Urine as an emerging liquid biopsy for endometrial cancer biomarker detection

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Urine as an emerging liquid biopsy for endometrial cancer biomarker detection

The problem:

This gynecological awareness month, we focus on endometrial cancer, which affects the lining of the uterus in a women's pelvis. This is the most frequently diagnosed malignancy of the female genital tract and the sixth most common cancer in women globally (1).

Early diagnosis of the cancer type can greatly increase chances of survival; the five-year survival rate is over 90% in early-stage disease but less than 20% in advanced disease stage (2). One of the most common signs that occur in most women with endometrial cancer is postmenopausal bleeding (PMB).

endometrial cancer_figure 1 facts.jpg

Current methods of detection to help rule out malignant disease states, include sequential transvaginal ultrasound scan (TVS), outpatient hysteroscopy and endometrial biopsy; however, these procedures have limitations. TVS lack specificity, while the other methods are invasive, as well as difficult to perform, which can lead to repeat testing. Millions of women who do not have endometrial cancer undergo these invasive tests every year, which can be painful, costly for an individual and an added burden on the healthcare system as whole (3).

Finding a simple, non-invasive test that identifies endometrial cancer effectively could transform the way the disease is detected and improve patient care.

 

Urine as a sample type:

An ideal detection tool for endometrial cancer would be a non-invasive, cost-effective procedure, that would be able to accurately detect early-stage cancer with low false positives or negatives (1).

Urine has shown to be a promising sample type for several types of gynecological cancers including cervical and ovarian cancer (4). As urine is easily accessible, has a low collection cost, as well as allows for repeated sampling non-invasively, the sample type is attractive for biomarker detection for endometrial cancer. Additionally, endometrial cancer is known to shed malignant cells through the cervix into the lower genital tract, allowing it to be released into urine (1).

endometrial cancer_Figure 2_biomarkers V3.jpg

 

Multi-omic technologies empower the search for an ideal endometrial cancer biomarker:

Recent advancements in omics technologies have improved our understanding of the molecular landscape of cancers. Studies are looking into various biomarker candidates for endometrial cancer in urine, including DNA, RNA, proteins and metabolites.

A recent systematic review shows miRNAs are potentially promising endometrial cancer biomarkers (especially miR-205, the miR-200 family and miR-135b, -182, -183 and -223). However, more work needs to be done to validate the diagnostic potential of these miRNAs in larger clinical studies (5).

Protein biomarkers have shown several advantages over RNA, DNA and metabolites for endometrial cancer. The reasons for this are that a large part of the human proteome is detectable in easily accessible biological fluids, and proteins can be easily isolated and quantified using commonly used laboratory tests such as enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. (2)

One study reported that urinary levels of Zinc alpha-2 glycoprotein, alpha-1 acid glycoprotein and CD59 were upregulated in patients with endometrial cancer compared to healthy controls while nebulin was downregulated. (1)

Another study showed that the MCM5 (mini chromosome maintenance 5) protein can be detected in the urine sediments of patients with endometrial cancer in excess compared to those in patients with benign gynecological conditions. In addition, another advantage is that the MCM5 test is an easy-to-perform ELISA test, compatible with general laboratory equipment available in most hospital laboratories (6).

Finally, the study by O’Flynn et al. provided proof-of-principle that endometrial cancer can be detected by cytology in voided urine and non-invasive vaginal samples with high diagnostic accuracy. While this data is very promising, the clinical utility of urogenital cytology for endometrial cancer detection must be confirmed in more studies, especially in women with unexplained PMB undergoing routine diagnostic investigations (3). The aim of the DETECT study is to establish the diagnostic test accuracy of vaginal and urine samples for endometrial cancer detection by cytology in women with PMB (7).

 

Future perspectives:

Given the wide array of biomarkers in urine, the sample type is a promising in endometrial cancer research.

However, for effective clinical applications, standardization of preanalytical conditions for the handling of urine specimens is required. More work needs to be done to better understand if factors such as method of urine collection, urine fractions, and the need for urine preservation can influence biomarker detection for endometrial cancer.

Novosanis' Colli-Pee®, a urine collection device which can be prefilled with a preservative, allows for volumetric collection of different urine volumes. First-void urine has shown potential for biomarker detection for several cancer types.

 

References:

  1. PMID 33224875

  2. PMID: 31623106

  3. PMID: 33574259

  4. https://novosanis.com/blog/urine-way-screen-more-women-gynecological-can...

  5. PMID: 32523655

  6. PMID 33059604

  7. PMID 34321307

 

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