, Jaatinen S, Tiihonen AM, Annala M, Vuorinen EM, Kivinen A, et al. PTPRD and CNTNAP2 as markers of tumor aggressiveness in oligodendrogliomas. Sci Rep. 2022;12:12. PubMed PMC

Alagoda S, Wimalaratna S, Herath TM. Occult bowel cancer presenting as Morvan syndrome. BMJ Case Rep. 2023;16:e256407. PubMed PMC

Nishida N, Nagahara M, Sato T, Mimori K, Sudo T, Tanaka F, et al. Microarray analysis of colorectal cancer stromal tissue reveals upregulation of two oncogenic miRNA clusters. Clin Cancer Res. 2012;18:3054–70. PubMed

Zhou J, Xie Z, Cui P, Cui P, Su Q, Zhang Y, et al. SLC1A1, SLC16A9, and CNTN3 are potential biomarkers for the occurrence of colorectal cancer. Biomed Res Int. 2020;2020:1204605. PubMed PMC

Molnár B, Galamb O, Péterfia B, Wichmann B, Csabai I, Bodor A, et al. Gene promoter and exon DNA methylation changes in colon cancer development - mRNA expression and tumor mutation alterations. BMC Cancer. 2018;18:1–14. PubMed PMC

Kok-Sin T, Mokhtar NM, Hassan NZA, Sagap I, Rose IM, Harun R, et al. Identification of diagnostic markers in colorectal cancer via integrative epigenomics and genomics data. Oncol Rep. 2015;34:22. PubMed PMC

Gielata M, Karpińska K, Pieczonka T, Kobielak A. Emerging roles of the α-catenin family member α-catulin in development, homeostasis and cancer progression. Int J Mol Sci. 2022;23:11962. PubMed PMC

Smith DI, Zhu Y, McAvoy S, Kuhn R. Common fragile sites, extremely large genes, neural development and cancer. Cancer Lett. 2006;232:48–57. PubMed

He B, Li T, Guan L, Liu FE, Chen XM, Zhao J, et al. CTNNA3 is a tumor suppressor in hepatocellular carcinomas and is inhibited by miR-425. Oncotarget. 2016;7:8078. PubMed PMC

Skuja E, Butane D, Nakazawa-Miklasevica M, Daneberga Z, Purkalne G, Miklasevics E. Deletions in metastatic colorectal cancer with chromothripsis. Exp Oncol. 2019;41:323–7. PubMed

Keane S, Herring M, Rolny P, Wettergren Y, Ejeskär K. Inflammation suppresses DLG2 expression decreasing inflammasome formation. J Cancer Res Clin Oncol. 2022;148:2295–311. PubMed PMC

Sonoshita M, Itatani Y, Kakizaki F, Sakimura K, Terashima T, Katsuyama Y, et al. Promotion of colorectal cancer invasion and metastasis through activation of NOTCH–DAB1–ABL–RHOGEF protein TRIO. Cancer Discov. 2015;5:198–211. PubMed

Serrano-Morales JM, Vázquez-Carretero MD, Peral MJ, Ilundáin AA, García-Miranda P. Reelin-Dab1 signaling system in human colorectal cancer. Mol Carcinog. 2017;56:712–21. PubMed

Hansen TF, Nielsen BS, Sørensen FB, Johnsson A, Jakobsen A. Epidermal growth factor-like domain 7 predicts response to first-line chemotherapy and bevacizumab in patients with metastatic colorectal cancer. Mol Cancer Ther. 2014;13:2238–45. PubMed

He G, Li W, Zhao W, Men H, Chen Q, Hu J, et al. Formin-like 2 promotes angiogenesis and metastasis of colorectal cancer by regulating the EGFL6/CKAP4/ERK axis. Cancer Sci. 2023;114:2014. PubMed PMC

Hasegawa K, Kuwata K, Yoshitake J, Shimomura S, Uchida K, Shibata T. Extracellular vesicles derived from inflamed murine colorectal tissue induce fibroblast proliferation via epidermal growth factor receptor. FEBS J. 2021;288:1906–17. PubMed

Príncipe C, de Sousa IJD, Prazeres H, Soares P, Lima RT. LRP1B: A Giant Lost in Cancer Translation. Pharmaceuticals. 2021;14:836. PubMed PMC

Ge W, Hu H, Cai W, Xu J, Hu W, Weng X, et al. High-risk Stage III colon cancer patients identified by a novel five-gene mutational signature are characterized by upregulation of IL-23A and gut bacterial translocation of the tumor microenvironment. Int J Cancer. 2020;146:2027–35. PubMed

Wolff RK, Hoffman MD, Wolff EC, Herrick JS, Sakoda LC, Samowitz WS, et al. Mutation analysis of adenomas and carcinomas of the colon: Early and late drivers. Genes, Chromosom Cancer. 2018;57:366–76. PubMed PMC

Cao H, Liu X, Chen Y, Yang P, Huang T, Song L, et al. Circulating Tumor DNA Is Capable of Monitoring the Therapeutic Response and Resistance in Advanced Colorectal Cancer Patients Undergoing Combined Target and Chemotherapy. Front Oncol. 2020;10:466. PubMed PMC

Wang Z, Sun P, Gao C, Chen J, Li J, Chen Z, et al. Down-regulation of LRP1B in colon cancer promoted the growth and migration of cancer cells. Exp Cell Res. 2017;357:1–8. PubMed

Bahrami A, Amerizadeh F, ShahidSales S, Khazaei M, Ghayour-Mobarhan M, Sadeghnia HR, et al. Therapeutic Potential of Targeting Wnt/β-Catenin Pathway in Treatment of Colorectal Cancer: Rational and Progress. J Cell Biochem. 2017;118:1979–83. PubMed

Hsu HC, Lapke N, Chen SJ, Lu YJ, Jhou RS, Yeh CY, et al. PTPRT and PTPRD Deleterious Mutations and Deletion Predict Bevacizumab Resistance in Metastatic Colorectal Cancer Patients. Cancers (Basel). 2018;10:10. PubMed PMC

Liu K, Cui Y, Li H, Mi J, Wang H, Zhuang Y, et al. The mechanism investigation of mutation genes in liver and lung metastasis of colorectal cancer by using NGS technique. Crit Rev Oncol Hematol. 2023;188:104057. PubMed

Liang Y, Sun HX, Ma B, Meng QK. Identification of a genomic instability-related long noncoding RNA prognostic model in colorectal cancer based on bioinformatic analysis. Dis Markers. 2022;2022:4556585. PubMed PMC

Sengupta N, Yau C, Sakthianandeswaren A, Mouradov D, Gibbs P, Suraweera N, et al. Analysis of colorectal cancers in British Bangladeshi identifies early onset, frequent mucinous histotype and a high prevalence of RBFOX1 deletion. Mol Cancer. 2013;12:1–1. PubMed PMC

Zhou D, Yang L, Zheng L, Ge W, Li D, Zhang Y, et al. Exome capture sequencing of adenoma reveals genetic alterations in multiple cellular pathways at the early stage of colorectal tumorigenesis. PLoS One. 2013;8:e53310. PubMed PMC

Mampaey E, Fieuw A, Van Laethem T, Ferdinande L, Claes K, Ceelen W, et al. Focus on 16p13.3 locus in colon cancer. PLoS One. 2015;10:e0131421. PubMed PMC

Mori Y, Kataoka H, Miura Y, Kawaguchi M, Kubota E, Ogasawara N, et al. Subcellular localization of ATBF1 regulates MUC5AC transcription in gastric cancer. Int J Cancer. 2007;121:241–7. PubMed

Krishn SR, Kaur S, Smith LM, Johansson SL, Jain M, Patel A, et al. Mucins and associated glycan signatures in colon adenoma-carcinoma sequence: Prospective pathological implication(s) for early diagnosis of colon cancer. Cancer Lett. 2016;374:304–14. PubMed PMC

Pothuraju R, Rachagani S, Krishn SR, Chaudhary S, Nimmakayala RK, Siddiqui JA, et al. Molecular implications of MUC5AC-CD44 axis in colorectal cancer progression and chemoresistance. Mol Cancer. 2020;19:1–14. PubMed PMC

Jing N, Huang T, Guo H, Yang J, Li M, Chen Z, et al. LncRNA CASC15 promotes colon cancer cell proliferation and metastasis by regulating the miR-4310/LGR5/Wnt/ß-catenin signaling pathway. Mol Med Rep. 2018;18:2269–76. PubMed

Fernando TR, Contreras JR, Zampini M, Rodriguez-Malave NI, Alberti MO, Anguiano J, et al. The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia. Mol Cancer. 2017;16:1–15. PubMed PMC

He T, Zhang L, Kong Y, Huang Y, Zhang Y, Zhou D, et al. Long non-coding RNA CASC15 is upregulated in hepatocellular carcinoma and facilitates hepatocarcinogenesis. Int J Oncol. 2017;51:1722–30. PubMed PMC

Lin H, Xu X, Chen K, Fu Z, Wang S, Chen Y, et al. LncRNA CASC15, MiR-23b Cluster and SMAD3 form a Novel Positive Feedback Loop to promote Epithelial-Mesenchymal Transition and Metastasis in Ovarian Cancer. Int J Biol Sci. 2022;18:1989–2002. PubMed PMC

Lessard L, Liu M, Marzese DM, Wang H, Chong K, Kawas N, et al. The CASC15 Long Intergenic Noncoding RNA Locus Is Involved in Melanoma Progression and Phenotype Switching. J Invest Dermatol. 2015;135:2464–74. PubMed PMC

Yan J, Chen D, Chen X, Sun X, Dong Q, Hu C, et al. Downregulation of lncRNA CCDC26 contributes to imatinib resistance in human gastrointestinal stromal tumors through IGF-1R upregulation. Brazilian J Med Biol Res. 2019;52:1–8. PubMed PMC

Cao K, Li M, Miao J, Lu X, Kang X, Zhu H, et al. CCDC26 knockdown enhances resistance of gastrointestinal stromal tumor cells to imatinib by interacting with c-KIT. Am J Transl Res. 2018;10:274–82. PubMed PMC

Hatanaka Y, Niinuma T, Kitajima H, Nishiyama K, Maruyama R, Ishiguro K, et al. DLEU1 promotes oral squamous cell carcinoma progression by activating interferon-stimulated genes. Sci Rep. 2021;11:1–12. PubMed PMC

Zhang S, Guan Y, Liu X, Ju M, Zhang Q. Long non-coding RNA DLEU1 exerts an oncogenic function in non-small cell lung cancer. Biomed Pharmacother. 2019;109:985–90. PubMed

Pang B, Sui S, Wang Q, Wu J, Yin Y, Xu S. Upregulation of DLEU1 expression by epigenetic modification promotes tumorigenesis in human cancer. J Cell Physiol. 2019;234:17420–32. PubMed

Liu T, Han Z, Li H, Zhu Y, Sun Z, Zhu A. LncRNA DLEU1 contributes to colorectal cancer progression via activation of KPNA3. Mol Cancer. 2018;17:1–13. PubMed PMC

Hu N, Ji H. N6-methyladenosine (m6A)-mediated up-regulation of long noncoding RNA LINC01320 promotes the proliferation, migration, and invasion of gastric cancer via miR495-5p/RAB19 axis. Bioengineered. 2021;12:4081–91. PubMed PMC

Fang X, Xu Y, Li K, Liu P, Zhang H, Jiang Y, et al. Exosomal lncRNA PCAT1 promotes tumor circulating cell-mediated colorectal cancer liver metastasis by regulating the activity of the miR-329–3p/Netrin-1-CD146 Complex. J Immunol Res. 2022;2022:9916228. PubMed PMC

Bi M, Yu H, Huang B, Tang C. Long non-coding RNA PCAT-1 over-expression promotes proliferation and metastasis in gastric cancer cells through regulating CDKN1A. Gene. 2017;626:337–43. PubMed

Prensner JR, Chen W, Han S, Iyer MK, Cao Q, Kothari V, et al. The Long Non-Coding RNA PCAT-1 Promotes Prostate Cancer Cell Proliferation through cMyc. Neoplasia (United States). 2014;16:900–8. PubMed PMC

Domvri K, Petanidis S, Anestakis D, Porpodis K, Bai C, Zarogoulidis P, et al. Exosomal lncRNA PCAT-1 promotes Kras-associated chemoresistance regulation. Oncotarget. 2020;11:2847–62. PubMed PMC

Ge X, Chen Y, Liao X, Liu D, Li F, Ruan H, et al. Overexpression of long noncoding RNA PCAT-1 is a novel biomarker of poor prognosis in patients with colorectal cancer. Med Oncol. 2013;30:1–7. PubMed

Qiao L, Liu X, Tang Y, Zhao Z, Zhang J, Feng Y. Down regulation of the long non-coding RNA PCAT-1 induced growth arrest and apoptosis of colorectal cancer cells. Life Sci. 2017;188:37–44. PubMed

Barbagallo C, Brex D, Caponnetto A, Cirnigliaro M, Scalia M, Magnano A, et al. LncRNA UCA1, Upregulated in CRC Biopsies and Downregulated in Serum Exosomes, Controls mRNA Expression by RNA-RNA Interactions. Mol Ther Nucleic Acids. 2018;12:229–41. PubMed PMC

Fearon ER. Molecular genetics of colorectal cancer. Annu Rev Pathol Mech Dis. 2011;6:479–507. PubMed

Fang JY, Richardson BC. The MAPK signalling pathways and colorectal cancer. Lancet Oncol. 2005;6:322–7. PubMed

Zhang N, Ng AS, Cai S, Li Q, Yang L, Kerr D. Novel therapeutic strategies: targeting epithelial–mesenchymal transition in colorectal cancer. Lancet Oncol. 2021;22:e358–68. PubMed

White BD, Chien AJ, Dawson DW. Dysregulation of Wnt/β-catenin signaling in gastrointestinal cancers. Gastroenterology. 2012;142:219–32. PubMed PMC

Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527:329–35. PubMed PMC

Van Niel G, D’Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles. Nat Rev Mol Cell Biol. 2018;19:213–28. PubMed

Crivelli SM, Giovagnoni C, Zhu Z, Tripathi P, Elsherbini A, Quadri Z, et al. Function of ceramide transfer protein for biogenesis and sphingolipid composition of extracellular vesicles. J Extracell Vesicles. 2022;11:11. PubMed PMC

Rai A, Greening DW, Xu R, Suwakulsiri W, Simpson RJ. Exosomes derived from the human primary colorectal cancer cell line SW480 orchestrate fibroblast-led cancer invasion. Proteomics. 2020;20:2000016. PubMed

Zanetti-Domingues LC, Bonner SE, Martin-Fernandez ML, Huber V. Mechanisms of Action of EGFR Tyrosine Kinase Receptor Incorporated in Extracellular Vesicles. Cells. 2020;9:1–31. PubMed PMC

Wan YH, Liu QS, Wan SS, Wang RW. Colorectal cancer-derived exosomes and modulation KRAS signaling. Clin Transl Oncol. 2022;24:2074–80. PubMed

Zhu G, Pei L, Xia H, Tang Q, Bi F. Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer. Mol Cancer. 2021;20:1–17. PubMed PMC

Sheffels E, Sealover NE, Wang C, Kim DH, Vazirani IA, Lee E, et al. Oncogenic RAS isoforms show a hierarchical requirement for the guanine nucleotide exchange factor SOS2 to mediate cell transformation. Sci Signal. 2018;11:1–15. PubMed PMC

Zhang YL, Wang RC, Cheng K, Ring BZ, Su L. Roles of Rap1 signaling in tumor cell migration and invasion. Cancer Biol Med. 2017;14:90–9. PubMed PMC

Shirakawa R, Horiuchi H. Ral GTPases: Crucial mediators of exocytosis and tumourigenesis. J Biochem. 2015;157:285–99. PubMed

Stevens PD, Wen YA, Xiong X, Zaytseva YY, Li AT, Wang C, et al. Erbin suppresses KSR1-mediated RaS/RAF signaling and tumorigenesis in colorectal cancer. Cancer Res. 2018;78:4839–52. PubMed PMC

Matsuda Y, Ueda J, Ishiwata T. Fibroblast Growth Factor Receptor 2: Expression, Roles, and Potential As a Novel Molecular Target for Colorectal Cancer. Patholog Res Int. 2012;2012:1–8. PubMed PMC

Sekharam M, Zhao H, Sun M, Fang Q, Zhang Q, Yuan Z, et al. Insulin-like Growth Factor 1 Receptor Enhances Invasion and Induces Resistance to Apoptosis of Colon Cancer Cells through the Akt/Bcl-xL Pathway. Cancer Res. 2003;63:7708–16. PubMed

Li L, Chen Q, Yu Y, Chen H, Lu M, Huang Y, et al. RKI-1447 suppresses colorectal carcinoma cell growth via disrupting cellular bioenergetics and mitochondrial dynamics. J Cell Physiol. 2020;235:254–66. PubMed

Carter JH, Cottrell CE, McNulty SN, Vigh-Conrad KA, Lamp S, Heusel JW, et al. FGFR2 amplification in colorectal adenocarcinoma. Cold Spring Harb Mol case Stud. 2017;3:1–12. PubMed PMC

Deng F, Peng L, Li Z, Tan G, Liang E, Chen S, et al. YAP triggers the Wnt/β-catenin signalling pathway and promotes enterocyte self-renewal, regeneration and tumorigenesis after DSS-induced injury. Cell Death Dis. 2018;9:9. PubMed PMC

Rao C, Lin SL, Ruan WJ, Wen H, Wu DJ, Deng H. High expression of IGFBP7 in fibroblasts induced by colorectal cancer cells is co-regulated by TGF-β and Wnt signaling in a Smad2/3-Dvl2/3-dependent manner. PLoS ONE. 2014;9:1–9. PubMed PMC

Wang C, Yue Y, Shao B, Qiu Z, Mu J, Tang J, et al. Dickkopf-related protein 2 is epigenetically inactivated and suppresses colorectal cancer growth and tumor metastasis by antagonizing Wnt/β-catenin signaling. Cell Physiol Biochem. 2017;41:1709–24. PubMed

Foda AARM, Mohammad MA, Abdel-Aziz A, El-Hawary AK. Relation of glypican-3 and E-cadherin expressions to clinicopathological features and prognosis of mucinous and non-mucinous colorectal adenocarcinoma. Tumor Biol. 2015;36:4671–9. PubMed

Conboy CB, Velez-Reyes GL, Rathe SK, Abrahante JE, Temiz NA, Burns MB, et al. R-Spondins 2 and 3 Are Overexpressed in a Subset of Human Colon and Breast Cancers. DNA Cell Biol. 2021;40:70–9. PubMed PMC

Segura AVC, Sotomayor MBV, Román AIFG, Rojas CAO, Carrasco AGM. Impact of mini-driver genes in the prognosis and tumor features of colorectal cancer samples: a novel perspective to support current biomarkers. PeerJ. 2023;11:11. PubMed PMC

Kumar D, Hassan MK, Pattnaik N, Mohapatra N, Dixit M. Reduced expression of IQGAP2 and higher expression of IQGAP3 correlates with poor prognosis in cancers. PLoS One. 2017;12:e0186977. PubMed PMC

Foda AARM, El-Hawary AK, Elnaghi K, Eldehna WM, Enan ET. Role of MEK1 and DIAPH3 expression in colorectal adenoma-carcinoma sequence. Tumour Biol. 2024;46:1–11. PubMed

Huang R, Wu C, Wen J, Yu J, Zhu H, Yu J, et al. DIAPH3 is a prognostic biomarker and inhibit colorectal cancer progression through maintaining EGFR degradation. Cancer Med. 2022;11:4688–702. PubMed PMC