IntroductionColorectal cancer (CRC) is one of the most prevalent malignancies and contributes to significant cancer-related deaths worldwide. Despite commonly asymptomatic with 5 year survival rate of 90% at the early stage of disease, extremely low survival rate was reported for late stage diagnosis with metastasis. Therefore, there is an immense urgency for reliable biomarkers to aid in the early diagnosis of CRC and to assist in prognostic stratification. Interrogation on the serum proteome and site-specific secretome may provide an accurate mapping of the circulating and secreted proteins, respectively. Thus, we aim to identify potential protein markers present in human serum, faecal extracts and CRC cells, and to determine its role in CRC.Material and methodsQuantitative proteomics was performed using SWATH-MS analysis on human serum and faecal extracts representing 4 stages of CRC and healthy control. Immuno Blot was conducted to confirm the expression of target proteins in the cell line model for cell manipulation study. Transduction of lentiviral fully sequenced human open reading frames (ORFs) construct into HT29 was carried out with 25 µg/ml Blasticidin S selection for exogenous gene overexpression study. Cell-based assays were performed to evaluate the functional activities and RqPCR for determining the signalling pathway activity.Results and discussionsWe have identified significant upregulation of LRG1 in the sera of CRC patients, particularly in the advanced stage of cancer. The endogenous expression of LRG1 in the CRC cells increased with the advancing stage. Overexpression of LRG1 in HT29 increased cell proliferation by activation of Ki67 mRNA (p<0.01) and cell migration via ZEB1 (p<0.05). The level of TGF-β mRNA was also increased with overexpression of LRG1 (p<0.05).ConclusionIn conclusion, LRG1 is a promising marker for CRC and its overexpression may pose higher risk of metastasis via collective proliferation, migration and invasion possibly through the regulation of TGF-β pathway.