Olink Profiling of Intestinal Tissue Identifies Novel Biomarkers For Colorectal Cancer - first study

Sep 23, 2026

Uploaded by Eliana

Comprehensive protein profiling in intestinal tissues clarifies colorectal cancer (CRC) pathogenesis by mapping oncology-related protein changes across tumor, paired para-carcinoma, and remote normal tissues. Using Olink proteomics, 92 proteins were quantified in 52 CRC patients. Normal tissues closely matched para-carcinoma profiles but differed from tumors. Among 68 differentially expressed proteins, WISP-1, ESM-1, and TFPI-2 showed the strongest alterations, with plasma membrane enrichment and PI3K-AKT pathway signaling implicated. TFPI-2 protein levels were elevated in tumors by Olink and ELISA, highlighting biomarker and therapeutic opportunities.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Introduction

Disease burden and risk factors

Protein roles and proteomic approaches

Olink technology and rationale

This article is licensed under CC-BY-NC-ND 4.0 [pubs.acs.org/jpr](pubs.acs.org/jpr) Article Olink Profiling of Intestinal Tissue Identifies Novel Biomarkers For Colorectal Cancer Chong Xiao, Hao Wu, Jing Long, Fengming You, and Xueke Li* Cite This: J. Proteome Res. 2025, 24, 599−611 Read Online | | | | | | | | --- | --- | --- | --- | --- | --- | | ACCESS | Metrics & More | | Article Recommendations | | *sı Supporting Information | ABSTRACT: Comprehensive protein profiling in intestinal tissues provides detailed information about the pathogenesis of colorectal cancer (CRC). This study quantified the expression levels of 92 oncology-related proteins in tumors, paired para-carcinoma tissues, and remote normal tissues from a cohort of 52 CRC patients utilizing the Olink technology. The proteomic profile of normal tissues closely resembled that of paracarcinoma tissues while distinctly differing from that of tumors. Among the 68 differentially expressed proteins (DEPs) identified between the tumor and normal tissues, WISP-1, ESM-1, and TFPI-2 showed the most pronounced alterations and exhibited relatively strong correlations. These markers also presented the highest AUC values for distinguishing between tissue types. Bioinformatic analysis of the DEPs revealed that the plasma membrane and the PI3K-AKT signaling pathway were among the most enriched GO terms and KEGG pathways. Furthermore, although TFPI-2 is typically recognized as a tumor suppressor, both Olink and enzyme linked immunosorbent assay (ELISA) analyses have demonstrated that its expression is significantly elevated in tumors compared with paired normal tissues. To the best of our knowledge, this is the first study to profile the proteome of intestinal tissue using the Olink technology. This work offers valuable insights into potential biomarkers and therapeutic targets for CRC, complementing the Olink profiling of circulating proteins. KEYWORDS: colorectal cancer, Olink proteomics, tissue, WISP-1, TFPI-2 ■ INTRODUCTION Colorectal cancer (CRC) ranks as the third most prevalent cancer and the second leading cause of cancer-related deaths.1 Projections indicate that by 2040, the incidence of CRC will rise to 3.2 million new diagnoses and 1.6 million fatalities.2 CRC is a multifactorial disease influenced by various factors, including age, diet, smoking, alcohol consumption, and genetic predisposition. Studies have shown that damage to the colorectal mucosa caused by tobacco carcinogens,3 along with intestinal oxidative and nonoxidative metabolism induced by alcohol,4 contribute to the initiation and progression of CRC. Furthermore, poor dietary habits, such as a Westernstyle diet, also contribute to the carcinogenesis of CRC, mainly by inducing the local chronic inflammation and the microbiota dysregulation of the gut.5−7 These risk factors facilitate the malignant transformation of normal mucosa by accumulating alterations related to metabolism and immunity, ultimately leading to the development of CRC. Therefore, investigating the variations in normal mucosa and cancerous tissue is crucial for elucidating the complex mechanisms of CRC. Proteins are central to biological functions and are usually perturbed under pathological conditions. Essential proteins, including the wingless-type MMTV integration site family (WNT), phosphatidylinositol 3-kinase (PI3K), mitogen- activated protein kinase (MAPK), and tumor protein 53 (TP53), contribute to transforming normal mucosa into adenocarcinoma, primarily by influencing cell proliferation, autophagy, apoptosis, and cell differentiation. 8−10 Mass spectrometry-based proteomic analysis has been extensively utilized for the quantitative measurement of protein species and expression levels. For instance, a thorough proteomic investigation of paired tumors and normal tissues has identified novel therapeutic targets for colon cancer.11 Recently, Olinkproteomics has emerged as an effective approach f

FAQs

What tissues and patient cohort were used for the Olink proteomics analysis in CRC?

The study quantified proteins in tumors, paired para-carcinoma tissues, and remote normal tissues from a cohort of 52 CRC patients.

Which differentially expressed proteins showed the most pronounced changes?

WISP-1, ESM-1, and TFPI-2 displayed the most pronounced alterations among the 68 differentially expressed proteins.

What biological pathways were enriched based on bioinformatic analysis?

Bioinformatic analysis indicated enrichment of plasma membrane components and the PI3K-AKT signaling pathway among top GO terms and KEGG pathways.

Sep 23, 2026

Uploaded by Eliana