Echinoccocosis is a parasitic disease caused by a cestode belonging to the genus Echinococcus. The most important species for medical purposes are E. granulosus (cystic echinococcosis) and E. multilocularis (alveolar echinococosis). The liver is the most commonly invaded organ (the liver and the lungs represent more than 90% of reported cases). Pathological symptoms such as abdominal pain and/or jaundice are caused by the pressure the enlarged cyst exerts on the liver tissue. There is additionally a palpable mass in the hepatic area 1 . Similar symptoms are registered in patients with liver cancer. Moreover, echinococcosis and liver cancer have a long asymptotic occurrence. Cystic echinococcosis is usually easy to diagnose using an ultrasound image. It is, however, occasionally difficult to distinguish it from other liver tumours. In these cases, other diagnostic tools, such as serological tests, are used. False positive or false negative reactions, however, may still occur 2 . Moreover, echinococcosis is sometimes not considered during medical diagnosis due to the incidence rates of the two diseases. An erroneous diagnosis of a cyst as being a cancer is associated with the risk of its being damaged during surgery. This can result in anaphylactic shock. Proper cancer markers should therefore be able to distinguish between the cancer and the parasitic cyst.

An increasing number of publications are suggesting that galectin-3 (Gal-3) and soluble cadherin fragments, such as E-cadherin (sE-CAD) and N-cadherin (sN-CAD), may be considered as cancer markers. Although the concentration of proper cancer markers should not only distinguish between healthy and cancerous subjects, but also between cancerous subjects and those suffering from other tumour progression diseases such as echinococcosis, there are no data concerning sE-CAD, sN-CAD and Gal-3 levels in the plasma of echinococcosis patients. This disease may sometimes be misdiagnosed as cancer, which can result in patient death.

The aim of the present study was to observe whether echinococcosis affects the concentration of soluble sN-CAD, sE-CAD fragments and Gal-3 in plasma and to determine which of them are suitable for further research as reliable liver cancer markers.

Galectin-3 is reported to be overexpressed in a variety of neoplastic cells and is suggested to be involved in tumour metastasis by, e.g. enhancing adhesion between tumour cells and extracellular matrix, promoting embolization. However, no generalized conclusion on the role of Gal-3 in cancer has yet been established. The lectin is not only produced and secreted into the plasma by tumour tissues, but also by peritumoural inflammatory cells and stromal cells.

Elevated Gal-3 levels in the serum/plasma have been reported in some cancers, e.g., metastatic breast and gastrointestinal cancer. However, decreased levels of this lectin have been observed in metastatic breast, endometrial and ovary carcinomas, while the levels in Non-Hodgkin's lymphoma and melanoma 4 have not been observed to change. Elevated levels of circulating Gal-3 have not only been observed in cancers, but also in chronic inflammations, e.g. inflammatory bowel disease 5 , obesity, type 2 diabetes 6 , and heart failure 7 8 . The present studies showed that a higher circulating Gal-3 concentration was observed in liver cancer (NS) and echinococcosis patients than in the healthy control group. The results concerning the cancerous patients, even if not significant, seem to be consistent with the results mentioned above 4 as well as with those reported by Matsuda et al. 9 , who observed a higher level of the circulating lectin in liver cancer than in the control group and subjects with chronic liver disease. However, the present report would seem to be the first to compare the levels of Gal-3 in the plasma of cancer patients, echinoccosis patients and healthy volunteers. The highest level observed in echinococcosis could be the result of inflammation related to parasite invasion. Nevertheless, liver cancer is also associated with inflammation and exhibited similar CRP levels to, and higher leukocyte levels than, echinococcosis. Factors other than the inflammation that occurs in echinococcosis might therefore influence the Gal-3 level in the plasma.

sE-cadherin is a form, cleaved from E-cadherin by proteases such as MMP-3, MMP-7 10 , plasmin 11 , ADAM10 12 , ADAM15 13 , whereas sN-CAD is cleaved by ADAM10 14 , MT1-MMP 15 , MT5-MMP 16 , MMP-9, MMP-12 17 , and Presenilin 1 18 . The induction/upregulation of various MMPs (e.g. MMP-2, MMP-3, MMP-7 and/or MMP-9) has been detected in tumourous liver tissues obtained from, e.g. hepatocellular carcinoma (HCC) patients, whereas the expression of plasminogen activators appears to be largely confined to stromal and inflammatory cells. Inflammation also enhances the expression of MMPs, e.g. in endothelial cells, lymphocytes and macrophages. Furthermore, the expression of certain MMPs and plasminogen activators is also increased in liver cells during liver regeneration 19 20 .

Elevated sE-Cad was observed in the serum or plasma of patients with gastric carcinoma 21 , bladder cancer 22 , non-small cell lung cancer 23 , melanoma 24 , late-stage colorectal carcinoma 5 , and hepatocellular carcinoma 25 . However, higher levels of that cadherin have also been found in gastroesophageal reflux disease 26 , multiorgan dysfunction 27 , endometriosis 28 , familial adenomatous polyposis 25 , and acute pancreatitis 29 . Higher amounts of the serum sN-CAD have been described in a group of cancerous patients suffering from prostate carcinoma, breast cancer, ovarian cancer, and gastrointestinal carcinoma, and have been mentioned as being present in diabetes and liver cirrhosis (data not shown) as well 3 . The present study exhibited a higher plasma concentration of sE-CAD in the liver cancer group than the healthy group. This is consistent with the results reported by Sayoma et al. 25 .

Moreover, the level of the marker was observed to be lower in the echinococcosis group than the healthy control group. This suggests that sE-cadherin would be a valuable marker of HCC not only because of its association with early recurrence and extrahepatic metastasis 25 , but also owing to its ability to distinguish between liver cancer and echinococcosis. In the present study, the plasma sN-CAD concentration in liver cancer was also observed to be lower than that in the healthy group. These results are difficult to explain and require further analysis. Moreover, they seem to be inconsistent with the results reported by Derycke et al. 3 . However, there is no information about the presence of liver carcinoma in the cancerous group examined by them.

The lower levels of the plasmas sN-CAD and sE-CAD in echinococossis patients than in healthy subjects could be explained by the ability of Echinococcus granulosus to evade certain defence mechanisms by such means as modulating the host's immune system and resisting the host's proteolytic enzymes by dealing efficiently with, e.g. MMP-9 19 30 . Discriminant analysis revealed that the association of two or more markers significantly increased their efficiency. These results seem to encourage other scientists to combine two or more markers, which are not effective enough when used separately.

Echinococcosis affects the concentration of soluble sE-CAD fragments and Gal-3 in plasma. sE-CAD can be considered as a marker for differentiating between liver cancer and echinoccocossis, a parasitic liver disease similar in symptoms. Further study is required to confirm these preliminary results.

The authors declare that they have no competing interests.

All authors participated in the design of the study. MPP applied for and obtained the approval from an ethics committee. MPP and PZ participated in collecting clinical data, performed the clinical diagnosis and samples collecting. JG carried out the ELISA determination, the statistical analysis and drafted the manuscript. MPP, PW, PZ and JP performed reviewing and editing of the manuscript. JP and PW participated in coordination of the experiment. All authors read and approved the final version of manuscript.