Proteomic Analysis of Saliva Reveals Changes in Proteomic Profiles During Colorectal Cancer in an Iranian Cohort Publisher



Rezasoltani S ; Biabani A ; Siebels B ; Asadzadeh Aghdaei H ; Conrads G ; Schluter H ; Feizabadi M M
Source: Frontiers in Oncology Published:2026

Abstract

Introduction – Colorectal cancer (CRC) is common and associated with poor survival, and early detection is pivotal to improving patient outcomes. Therefore, identifying reliable biomarkers reflecting early-stage tumor development is of major clinical importance. This study aimed to identify salivary proteins with potential as non-invasive biomarkers associated with early-stage CRC. Methods – A total of 104 saliva samples were collected from individuals undergoing CRC screening, including patients diagnosed with CRC stage I and non-cancer controls (NCC), at Taleghani Hospital, Tehran, Iran, in this case–control study. A quantitative label-free proteomics approach was applied to determine global proteome differences between CRC patients and NCCs and to identify proteins with altered abundance. Proteins were extracted from saliva samples, digested with trypsin, and peptides were analyzed using LC–MS/MS on an Orbitrap Fusion mass spectrometer. Results – A total of 2, 456 salivary proteins were identified, of which 181 showed significantly different abundance between CRC patients and NCCs. Unsupervised clustering demonstrated partial separation of groups with influence from demographic variables. Members of the small proline-rich protein (SPRR) family emerged as consistent core markers distinguishing CRC from NCCs, while additional immune- and metabolism-associated proteins contributed to group differentiation. Demographic subgroup analyses, including age-, sex-, and smoking-stratified comparisons, revealed subgroup-associated differences in protein abundance patterns; however, several CRC-associated alterations remained detectable across subgroups, including middle-aged individuals. Gene set enrichment analysis indicated suppression of cytoskeletal and epithelial structural pathways alongside enrichment of protease regulatory pathways. Ingenuity Pathway Analysis identified an interconnected immune–metabolic network characterized by inflammatory signaling and oxidative stress–related processes. These alterations indicate immune-related and metabolic signaling changes associated with CRC. Discussion – This study supports salivary proteomics as a non-invasive approach for early CRC detection, and the observed proteomic signatures may reflect systemic tumor–immune interactions associated with CRC. Data are available via ProteomeXchange with identifier PXD078610. Copyright © 2026 Rezasoltani, Biabani, Siebels, Asadzadeh Aghdaei, Conrads, Schluter and Feizabadi.