Unveiling The Significance: What Are Tumour Markers?
Published on: August 5, 2024
Unveiling The Significance What Are Tumour Markers
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Elena Paspel

Master of Science in Engineering (Digital Health) - <a href="https://taltech.ee/en/" rel="nofollow">Tallinn University of Technology, Estonia</a>

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Regina Lopes

Junior Editor, Centre of Excellence, Health and Social Care, The Open University

Introduction

Tumour markers are like little biochemical detectives that help diagnose and treat cancer. The most common are carcinoembryonic antigens (CEA) for colorectal and gastric cancers, Alpha-Fetoprotein (AFP) for liver cancer and Hepatocellular carcinomas (HCC), and Cancer Antigen 125 (CA-125) for ovarian cancer. The use of liquid biopsy has been a huge step forward in diagnosis as a non-invasive way to detect tumour markers and understand how cancer behaves. Improvements to this technique are being made all the time increasing sensitivity and precision.

Tumour indicators will be found in your blood, saliva or urine. They indicate that something is not quite right. Tumour markers act as a specialised surveillance system within the body to alert medical professionals to the presence and progression of cancer.

Why do tumour markers matter?

Tumour markers are essential indicators for cancer diagnosis, prognosis, and monitoring. They could potentially facilitate the early detection of cancer, which may greatly enhance the effectiveness of treatment.8 

Early detection might significantly boost your chances of a full recovery. It is also important to note that liquid biopsy, a non-invasive method, is gradually changing the game by making tumour marker identification simpler than it was in the past.2

Common tumour markers

Here are the most common ones and the cancers they are associated with:

CA 125: ovarian cancer marker

Cancer antigen 125 (CA 125) is recognised for its role in detecting ovarian cancer. This marker, found on cell surfaces and in the blood of women with ovarian cancer, acts as a trace of the disease.3

How is this marker used? A straightforward blood test can reveal elevated CA 125 levels, which might suggest the presence of ovarian cancer. However, CA 125 does not function in isolation.  With (Human Epididymis Protein 4) CA 125 is not just any old marker - it's a crucial part of something called the Risk of Ovarian Malignancy Algorithm (ROMA). This method boosts diagnostic accuracy and helps categorise patients as low or high risk for ovarian cancer.  CA 125 is not just for diagnosis,  it can also indicate  how ovarian cancer patients are responding to treatment.3

CA 125 is important for tracking how patients with ovarian cancer respond to  treatment. A decrease in CA 125 levels post-treatment usually signals a positive treatment response, whereas persistently high or increasing levels might indicate ineffective treatment or disease recurrence.3

CA 125 has some limitations. It may not be elevated in the early stages of ovarian cancer, which is why it is often used alongside other biomarkers and diagnostic techniques to achieve a more accurate diagnosis and effective management of the disease.

Prostate-specific antigen (PSA)

Prostate-specific antigen (PSA),  is produced by cells of the prostate gland.  It is important for the detection, tracking, and evaluation of prostate cancer. The function of PSA as a tumour marker is fundamental in the clinical management of prostate cancer.5

Monitoring PSA levels allows healthcare professionals to gather crucial information that may aid in the early detection and diagnosis of prostate cancer. These insights are essential for ongoing patient monitoring, which might improve outcomes and therapy for those suffering from this condition.5

Alpha-fetoprotein (AFP): the liver cancer marker

AFP, or alpha-fetoprotein, is a marker for Hepatocellular carcinoma (HCC). For over sixty years, AFP has helped screen, diagnose, predict, and assess liver cancer treatment. It is an important factor  in clinical settings and guiding decisions like liver transplantation.9 However, there is a limitation: about 30% of liver cancer patients do not show high AFP levels. This makes early diagnosis and management challenging. These patients tend to have smaller tumours, fewer recurrences, and better liver function.9 Currently,  scientists are looking into other markers and diagnostic methods.

Carcinoembryonic antigen (CEA)

Carcinoembryonic antigen (CEA) is important for tracking the efficacy of treatment and identifying recurrence in individuals with colorectal cancer. Higher values of CEA might be a sign that cancerous tumours are present in the colorectal area.1 Use of CEA goes beyond colorectal cancer; it has an extensive importance in oncology and it is frequently used as a biomarker in gastric cancer.6 Its levels might also be increased in benign diseases and different types of cancer.  

CA19-9: an indicator for gastric cancer

CA19-9 (carbohydrate antigen 19-9) is a marker for gastric cancer. In the battle against stomach cancer; molecular and circulating biomarkers are essential because, by enabling early detection, they may improve patient survival and quality of life.6 Increased levels of CA19-9 levels may indicate an advanced stage of the disease and suggest a poor prognosis. Therefore, it is a helpful marker for assessing the effectiveness of treatment and the advancement of the illness in patients with stomach cancer.6

Circulating tumour cells (CTCs)

Circulating tumour cells (CTCs) are messengers within the bloodstream, revealing potential cancer spread. These cells detach from the primary tumour and circulate through the blood, covertly transporting information on cancer progression.7

Since their discovery, CTCs have been the subject of in-depth investigation. According to observations, CTCs may be in the circulation before medical scans may identify visible indicators of cancer spread or recurrence. This might facilitate an early diagnosis and offer information on how the illness develops.10,7

How tumour markers detect cancer

Tumour markers might be found on the surface of cells, inside cells, or as various molecules such as hormones, enzymes, or even genetic material.4 Each marker helps piece together the complex puzzle of diagnosing cancer.

Gene alterations in cancer cells have a cascading impact that modifies the activity of genes within and outside of the cells.4

Diagnostic method: liquid biopsy

In medical diagnostics, methods like liquid biopsy serve as this control panel. They collect and analyse the signals of tumour markers from blood, urine, or other body fluids to assess the presence of cancer. It acts as a detection tool but without the need for surgery. The signs of cancer detected via the liquid biopsy could be actual cancer cells shed by a tumour or tiny bits of tumour DNA floating in the bloodstream.

While blood is a common sample for measuring tumour markers, they can also be found in urine, tissues, or other body fluids. Liquid biopsy lets us find and study these markers, including circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and other significant molecules like proteins and RNAs.2 When cancer is present, these markers are found in greater numbers and are used alongside other tests to confirm a cancer diagnosis.5

The usefulness of liquid biopsy extends beyond detection. It also provides an  insight into a  tumour's response   to treatment and tracks its progression during and after therapy. This includes spotting any signs that the cancer might be reoccurring.1

The limitations of tumour markers

It is widely recognised in medical circles that these markers have limitations that cannot be overlooked.4

Specificity and sensitivity

When it comes to accuracy, tumour markers are not always specific. Their levels might rise not just because of cancer but due to benign conditions or various cancers. It can be quite difficult to identify these markers at low levels, especially in the early stages of the illness.8

Patient impact: the emotional and financial terrain

Dealing with cancer challenges patients not just physically, but emotionally and financially as well. The journey can be incredibly draining, stretching both emotional and financial resources thin.

Emotional impact

There is a great deal of emotional stress particularly when diagnostic testing produce unclear outcomes. Consider the anxiety of being incorrectly told you might have cancer, or the risks of undetected cancer due to false negatives. The former scenario can cause immense stress and fear for patients and their families, while the latter might delay necessary treatment, allowing the disease to progress.

Financial impact

The financial burden of cancer is also profound. Unclear initial test results often necessitate repeated tests, additional doctor visits, and sometimes more complex procedures, which can rapidly increase expenses. A family's financial burden is further increased by indirect costs like lost wages, travel expenditures for doctor's visits, and expenses for child or elder care.

The future of tumour markers

The field of oncology also sees continuous improvement in tumour markers and diagnostic methods. Researchers are developing new biomarkers and refining existing ones to increase their accuracy, specificity, and reliability in detecting and monitoring various types of cancer.

Summary

Tumour markers are biochemical markers that are used for the diagnosis and treatment of cancer.

Well-known markers include:

  • CEA for colorectal and gastric cancers
  • AFP for liver cancer (HCC)
  • CA 125 for ovarian cancer

The introduction of liquid biopsy has transformed the way cancer is diagnosed, being a non-invasive method to detect tumour markers and understand cancer behaviour.

Even while there are still issues with sensitivity and precision, continued advancements are expected  to lead to new approaches and increased accuracy in the fight against cancer.

References

  1. Nagpal M, Singh S, Singh P, Chauhan P, Zaidi MA. Tumor markers: A diagnostic tool. Natl J Maxillofac Surg [Internet]. 2016 [cited 2023 Sep 28];7(1):17–20. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242068/ 
  2. Lone SN, Nisar S, Masoodi T, Singh M, Rizwan A, Hashem S, et al. Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments. Mol Cancer [Internet]. 2022 Mar 18 [cited 2023 Sep 28];21:79. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932066/ 
  3. Dochez V, Caillon H, Vaucel E, Dimet J, Winer N, Ducarme G. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. J Ovarian Res [Internet]. 2019 Mar 27 [cited 2023 Sep 28];12:28. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436208/ 
  4. Sharma S. Tumor markers in clinical practice: General principles and guidelines. Indian J Med Paediatr Oncol [Internet]. 2009 [cited 2023 Sep 28];30(1):1–8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902207/ 
  5. Filella X, Rodríguez-Garcia M, Fernández-Galán E. Clinical usefulness of circulating tumor markers. Clinical Chemistry and Laboratory Medicine (CCLM) [Internet]. 2023 Apr 1 [cited 2023 Sep 28];61(5):895–905. Available from: https://www.degruyter.com/document/doi/10.1515/cclm-2022-1090/html 
  6. Jelski W, Mroczko B. Molecular and circulating biomarkers of gastric cancer. Int J Mol Sci [Internet]. 2022 Jul 8 [cited 2023 Sep 28];23(14):7588. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322632/ 
  7. Lin D, Shen L, Luo M, Zhang K, Li J, Yang Q, et al. Circulating tumour cells: biology and clinical significance. Signal Transduct Target Ther [Internet]. 2021 Nov 22 [cited 2023 Sep 28];6:404. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606574/ 
  8. Kwong GA, Ghosh S, Gamboa L, Patriotis C, Srivastava S, Bhatia SN. Synthetic biomarkers: a twenty-first century path to early cancer detection. Nat Rev Cancer [Internet]. 2021 Oct [cited 2023 Sep 28];21(10):655–68. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8791024/ 
  9. Hu X, Chen R, Wei Q, Xu X. The landscape of alpha fetoprotein in hepatocellular carcinoma: where are we? Int J Biol Sci [Internet]. 2022 Jan 1 [cited 2023 Sep 28];18(2):536–51. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8741863/
  10. Zhen DZ, Li YS, Su CY, Cheng X, Zhou SJ, Han Y, et al. The expression level of epithelial cell adhesion molecule (Epcam) of circulating tumor cells (Ctcs) of patients with NSCLC as an early indicator to monitor the effects of postoperative adjuvant chemotherapy. Translational Cancer Research [Internet]. 2021 Jul [cited 2023 Sep 29];10(7). Available from: https://tcr.amegroups.org/article/view/54414 
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Elena Paspel

Master of Science in Engineering (Digital Health) - Tallinn University of Technology, Estonia

Bachelor of Laws - LLB (Hons), London Metropolitan University, UK

An experienced professional with a diverse background spanning law, pricing, and eHealth/Digital Health. Proficient in copywriting, medical terminology, healthcare interoperability standards, and MedTech regulations. A strong foundation in scientific research methodologies and user experience research supports the creation of compelling content for the biopharmaceutical, CROs, medical technology, and eHealth sectors.

Proven expertise in driving product vision, synthesizing complex information, and delivering user-centric solutions. Adept at streamlining workflows and processes, and drafting documentation and SOPs. Always open to collaborations and eager to connect with like-minded professionals.

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