Serum thrombospondin-1 serves as a novel biomarker and agonist of gemcitabine-based chemotherapy in intrahepatic cholangiocarcinoma.

Abstract

BACKGROUND:

At present, the first-line treatment for advanced intrahepatic cholangiocarcinoma (ICC) is gemcitabine combined with cisplatin, but a considerable portion of ICC patients exhibit resistance to gemcitabine. Therefore, finding sensitisers for gemcitabine chemotherapy in ICC patients and predicting molecular markers for chemotherapy efficacy have become urgent needs.

METHODS:

In this study, PDX models were established to conduct gemcitabine susceptibility tests. The selected PDX tissues of the chemotherapy-sensitive group and drug-resistant group were subjected to transcriptome sequencing and protein chip technology to identify the key genes. Sixty-one ICC patients treated with gemcitabine chemotherapy were recruited for clinical follow-up validation.

RESULTS:

We found that thrombospondin-1 (TSP1) can predict gemcitabine chemosensitivity in ICC patients. The expression level of TSP1 could reflect the sensitivity of ICC patients to gemcitabine chemotherapy. Functional experiments further confirmed that TSP1 can increase the efficacy of gemcitabine chemotherapy for ICC. A mechanism study showed that TSP1 may affect the intake of oleic acid by binding to the CD36 receptor.

CONCLUSIONS:

In summary, we found a key molecule-TSP1-that can predict and improve the sensitivity of ICC patients to gemcitabine chemotherapy, which is of great significance for the treatment of advanced cholangiocarcinoma.

• Authors: Dong-Yang Ding, Xiao-Jie Gan, Jia-Ning Zhang, Guo-Jun Hou, Qi-Fei Tao, Da-Peng Sun, Wen Li, Yuan Yang, Wen-Bin Ding, Jian Yu, Lei Liu, Fu Yang, Wei-Ping Zhou, Sheng-Xian Yuan
• Journal: British journal of cancer (Br J Cancer) Vol. 128 Issue 5 Pg. 907-917 (03 2023) ISSN: 1532-1827 [Electronic] England
• PMID: 36526676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Gemcitabine
• Deoxycytidine
• Cisplatin
• Biomarkers
• Thrombospondins

Topics

• Humans
• Gemcitabine
• Deoxycytidine
• Cholangiocarcinoma (pathology)
• Cisplatin
• Biomarkers
• Bile Ducts, Intrahepatic (pathology)
• Bile Duct Neoplasms (pathology)
• Thrombospondins (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)