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조회746

황희연Heeyoun Hwang

한국기초과학지원연구원

Gastroenterology, 2023 Mar 8;S0016-5085(23)00237-8 | https://doi.org/10.1053/j.gastro.2023.02.045 Refining classification of cholangiocarcinoma subtypes via proteogenomic integration reveals new therapeutic prospects

Soo Young Cho ^1,2,9, Heeyoun Hwang ^3,4,9, Yun-Hee Kim ^1,5,9, Byong Chul Yoo ^1,5, Nayoung Han ⁶, Sun-Young Kong ^1,5,7, Min-Jeong Baek¹, Kyung-Hee Kim ^1,5, Mi Rim Lee ^1,5, Jae Gwang Park ¹, Sung-Sik Han⁸, Woo Jin Lee ^1,8, Charny Park ¹, Jong Bae Park ^1,5, Jin Young Kim ^3,4, Sang-Jae Park^1,8, Sang Myung Woo ^1,5,8

¹Research Institute, National Cancer Center, Goyang, Republic of Korea
²Department of Molecular and Life Science, Hanyang University, Ansan, Republic of Korea
³Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Cheongju, Republic of Korea
⁴Critical Diseases Diagnostics Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea
⁵Department of Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang, Republic of Korea
⁶Department of Pathology, National Cancer Center, Goyang, Republic of Korea
⁷Deparment of Laboratory Medicine, National Cancer Center, Goyang, Republic of Korea
⁸Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, Republic of Korea
⁹These authors contributed equally

Corresponding authors: Jin Young Kim, Sang-Jae Park, Sang Myung Woo

Abstract

Background and aims: Intrahepatic cholangiocarcinomas (iCCs) are characterized by their rarity, difficult diagnosis, and overall poor prognosis. The iCC molecular classification for developing precision medicine strategies was investigated.

Methods: Comprehensive genomic, transcriptomic, proteomic, and phosphoproteomic analyses were performed on treatment-naïve tumor samples from 102 patients with iCC who underwent surgical resection with curative intent. An organoid model was constructed for testing therapeutic potential.

Results: Three clinically supported subtypes (stem-like, poorly immunogenic, and metabolism) were identified. NCT-501 (ALDH1A1 inhibitor) exhibited synergism with nab-paclitaxel in the organoid model for stem-like subtype. The oncometabolite dysregulations were associated with different clinical outcomes in stem-like and metabolism subtypes. Poorly immunogenic subtype harbors the non-T-cell tumor infiltration. Integrated multiomics analysis reproduced not only the three subtypes but also showed heterogeneity in iCC.

Conclusion: This large-scale proteogenomic analysis provides information beyond that obtained with genomic analysis, allowing the functional impact of genomic alterations to be discerned. These findings may assist in the stratification of patients with iCC and in developing rational therapeutic strategies.

논문정보

형식Research article
게재일2023년 03월 (BRIC 등록일 2023-03-28)
연구진국내 연구진
분야 의약학 > 응용의학

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