98 - Freie Mitteilung
17. Mai 2019, 14:15 - 15:45, Kursaal Arena, 5. OG
Multimarker analysis of 23 biomarkers involved in tumor progression in colorectal cancer
A. Polutak1, A. Cwikla1, S. Däster2, S. Soysal1, N. Tosti1, G. C. Spagnoli1, G. Iezzi1, 3, S. Piscuoglio1, S. Eppenberger-Castori1, L. Terracciano1, M. von Flüe1, R. A. Droeser1, Presenter: A. Cwikla1 (1Basel, 2Sydney/AUS, 3Lugano)
Colorectal cancer (CRC) is the third most common cancer in the world and one of the major cause of cancer related death. There is still an ongoing debate about the adjuvant treatment in stage II cancer. Based on several biomarker studies an immunoscore that apparently outperforms the TNM classification was developed and validated. In our previous research, we could demonstrate the prognostic role of different immune biomarkers in CRC. The aim of the present study was to design a multi-marker Cox regression model, which would help in generating a scoring system supporting personalized clinical decisions.
We analyzed the protein expression levels of 23 selected biomarkers in a TMA representative for 1414 CRC patients. A Spearman’s correlation matrix was built to analyse the interactions between the immunomarkers and the clinico-pathological characteristics. Several hazard Cox regression models were applied to investigate the prognostic impact of the identified clusters.
Based on a modest to strong spearman’s correlation (r>0.35) we could identify the following clusters of biomarkers: MPO, CD15, IL-17 (A); CD68, CD16, CD66b (B); Granzyme, CD8, TIA-1 (C); CD3, CD57, MUM1 (D); TIL, IL-22/TIL, CXCR4 (E). With respect to survival, the Cox regression analyses in our cohort display CD8 still as major independent prognostic factor on top of the clinic-pathological features with (HR 0.70; 95% CI 0.56-0.88; p=0.002). Of interest however are the results obtained using model C. In this model TIA-1 expression showed an independent value, higher levels being also associated with good prognosis (HR 0.65; 95% CI 0.49-0.88; p=0.004 ) letting hypothesize that the presence of TIA-1 highly expressing cells might eliminate cytotoxic lymphocytes.
In our multimarker analyses, high expression of TIA-1 and of CD8 were found to be the most strongly associated immunomarkers with good prognosis independently from the clinicopathological feature of the CRC patients. We plan to validate our findings by the analysis of TCGA data.