Colorectal cancer

Colorectal cancer starts in the colon or the rectum, and most cases are of a type of tumor called adenocarcinoma, which is cancer of the cells that line the inside tissue of the colon and rectum. It most commonly starts as a growth, or polyp, on the inner lining and if the growth becomes a cancerous tumor, it can grow out of control and spread to other parts of the body. Most colorectal cancers are related to age and lifestyle factors, while a small number of cases are due to underlying genetic disorders. Some common symptoms include blood in the stool, weight loss, and a change in bowel movements. Colorectal cancer is the third most common cancer and the second most common cause of cancer deaths worldwide.

Figure 1. The volcano plot shows the adjusted p-value compared to the difference in average protein expression (NPX) for all proteins in colorectal cancer compared to all other cancers. The lollipop plot shows the top 10 most important proteins resulting from the cancer prediction model with importance scores ranging between 0 to 100.

Pan-cancer protein panel

10 proteins have been selected for identification of colorectal cancer with two proteins (FKBP1B and PRDX5) that are also selected for lung cancer (Table 1). The top protein for colorectal cancer is PRDX5 wich belongs to the Peroxiredoxins, which are antioxidant enzymes involved in biological functions such as differentiation and cell growth. In addition, PRDXs play critical roles in the occurrence and development of cancers (Gao L et al. (2021)) and interestingly, another PRDX enzyme (PRDX6) is also on the top list for colorectal cancer. Many top proteins for colorectal cancer (FKBP1B, PRDX6 and LGALS4) are plasma membrane proteins expressed in the instestine and notably, LGALS4 functions as a tumor suppressor in colorectal cancer (Satelli A et al. (2011)). Despite earlier studies of the protein profile of blood from colorectal cancer patients using the Proximity Extension Assay, including Harlid et al (Harlid S et al. (2021)), Sun et al (Sun X et al. (2022)), Bhardwaj et al (Bhardwaj M et al. (2021)), Chen et al (Chen H et al. (2015)), Thorsen et al (Thorsen SB et al. (2013)) and Mahboob et al (Mahboob S et al. (2015)), there is little overlap between the suggested biomarkers from these studies and thus comparisons are hard to make. However, TFRC and AREG have been identified as being upregulated in colorectal blood in several studies, supporting the inclusion in our model. Similarly, CEA and GDF-15 found to be significantly up by Chen et al (Chen H et al. (2015)) are both elevated in our study, but were not selected by the model. The 10 panel proteins are able to predict patients with colorectal cancer with high specificity and sensitivity.

Cancer Protein Importance p.adjusted NPX fold change
Colorectal cancer PRDX5 81.3 5.9e-38 0.9
Colorectal cancer TFRC 79.4 4.4e-10 0.3
Colorectal cancer PADI4 76.3 1.9e-4 0.3
Colorectal cancer FKBP1B 71.5 1.9e-33 1.5
Colorectal cancer PRDX6 70.8 1.2e-31 0.5
Colorectal cancer LGALS4 63.6 2.5e-11 0.4
Colorectal cancer CCL20 58.6 2.4e-5 0.4
Colorectal cancer SELE 53.5 1.9e-2 0.1
Colorectal cancer LAP3 52.0 3.8e-5 0.2
Colorectal cancer AREG 50.1 7.3e-7 0.4
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