Proteomic analysis of breast cancer based on immune subtypes

Yeonjin Jeon; GunHee Lee; Hwangkyo Jeong; Gyungyub Gong; JiSun Kim; Kyunggon Kim; Jae Ho Jeong; Hee Jin Lee

doi:10.1186/s12014-024-09463-y

Proteomic analysis of breast cancer based on immune subtypes

Clin Proteomics. 2024 Feb 29;21(1):17. doi: 10.1186/s12014-024-09463-y.

Authors

Yeonjin Jeon^#¹, GunHee Lee^#¹, Hwangkyo Jeong², Gyungyub Gong¹, JiSun Kim³, Kyunggon Kim⁴, Jae Ho Jeong⁵, Hee Jin Lee^{6

7

8}

Affiliations

¹ Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
² Prometabio Research Institute, Prometabio co., ltd, Hanam-Si, Gyeonggi-Do, Republic of Korea.
³ Division of Breast Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁴ Department of Digital Medicine, University of Ulsan College of Medicine, Seoul, Korea.
⁵ Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. jaeho.jeong@amc.seoul.kr.
⁶ Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. backlila@gmail.com.
⁷ Biomedical Sciences, Asan Medical Institute of Convergence Science and Technology (AMIST), Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. backlila@gmail.com.
⁸ NeogenTC Corp, Seoul, Korea. backlila@gmail.com.

^# Contributed equally.

Abstract

Background: Immunotherapy is applied to breast cancer to resolve the limitations of survival gain in existing treatment modalities. With immunotherapy, a tumor can be classified into immune-inflamed, excluded and desert based on the distribution of immune cells. We assessed the clinicopathological features, each subtype's prognostic value and differentially expressed proteins between immune subtypes.

Methods: Immune subtyping and proteomic analysis were performed on 56 breast cancer cases with neoadjuvant chemotherapy. The immune subtyping was based on the level of tumor-infiltrating lymphocytes (TILs) and Klintrup criteria. If the level of TILs was ≥ 10%, it was classified as immune-inflamed type without consideration of the Klintrup criteria. In cases of 1-9% TIL, Klintrup criteria 1-3 were classified as the immune-excluded subtype and Klintrup criteria not available (NA) was classified as NA. Cases of 1% TILs and Klintrup 0 were classified as the immune-desert subtype. Mass spectrometry was used to identify differentially expressed proteins in formalin-fixed paraffin-embedded biopsy tissues.

Results: Of the 56 cases, 31 (55%) were immune-inflamed, 21 (38%) were immune-excluded, 2 (4%) were immune-desert and 2 (4%) were NA. Welch's t-test revealed two differentially expressed proteins between immune-inflamed and immune-excluded/desert subtypes. Coronin-1A was upregulated in immune-inflamed tumors (adjusted p = 0.008) and α-1-antitrypsin was upregulated in immune-excluded/desert tumors (adjusted p = 0.008). Titin was upregulated in pathologic complete response (pCR) than non-pCR among immune-inflamed tumors (adjusted p = 0.036).

Conclusions: Coronin-1A and α-1-antitrypsin were upregulated in immune-inflamed and immune-excluded/desert subtypes, respectively. Titin's elevated expression in pCR within the immune-inflamed subtype may indicate a favorable prognosis. Further studies involving large representative cohorts are necessary to validate these findings.

Keywords: Breast cancer; Immune subtype; Proteomic analysis.

Abstract

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