Several Endometriosis, Preeclampsia Biomarker Candidates Studied, But More Research Needed

Several Endometriosis, Preeclampsia Biomarker Candidates Studied, But More Research Needed

A new review study discussed the evidence supporting several potential biomarkers for the diagnosis of endometriosis and preeclampsia (a pregnancy complication). However, more studies are needed for their clinical validation, according to researchers.

Their study, “Biomarkers for diagnosis of pre-eclampsia and endometriosis,” appeared in the journal Biomarkers in Medicine.

Although several biomarkers of endometriosis and preeclampsia — which affects 2% to 10% of pregnant women and is characterized by high blood pressure and organ damage, mostly in the liver and kidneys — have been proposed, none has been approved to date. This is an unmet need, as both conditions are associated with severe complications.


CA-125- glycoprotein antigen has been associated with the severity and diagnosis of endometriosis and was able to reliably diagnose the disease when assessed with the hormone prolactin.

Follistatin, Zn-alpha-2-glycoprotein, and glycodelin are other glycoproteins proposed as endometriosis biomarkers.

As in preeclampsia, cytokines may also help diagnose endometriosis. Increased levels of IL-4, IL-8 and TNF-alpha have been shown in endometriosis patients. Also, elevated levels of C-reactive protein, an indicator of inflammation, and copeptin have also been seen in these women.

Screening miRNAs may also be useful in endometriosis, as both increases and decreases of specific miRNAs have been reported in these patients. Specific gene variants may also be biomarkers for this disorder.

Oxidative stress-related superoxide dismutase (an enzyme that breaks down the toxic superoxide radical), HDL, LDL, and total cholesterol, as well as triglycerides and vitamin E, may be efficient tools to monitor disease progression. Proteins protecting against oxidative stress — HSPB1 — or involved in innate immunity (CRISP-3 and Pglyrp1) may also help.

Changed levels of proteins involved in cell adhesion and invasion ability — soluble CAM-1, MMP-2, and MMP-9 — have been shown in women with endometriosis. This disorder may also be detected by assessing levels of several autoantibodies, which target the body’s own tissues.

Increased levels of molecules involved in angiogenesis, such as sFlt-1, VEGF and hepatocyte growth factor, have been shown in endometriosos patients.

Metabolites — studied in large-scale studies in a field called metabolomics — may also be useful in endometriosis. Examples of promising candidates include stearic acid, phosphatidylcholines, sphingomyelins (types of lipids, or fat), lactate, glucose, L-alanine, L-leucine, and L-lysine.


The researchers discussed several biomarkers associated with preeclampsia, specifically soluble Flt-1 (sFlt-1), an antiangiogenic form (meaning it opposes the formation of new blood vessels) of the vascular endothelial growth factor (VEGF) receptor-1.

Higher levels of VEGF, the sFlt-1 protein and messenger RNA (mRNA, which contains the information to generate proteins) have been reported in women with preeclampsia.

Soluble endoglin (sEng), a glycoprotein (a protein with a sugar group attached) found outside cells that block endothelial cell proliferation is typically detected after the onset of preeclampsia symptoms and also correlates with the severity of preeclampsia.

Levels of the protein PP13 — involved in arterial remodeling and the formation of the placenta — are reduced in women with preeclampsia, compared to those with normal pregnancies.

Compared to sFlt-1 and other markers, placental growth factor (PIGF) was reported as the best predictor for preeclampsia. An sFlt-1/PIGF ratio has been proposed as a reliable preeclampsia biomarker during the second trimester of pregnancy.

Levels of the protein PAPP-A, which regulates fetal growth, showed a marked decrease during early-onset preeclampsia. A protein called NGAL — with reported higher levels in cancer, cardiovascular disorders, and inflammation — showed increased activity during the second trimester of pregnancy in women with preeclampsia.

Insulin resistance, which is increased in the second and third trimesters, is also associated with this disorder. The level of human placental lactogen, the hormone underlying insulin resistance during pregnancy, is reduced in preeclampsia.

Two other glycoproteins, inhibin A and activin A, show a pronounced increase in women with preeclampsia compared to normal pregnancy.

The protein copeptin has been proposed as an indicator of preeclampsia during first one and a half months of pregnancy. Polymorphisms (gene variations) in the ApoE gene have also been linked to this condition.

Other potential biomarkers for preeclampsia include specific mRNAs and micro RNAs (miRNAs, tiny RNA molecules that regulate gene expression).

Lipid profile, vitamin B12, folic acid, inflammatory markers such as the cytokines interleukin (IL) 1beta, IL-6, and IL10, and oxidative stress indicators such as vitamin C are also potential ways to help diagnose preeclampsia.

“[Despite] promising results obtained through these emerging new biomarkers, extensive clinical research is still needed for validation,” the research team from Pakistan and China wrote.

“[The] scientific community must explore the challenges hindering the validation of candidate biomarkers for endometriosis [and] for preeclampsia,” they added.