The expression of the PPFIA4 oncogene is generally higher in samples from patients with cholangiocarcinoma compared to normal patients’ samples, according to a new study published in the journal Frontiers in Oncology. Moreover, the study found that patients with a high PPFIA4 expression had a poor prognosis.

“The present study may provide a valid prognostic model for bile duct cancer to inform better clinical management of patients,” wrote the authors of the article.

The team from China wanted to develop a new prognostic model for cholangiocarcinoma, the prognosis of which is very poor. The 5-year survival rate after diagnosis for all hepatobiliary malignancies is about 10%, and close to 0 for those diagnosed with unresectable tumors. 

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The researchers focused on 6 hypoxia-related genes and calculated the risk score for each of the 36 patients from whom they obtained samples.

Read more about the prognosis of cholangiocarcinoma

They found that the prognosis of patients who had high-risk scores was worse than in patients who had low-risk scores. Multivariate analysis confirmed the risk score as being an independent predictor of prognosis.

“The hypoxia-related prognostic model . . . exhibited excellent performance in predicting overall survival in [cholangiocarcinoma],” the researchers wrote. 

They also reported that the results of protein-protein interaction networks they constructed suggested hypoxia-related genes to be critical in regulating the hypoxic state. 

Moreover, mutations in the isocitrate dehydrogenase (NADP(+)) 1 (IDH1) gene were more common in the high-risk group, they found. 

Finally, the gene set enrichment analysis showed that some metabolic pathways were upregulated while immune response processes were downregulated in the high-risk group. “These factors may be potential reasons for the high-risk group with worse prognosis,” the researchers wrote.

When they analyzed processes related to the different immune regulation in the 2 groups, they found that the expression of immune checkpoint-related genes was different.


Sun Q, Wang H, Xiao B, Xue D, Wang G. Development and validation of a 6-gene hypoxia-related prognostic signature for cholangiocarcinoma. Front Oncol. 2022;18;12:954366. doi:10.3389/fonc.2022.954366