Innovative use of genes as biomarkers for intrahepatic cholangiocarcinoma (iCCA) could determine response to chemotherapy, according to an article recently published in Stem Cell Research & Therapy.

“We discovered that 4-key-genes are associated with self-renewal ability of [iCCA] and their overexpression could enhance chemoresistance of cholangiocarcinoma cells,” the authors wrote.

This experimental research found that a total of 4 genes associated with stemness, including COX8A, MRPL11, MRPS34, and SDHAF2, could be potential predictors of prognosis for patients with iCCA, as described by Huang and colleagues.

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Multiple confirmatory functional tests such as real-time quantitative reverse transcription, western blot, metabolomic analysis, flow cytometric analysis, immunohistochemistry, cell counting kit-8 assay, and sphere formation assay further determined these genes exhibit upregulation in patients with iCCA since they seem to play a key role on the self-renewal property of this tumor.

Moreover, the study found that stemness is deeply related to methionine adenosyltransferase 2A and methionine metabolism in general.

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The authors also noticed that individuals who undergo a diet with a limited intake of methionine might further benefit from adjuvant transarterial chemoembolization (TACE). This result yields valuable insight into this neoplastic disease and its response to chemotherapy, which could dictate novel guidelines and targets for this therapeutic scheme.

To achieve these results, the researchers crafted a nomogram for patients with iCCA receiving TACE based on multivariate analysis and estimated the results of the methionine consumption regulation using clinical data, later confirmed by in vivo experiments on mice. Notably, patients with nomogram scores of 135 or above showcased the highest response to the dietary change, especially when overexpression of the 4-key-genes was present.

In the presence of disease with great mortality, and limited treatment options, such as iCCA, these results are of special interest. Although surgical resection of this tumor remains the preferred approach, previous literature reports suggest that adjuvant chemotherapy may be beneficial. Regardless, a reliable method to measure the improvement of the surgical outcomes when performing TACE is not yet clear.

“Their recent study further indicated that this [iCCA] nomogram can also be utilized to select candidates who might be suitable for adjuvant TACE,” the authors concluded.


Huang L, Xu D, Qian Y, et al. A gene signature is critical for intrahepatic cholangiocarcinoma stem cell self-renewal and chemotherapeutic response. Stem Cell Res Ther. Published online July 15, 2022. doi:10.1186/s13287-022-02988-9