Sangwon Lee, Yeon Ho Choi, Hak Min Kim, Min Ah Hong, Phillip Park, In Hae Kwak, Ye Ji Kang, Kui Son Choi, Hyun-Joo Kong, Hyosung Cha, Hyun-Jin Kim, Kwang Sun Ryu, Young Sang Jeon, Hwanhee Kim, Jip Min Jung, Jeong-Soo Im, Heejung Chae
Received February 27, 2024 Accepted July 9, 2024 Published online July 15, 2024
The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea’s cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.
In Hye Song, Young-Ae Kim, Sun-Hee Heo, Won Seon Bang, Hye Seon Park, Yeon ho Choi, Heejae Lee, Jeong-Han Seo, Youngjin Cho, Sung Wook Jung, Hee Jeong Kim, Sei Hyun Ahn, Hee Jin Lee, Gyungyub Gong
Cancer Res Treat. 2022;54(4):1111-1120. Published online December 21, 2021
Purpose
The expression of major histocompatibility complex class I (MHC I) has previously been reported to be negatively associated with estrogen receptor (ER) expression. Furthermore, MHC I expression, level of tumor-infiltrating lymphocytes (TILs), and expression of interferon (IFN) mediator MxA are positively associated with one another in human breast cancers. This study aimed to investigate the mechanisms of association of MHC I with ER and IFN signaling.
Materials and Methods
The human leukocyte antigen (HLA)-ABC protein expression was analyzed in breast cancer cell lines. The expressions of HLA-A and MxA mRNAs were analyzed in MCF-7 cells in Gene Expression Omnibus (GEO) data. ER and HLA-ABC expressions, Ki-67 labeling index and TIL levels in tumor tissue were also analyzed in ER+/ human epidermal growth factor receptor 2 (HER2)- breast cancer patients who randomly received either neoadjuvant chemotherapy or estrogen modulator treatment followed by resection.
Results
HLA-ABC protein expression was decreased after β-estradiol treatment or hESR-GFP transfection and increased after fulvestrant or IFN-γ treatment in cell lines. In GEO data, HLA-A and MxA expression was increased after ESR1 shRNA transfection. In patients, ER Allred score was significantly lower and the HLA-ABC expression, TIL levels, and Ki-67 were significantly higher in the estrogen modulator treated group than the chemotherapy treated group.
Conclusion
MHC I expression and TIL levels might be affected by ER pathway modulation and IFN treatment. Further studies elucidating the mechanism of MHC I regulation could suggest a way to boost TIL influx in cancer in a clinical setting.
Citations
Citations to this article as recorded by
Estrogen receptor regulation of the immune microenvironment in breast cancer Conor McGuinness, Kara L. Britt The Journal of Steroid Biochemistry and Molecular Biology.2024; 240: 106517. CrossRef
Bioinformatic-Experimental Screening Uncovers Multiple Targets for Increase of MHC-I Expression through Activating the Interferon Response in Breast Cancer Xin Li, Zilun Ruan, Shuzhen Yang, Qing Yang, Jinpeng Li, Mingming Hu International Journal of Molecular Sciences.2024; 25(19): 10546. CrossRef
Hormone Receptor Signaling and Breast Cancer Resistance to Anti-Tumor Immunity Alexandra Moisand, Mathilde Madéry, Thomas Boyer, Charlotte Domblides, Céline Blaye, Nicolas Larmonier International Journal of Molecular Sciences.2023; 24(20): 15048. CrossRef