The evolving treatment and biomarkers of hepatocellular carcinoma

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Oulu University Hospital, lecture hall 1 and 2. Remote access:

Topic of the dissertation

The evolving treatment and biomarkers of hepatocellular carcinoma

Doctoral candidate

Licentiate of Medicine Valtteri Kairaluoma

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, Medical Research Center Oulu

Subject of study



Professor Caj Haglund, University of Helsinki


Professor Juha Saarnio, University of Oulu

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The evolving treatment and biomarkers of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most lethal cancer worldwide. Risk factors for HCC include hepatitis viruses, especially in Eastern countries. In Western countries, heavy alcohol consumption and metabolic liver disease are major causes of liver cirrhosis and cancer. The detection of HCC is challenging because the symptoms often appear at later stages of the cancer.

The tumoral microenvironment plays an important role in tumor progression, growth and metastasis. Tumor budding, defined as a single tumor cell or a cell cluster of up to four tumor cells, is associated with poor prognosis in several cancer types. Tumor-Stroma Ratio (TSR) is defined as the percentage of tumor cell component relative to the surrounding stroma. Low TSR in tumor tissue has been recognized as an important factor for tumor prognosis in various cancer types.

Toll-like receptors (TLRs) are innate immunity receptors that are involved in bacterial and viral recognition but also have a role in diverse vital functions, adaptive immunity, and carcinogenesis.

This thesis examined the treatment trends and results of HCC patients treated in Oulu University hospital in 1983–2018. Tumor-Stroma ratio and tumor budding were examined from Hematoxylin and Eosin-stained (HE) histological samples that were originally used for diagnostic purposes. The prognostic value of tumor budding, TSR, TLR2, TLR4, TLR5 and TLR8 staining in HCC was evaluated.

Based on our study on the Northern Finland population, the rate of surgical treatment has decreased significantly since the introduction of local treatments and TACE. Compared to other treatments, the surgical resection of HCC has an acceptable complication rate and best long-term survival. We observed that tumor budding, TLR4 and TLR5 are independent factors of poor prognosis in HCC. According to our study, tumor budding is a prognostic factor that can be reliably replicated and routinely analyzed from HE-stained slides. TLR4 and TLR5 are possible therapeutic targets in the future.
Last updated: 1.3.2023