Studying Serum of Protein Biomarkers for Colorectal Cancer Detection Using LC-MS/MS

A recent study published in the World Journal of Gastrointestinal Oncology (1) used liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS) to identify serum protein biomarkers for the early screening of advanced adenoma (AA) and colorectal cancer (CRC), which is the third most common cancer in the world and the second leading cause of cancer-related death [2]).

The study states that the incidence of early-onset CRC has been increasing in many countries over the past few decades. Some of the factors that are likely contributors to this increase include change in diets, an increase in obesity, and lack of physical activity. The majority of these cancer cases develop from colorectal adenomas, particularly advanced adenomas (AAs), which are defined as having any of the following features: a size equal to or greater than 10 mm, high-grade dysplasia (a term used to describe the presence of abnormal cells within a tissue or organ [3]), or a ≥ 25% villous component (defined as type of polyp that grows primarily in the colon and other places in the gastrointestinal tract [4]). According to previous studies, the five-year survival rate of patients with localized CRC after curative surgery is approximately 90%, but it decreases to approximately 65% in patients with regional lymph node metastasis (5). Therefore, early diagnosis and treatment of CRC are therefore key measures in the improvement of patient prognosis.

Researchers at the China-Japan Friendship Hospital in Beijing, China, collected 43 serum samples from 8 normal controls (NCs), 19 AA patients and 16 CRC patients at the hospital between June and August of 2023. Quantitative proteomic analysis was performed using LC-MS/MS, and data independent acquisition, and differentially expressed proteins (DEPs) with P-values < 0.05 and absolute fold changes > 1.5 were screened out, followed by bioinformatics analysis. more than 2000 proteins were identified, a number the authors claim to be much higher than in previous studies of this type.

The study revealed the serum proteomic profiles of AA and CRC patients, and clarified the functions of DEPs, and identified seven proteins (DIAPH1, VASP, RAB11B, LBP, SAR1A, TUBGCP5, and DOK3) which the authors of the study believe indicate their ability to be serum screening biomarkers for AA and CRC, with two of these proteins, lipopolysaccharide binding protein (LBP) and vasodilator-stimulated phosphoprotein (VASP), possibly more promising for the early screening and detection of colorectal tumors.

However, the authors admit that there are some limitations to their research. As a single center study, only a limited number of patients were included. Therefore, the possibility of selection bias cannot be ruled out, illustrating the need to validate the findings in a larger sample size in the future. In these subsequent studies, the authors believe it will be possible to further increase the nonadvanced adenoma subgroup and follow up on their recurrence and prognosis outcomes to observe the impact of characteristic proteins on disease progression. Also, the lack of complete genomic and transcriptomic data hinders the integrated study of gene-mRNA-protein interactions. Further analysis of the core genes through the protein-protein interaction (PPI) network will be necessary. Additionally, the protein mechanisms need to be further investigated and validated in CRC tissues. While omics technologies have greatly advanced cancer biomarker research, the authors state that more research still needs to be done before these technologies can be clinically applied.

Colorectal cancer awareness medical concept. Concept of cancer treatment and prevention, 3D illustration. © Dr_microbe - stock.adobe.com

References

1. Tan, C.; Qin, G.; Wang, Q. Q.; Li, K. M.; Zhou, Y. C.; Yao, S. K. Comprehensive Serum Proteomics Profiles and Potential Protein Biomarkers for the Early Detection of Advanced Adenoma and Colorectal Cancer. World J. Gastrointest. Oncol. 2024, 16 (7), 2971-2987. DOI: 10.4251/wjgo.v16.i7.2971

2. Sung, H.; Ferlay, J.; Siege, R. L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209-249. DOI: 10.3322/caac.21660

3. Dysplasia definition. National Cancer Institute webpage. (accessed 2024-07-20).

4. Villous adenoma definition. National Cancer Institute webpage. (accessed 2024-07-20).

5. Pfister, D. G.; Benson III, A. B.; Somerfield, M. R. Surveillance Strategies After Curative Treatment of Colorectal Cancer. N. Engl. J. Med. 2004, 350, 2375-2382. DOI: 10.1056/NEJMcp010529