In the field of cancer research, scientists and biologists are constantly seeking innovative approaches to understand the intricate mechanisms underlying tumor development and progression. One such cutting-edge technology that has revolutionized the study of cancer is proteomics. With its ability to comprehensively analyze the complete set of proteins within a biological system, proteomics holds immense potential in unraveling the mysteries of tumors and aiding in the development of targeted therapies.
What can Proteomics offer to Cancer Research?
Identification of biomarkers:
Proteomics plays a pivotal role in identifying potential biomarkers for cancer diagnosis, prognosis, and treatment response prediction. By comparing protein profiles between healthy and cancerous tissues, researchers can identify specific proteins that are overexpressed or underexpressed in tumors. These differentially expressed proteins serve as potential biomarkers that can aid in early detection and personalized treatment strategies for cancer patients.
Unraveling tumor heterogeneity:
Tumors are highly complex and heterogeneous, consisting of distinct populations of cells with different characteristics. Proteomics allows the analysis of individual cells within a tumor, providing insight into the heterogeneity and dynamics of tumor development and helping to understand drug resistance, metastasis and the design of tailored therapies targeting specific cell populations.
Elucidating signaling pathways:
Aberrant signaling pathways are often responsible for the uncontrolled growth and survival of cancer cells. Proteomics enables the identification and characterization of key proteins involved in these signaling cascades. By mapping out the intricate network of protein interactions, proteomics helps researchers identify potential therapeutic targets for intervention and develop novel drugs that can disrupt tumor-promoting pathways.
Studying protein post-translational modifications:
Post-translational modifications (PTMs) play a critical role in regulating protein function and cellular processes. Proteomics techniques can identify and quantify PTMs, such as phosphorylation, acetylation, and glycosylation, within cancer cells. This knowledge aids in understanding how PTMs contribute to tumor development, progression, and response to treatment, opening up new avenues for targeted therapies.
Workflow of the proteomics investigation (Kwon et al., 2021).
Advances in Proteomics for Cancer Research
Protein profiling applied to prostate cancer research
Prostate cancer is a malignant tumor that occurs in the epithelial cells of the prostate gland and is the second most commonly diagnosed malignancy worldwide. Ahram et al. used two-dimensional gel electrophoresis to analyze paired cellular protein profiles of normal and tumor cells in human prostate specimens, identifying changes in 40 tumor-specific proteins. Although the significance of these specific alterations is unclear, they directly imply efforts in identifying new clinical diagnostic and therapeutic targets for prostate cancer. On the other hand, Sanja Kiprijanovska et al. chose urine samples from clinical patients to study prostate cancer. By comparing 45 identified proteins from 2D PAGE/MS with proteins identified in normal urine, they found that 34 of these proteins were also present in normal urine, while the remaining 11 proteins had not been reported. Additionally, they discovered four proteins (antithrombin III, transmembrane and immunoglobulin protein, tumor protein D52, and inosine monophosphate dehydrogenase) that were associated with different types of cancer as well as bodily injury and abnormalities. Furthermore, in the molecular and cellular functional classification, they found that three of these proteins were related to cell survival, proliferation, and apoptosis. The findings of this study provide some clues to understand the molecular basis of prostate cancer.
Proteins that were unchanged (black text), upregulated in tumors (red text), or downregulated in tumors (green text) (Ahram et al., 2002).
Proteomics applied to gastric cancer research
Gastric cancer is one of the common cancers in Asia and exhibits inherent resistance to many anticancer drugs. Therefore, numerous studies have attempted to identify key biomarkers, and proteomics technology provides essential tools for discovering and identifying disease-related biomarkers.
JinWoo Ryu utilized two-dimensional gel electrophoresis of gastric cancer tissues and identified 140 protein spots. Among the identified proteins, seven were found to be overexpressed and seven were underexpressed in gastric cancer tissues. These findings hold the potential to correlate with clinical data and determine useful biomarkers.
Zhigang Bai et al. analyzed paired protein expression patterns in gastric cancer tissues and normal gastric mucosa from eight gastric cancer patients. They performed comparative proteomic analysis using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). They discovered 26 upregulated proteins and six downregulated proteins in tumor tissues, with nine proteins involved in apoptosis. Additionally, they identified for the first time that changes in the phosphorylation activity of PPIA play a crucial role in the occurrence and development of human gastric cancer. They proposed ENO1, GRP78, GRP94, PPIA, PRDX1, and PTEN as potential gastric cancer biomarkers.
Proteomics applied to liver cancer research
Liver cancer is the most common cancer worldwide, with a particularly high incidence, with approximately 82% of cases occurring in developing countries. Globally, liver cancer ranks sixth in cancer incidence and third in cancer-related mortality.
Hindupur et al. conducted proteomics research on 12 liver tumors in a mouse model of liver cancer and found a significant upregulation of histidine phosphorylation in overall proteins in liver tumors. They also observed that sustained liver expression of LHPP in a mouse model of hepatocellular carcinoma (HCC) alleviated tumor burden and prevented liver dysfunction. The low expression of LHPP was associated with increased tumor severity and decreased overall survival, indicating LHPP as a protein histidine phosphatase and tumor suppressor, suggesting the involvement of histidine regulation.
In a study by Pengyuan Yang, serum samples from 27 liver cancer patients were compared. Using two-dimensional gel electrophoresis and mass spectrometry techniques, they identified five significantly differentially expressed proteins.
Proteomics applied to lung cancer research
Lung cancer is a highly lethal cancer with a 15% survival rate, making it the lowest among all cancers. Grasso CS applied mass spectrometry technology and identified a total of 51 differentially expressed proteins, with 29 upregulated proteins and 22 downregulated proteins. The downregulated proteins were mainly involved in the regulation of nutrient or drug metabolism. On the other hand, many proteins induced by TGF-alpha, such as heat shock protein 27 and glutamine transaminase, are involved in regulating cell migration, adhesion, and invasion, playing a role in cancer development.
ATCHARARUBPORN et al. performed two-dimensional gel electrophoresis on lung cancer cells and identified proteins using electrospray ionization mass spectrometry. They found that heterogeneous nuclear ribonucleoprotein A1, nuclear factor KAP1, transketolase, and cytokeratin 18 were expressed exclusively in lung cancer cells. Additionally, in lung cancer cells, phosphoprotein enriched in astrocytes 60 (PEA-15) exhibited high expression. PEA-15 plays an important role in protein-protein interactions and protein conformation. Therefore, its overexpression in cells may lead to abnormal protein conformation, triggering early-stage cancer. Thus, these proteins have the potential to serve as biomarkers for early detection of lung cancer.
GO analysis of the specific proteins of adenocarcinoma and squamous carcinoma cell lines: biological process and molecular function (Korrodi et al., 2016).
References
- Kwon, Yang Woo, et al. "Application of proteomics in cancer: Recent trends and approaches for biomarkers discovery." Frontiers in Medicine (2021): 1644.
- Ahram, Mamoun, et al. "Proteomic analysis of human prostate cancer." Molecular Carcinogenesis: Published in cooperation with the University of Texas MD Anderson Cancer Center 33.1 (2002): 9-15.
- Kiprijanovska, Sanja, et al. "Mapping and identification of the urine proteome of prostate cancer patients by 2D PAGE/MS." International journal of proteomics 2014 (2014).
- Indovina, Paola, et al. "Lung cancer proteomics: recent advances in biomarker discovery." International journal of proteomics 2011 (2011).
- Korrodi-Gregorio, Luis, et al. "From proteomic analysis to potential therapeutic targets: Functional profile of two lung cancer cell lines, A549 and SW900, widely studied in pre-clinical research." PLoS One 11.11 (2016): e0165973.
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