Identification of driving genes of familial adenomatous polyposis by differential gene expression analysis and weighted gene co-expression network analysis

Sep 21, 2026

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Familial adenomatous polyposis (FAP) shows stable or increasing cancerization rates despite screening advances and pharmacological therapies, highlighting the need to clarify disease mechanisms. The study aims to identify genes driving FAP pathogenesis through differential gene expression profiling and weighted gene co-expression network analysis. Immune infiltration patterns were evaluated using TIP, key module genes were integrated with signature genes, and five candidate biomarkers were validated in intratumoral and tumor rim regions using qRT-PCR.

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Technology and Health Care 32 (2024) 1675–1696 1675 DOI 10.3233/THC-230719 IOS Press Identiﬁcation of driving genes of familial adenomatous polyposis by differential gene expression analysis and weighted gene co-expression network analysis Wan-Rong Lina ; 1 , Wei-Qing Liub ; 1 , Xuan-Yu Menga , Xiao-Ting Liua , Zhi-Yong Koua , Wen-Liang Lic and Jun Yanga ;􀀃 a Department of Oncology, The First Afﬁliated Hospital of Kunming Medical University, Kunming, Yunnan, China b Department of Internal Medicine-Oncology, The First Afﬁliated Hospital of Kunming Medical University, Kunming, Yunnan, China c Colorectal Cancer Clinical Research Center, Third Afﬁliated Hospital, Kunming Medical University, Kunming, Yunnan, China Received 1 June 2023 Accepted 7 October 2023 Abstract. BACKGROUND: Despite the advancement of new screening strategies and the advances in pharmacological therapies, the cancerization rates of familial adenomatous polyposis (FAP) are stable and even increased in the last years. Therefore, it necessitates additional research to characterize and understand the underlying mechanisms of FAP. OBJECTIVE: To determine the genes that drive the pathogenesis of familial adenomatous polyposis (FAP) . METHODS: We performed on a cohort (GSE111156) gene proﬁle, which consist of four group of gene expressions (the gene expressions of cancer, adenoma and normal tissue of duodenal cancer from patients with FAP were deﬁned as Case N, Case A and Case C respectively, while that of adenoma tissue from patients with FAP who did not have duodenal cancer was Ctrl A) . Tracking Tumor Immunophenotype (TIP) website was applied to reveal immune inﬁltration proﬁle and signature genes of FAP. We merged the genes of key module (pink and midnight module) with signature genes to obtained the biomarkers related with FAP pathogenesis. The expression of these ﬁve biomarkers in FAP intratumoral region (IT) and tumor rim (TR) was detected with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) . RESULTS: In total, 220, 23 and 63 DEGs were determined in Cases C, A and N, in comparison to Ctrl A. In total, 196 and 10 DEGs were determined in Cases C and A, separately, as compared to Case N. A total of four biomarkers including CCL5, CD3G, CD2 and TLR3 were ﬁnally identiﬁed associated with pink module, while only one biomarker (KLF2) associated with midnight module was identiﬁed. All biomarkers were evidently raised in FAP IT tissues utilizing qRT-PCR. CONCLUSION: We identiﬁed ﬁve potential biomarkers for pathogenesis of FAP to understand the fundamental mechanisms of FAP progression and revealed some probable targets for the diagnosis or treatment of FAP. Keywords: Familial adenomatous polyposis, bioinformatics, driver gene, WGCNA, DEGs 1These authors contributed equally to this work. 􀀃 Corresponding author: Jun Yang, Department of Oncology, The First Afﬁliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China. Tel.: +86 87165324888; E-mail: [yangjun6@kmmu.edu.cn](yangjun6@kmmu.edu.cn). 0928-7329 􀀍c 2024 – The authors. Published by IOS Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC 4 .0) . 1676 W.-R. Lin et al. / Identifying genes related with FAP 1. Introduction Familial adenomatous polyposis (FAP) is an autosomal dominant disorder resulting from mutations in the adenomatous polyposis coli (APC) gene [1,2] . FAP is the most common intestinal polyposis [3], and the most prominent feature is multiple adenomatous polyposis of the digestive tract which frequently leads to obstruction, gastrointestinal bleeding as well as other complications [4] . Polyposis can also develop into colorectal cancer and directly endanger human life and health [5] . Despite the advancement of new screening strategies and the advances in pharmacological therapies, the cancerization rates of FAPare stable and even increased in the last

FAQs

Why is additional research needed for familial adenomatous polyposis (FAP)?

Even with advances in screening strategies and pharmacological therapies, FAP cancerization rates remain stable or increase, requiring deeper mechanistic understanding.

What methods were used to identify candidate FAP driving genes?

The workflow combined differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), immune infiltration profiling using the TIP website, and integration of module genes with signature genes.

Which biomarkers were finally identified as associated with FAP?

Five biomarkers were identified: CCL5, CD3G, CD2, and TLR3 (linked to the pink module) plus KLF2 (linked to the midnight module), all showing elevated expression in FAP tissues by qRT-PCR.

Sep 21, 2026

Uploaded by Eliana