Ricerc@Sapienza

Tissue interstitial fluid (TIF), as the liquid microenvironment of cancer cells, reflects the molecular imprint of proteins that are related to cancer and represents a reliable link among tumor markers expression and body fluids circulation. Since tumors have a high degree of immunogenicity, many tumor markers released in the TIF, once drained into local lymph nodes, may act as tumor-associated antigens (TAAs) and activate B-cells which in turn generate tumor antigen-specific antibodies. The generation of these antibodies leads to a very effective and specific biological amplification of a tumor marker. Therefore, their serological identification could be an effective strategy for the early diagnosis of a cancer.
Late clinical presentation and limited treatment options make the early diagnosis of intrahepatic cholangiocarcinoma (iCCA) by noninvasive methods a current clinical challenge. Here, as preliminary results, we unveil a peculiar proteome profile of TIF isolated in iCCA patients. This analysis represents a valuable molecular platform in the characterization of both immune and non-immune iCCA-associated proteins. Therefore, driven by our preliminary results, we designed the present proposal in search of effective circulating biomarkers and potential therapeutic targets. Particularly, we firstly aim to quantify circulating tumor markers from the proteins found to be aberrantly expressed in the iCCA TIF. Then, by immunoproteomic approach, we aim to identify TAAs in the TIF. Finally, identified iCCA-specific antigens will be tested for their capability to isolate and quantify specific antibodies in serum. The ultimate scope of this project will be the development of a specific and sensitive biomarkers panel by combining tumor markers and tumor-specific antibodies.