Discovery of a Copy-neutral Loss of Heterozygosity Pattern in Perihilar Cholangiocarcinoma With Potential Prognostic Value

Perihilar cholangiocarcinoma (pCCA) is an aggressive bile duct cancer with a poor prognosis (10-40% 5-year survival after resection), that is mostly found in Thailand and has limited prognostic models. Copy neutral loss of heterozygosity (cnLOH) in various cancers affects their progression leading to poorer overall survival. This study aimed to explore cnLOH patterns in individual pCCA patients in order to develop a predictive model for prognostic biomarkers. DNA was extracted from 14 frozen tissues and chromosome microarray (CMA) was performed to analyze cnLOH. Analysis of cnLOH revealed a median of 14 events per sample. The most frequent cnLOH was observed on chromosome 1q, followed by high occurrences on chromosomes 2, 3p, 5q, 6q, 7q, 11q, and 12q. Importantly, we identified several specific cnLOH regions (2p23.2, 2p23.3, and 6p11.1) where alterations were significantly associated with decreased overall survival (p<0.05). These results provide evidence that cnLOH events may contribute to disease progression and influence overall survival in patients with pCCA, indicating a potential role in the underlying molecular mechanisms of this malignancy.