Prof. Renata Dobrila-Dintinjana is a physician, specialist in internal medicine, subspecialist in medical oncology, Professor at Faculty of Medicine University Rijeka. Her research focused on field of gastrointestinal tumours and supportive cancer care, specially in the field of cachexia-anorexia syndrome and nutrition. She is author of over 100 publications , 2 books, 20 chapters in the book and over 300 abstracts. Member of ASCO, ESMO, AACR, MASCC, IASGO, member and head of some Executive Boards in Croatia and reviewer for journals and projects in the field of Supportive Cancer Care, Palliative Care, Gastrointestinal Cancers and Molecular Oncology.
Osteopontin (OPN) transformation-related protein phosphatase, is expressed by various tumors (breast, lung, gastric, hepatic, colon and prostate) mostly positive correlating with poor disease outcome. The presence of OPN in the tumor milieu is leading to enhanced tumor growth and metastasis with facilitating the adhesion, migration, survival and proliferation of the cancer cells. OPN play significant role in various signaling pathways (Akt, Raf/MEK/ERK , ILK/PI3K/GSK-3β and RAN GTPase/c-Met/PI3 kinase) which all are involved in metastatic potential of various cancers. OPN is also participating in regulation of hypoxia-inducible factor-1α-dependent VEGF expression what is leading to tumor angiogenesis and growth as response to hypoxia . Cancer stem cells (CSCs) are regulating the expression levels of OPN in tumor microenvironment and vice versa OPN is binding receptors expressed on the surface of cancer cells thus affecting the activity of CSCs. CSCs and OPN trough their interaction are participating in remodeling the tumor microenvironment. The genes for OPN are routinely overexpressed in pancreatic ductal adenocarcinoma (PDA) and OPN is significantly elevated in PDA tissue. Elevated serum OPN level may be used as a promising diagnostic tool for early identification of PC with about 77% of accuracy as the predictive marker and in 89% accuracy in distinguishing between tumor and benign tissue. OPN-C mRNA is overexpressed in gastric cancer, and high levels of OPN are connected with increased proliferation, metastasis, and bad prognosis. OPN has much more higher level in plasma of patients with metastatic disease than in patients without metastases. Also, OPN overexpression in gastric cancer is significantly associated with low apoptotic index, high proliferative index, low grade differentiation of tumor. OPN overexpression is independent predictor of tumor recurrence in patients with resected gastric cancer. In HCC, there is elevated expression of serum OPN compared to patients with normal liver function or with liver cirrhosis and chronic hepatitis. Plasma OPN level is one of the leading independent prognostic factors, as in the early stage of HCC, as for predicting tumor recurrence after HCC resection. As in other gastrointestinal cancers, OPN is highly expressed in patients with metastatic hepatic lesions from colorectal cancer (CRC) and its level is significantly associated with poor survival rates. OPN is connected with estrogen related receptor alfa (ERRα) suggesting a role of ERRα in the development and progression of CRC. Multivariate analysis of study data promote OPN expression as an independent prognostic indicator of poor overall survival in patients with gastrointestinal cancers. OPN as a secreted plasma protein or in tumor samples seems to have a greater potential to become diagnostic or/and prognostic marker for prognosis in some cancers, alone or/and in combination with other biomarkers .
FOR AUDIENCE: besides established tumors markers for gastrointestinal cancers, there is huge need for detection of new biomarkers as diagnostic/prognostic tools. The development of each new marker, and its use in clinics is contribute for elucidating the process of carcinogenesis and thus finding the appropriate treatment for each patient.