The high expression of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), a known cancer stem cell marker, is possibly a good prognostic indicator in intrahepatic cholangiocarcinoma, according to a new study published in Pathology Research and Practice.

After hepatocellular carcinoma, intrahepatic cholangiocarcinoma represents the second most commonly diagnosed primary liver cancer. However, studies show that intrahepatic cholangiocarcinoma does not carry a good prognosis: the risk of recurrence is high and the 5-year overall survival rate, even with curative resection and adjuvant therapy, is merely 20% to 40%.

LGR5 has been known to be a cancer stem cell marker in the esophagus, stomach, colon, and breast. Previous studies demonstrated that high LGR5 expression was associated with higher differentiation and a better prognosis in pancreatic ductal adenocarcinoma and colorectal carcinoma. In this study, the research team set out to analyze the presence or absence of LGR5 expression in intrahepatocellular carcinoma.

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The research team identified 32 patients who underwent surgical resection for intrahepatic cholangiocarcinoma between January 2014 and December 2020. Seven cases were omitted because they had elements of hepatocellular carcinoma or gallbladder carcinoma. Hence, a total of 25 patients took part in the study. The research team studied the 25 samples of intrahepatic cholangiocarcinoma provided and determined the levels of LGR5 expression in them. 

The results demonstrated higher LGR5 expression among well-differentiated to moderately-differentiated adenocarcinoma compared to poorly-differentiated adenocarcinoma. In addition, the small duct type demonstrated lower LGR5 expression compared to the large duct type. Statistical studies indicated that patients with high expression of LGR5 independently showed better overall survival for intrahepatic cholangiocarcinoma.

“Our results suggest that high LGR5 expression is an independent prognosis factor in [intrahepatic cholangiocarcinoma]. However, the detailed molecular mechanism of LGR5 in this disease remains unclear, and further analysis is warranted,” the authors concluded.


Yoshizawa T, Uehara T, Iwaya M, et al. Correlation of LGR5 expression and clinicopathological features in intrahepatic cholangiocarcinomaPathol Res Pract. Published online March 3, 2022. doi:10.1016/j.prp.2022.153832