The usage of bioinformatics applications to explain microenvironmental and genetic changes driving progression of colon cancer from stage II to stages III and IV

• Thesis title in Czech: ?
• Thesis title in English: The usage of bioinformatics applications to explain microenvironmental and genetic changes driving progression of colon cancer from stage II to stages III and IV
• Academic year of topic announcement: 2025/2026
• Thesis type: dissertation
• Thesis language: angličtina
• Department: Biomedical Center (14-560)
• Supervisor: Mgr. Filip Ambrożkiewicz, Ph.D.
• Advisors: Andriy Trailin, M.D., DSc.

Guidelines

The Prof. Kari Hemminkiʼs research team is recruiting applicants for PhD position under fully funded scholarship by Charles University.
Research topic summary:
More than half of new colon cancer (CC) patients present at diagnosis with metastases in local lymph nodes (LNs) (stage III) and distant metastases (stage IV). Survival in CC is successively worse in stages III and IV compared with nonmetastatic stage II. Treatment of stage II CC consists of surgical resection and then adjuvant chemotherapy is used in patients with a high-risk of recurrence. Existing histopathological criteria for high-risk stage II patients are not conclusive. Moreover, in the past two decades evidence has been provided that the main parameters associated with dissemination to metastasis may be immune and not tumor-related. Increasing evidence suggests the importance of tumor immune microenvironment, which is presented with scattered immune cells and tertiary lymphoid structures inside and around the tumor. Underlying mechanisms for the development of distant metastases with and without the involvement of RLNs require further investigation. However, the prognostic significance of tumor immune microenvironment in CC is still inconclusive. Vascular system is a major active player in the metastatic process, although, the relative importance of blood and lymphatic angiogenesis in different regions of primary tumor and regional LNs in CC needs refinement.
It is assumed that cancer cells originate as a result of the accumulation of genetic and epigenetic changes, which can activate oncogenes and/or inactivate tumor suppressor genes. LN and distant metastases of CC showed discordant mutational status an overall increase in clonality compared with the primary tumor in many patients. Tumor mutation burden in LNs and distant metastases compared to primary CC is not known.
Our hypothesis posits that comparison of histopathological characteristics, immune microenvironment and angiogenesis in primary colon cancer and draining LNs along with mutational analysis between patients with stages II-III-IV CC will reveal mechanisms of metastasis. Such integrative approach may help to delineate contribution of tumor and immune cells parameters in the metastasis, discover biomarkers for the risk of locoregional and systemic relapse in stage II CC and improve risk stratification of CC leading to precise indication of adjuvant therapy.

Preliminary scope of work in English

Candidates are welcome if they have the background and interest in Histology, Microscopy, Immunology, Molecular genetics, Bioinformatics and Statistics.
Required communication skills include the ability to organize and present information effectively, as well as proficiency in written and spoken English.
Applications are open until the 30th April 2025 and the start of the study is 1st October 2025.
Please send your updated CV, cover letter, and contact information for two referees to:
Andriy Trailin, MD, DSc, Laboratory of translational cancer genomics, School of Medicine and Biomedical Center, Charles University, Pilsen, Czech Republic, [e-mail]
Filip Ambrozkiewicz, PhD, Laboratory of translational cancer genomics, School of Medicine and Biomedical Center, Charles University, Pilsen, Czech Republic, [e-mail]