Tumor stroma Siglec15 expression is a poor prognosis predictor in colon adenocarcinoma

Weixiang Zhan; Fan Bai; Yue Cai; Jianwei Zhang; Ge Qin; Yuqian Xie; Yanhong Deng

doi:10.7150/jca.87618

Tumor stroma Siglec15 expression is a poor prognosis predictor in colon adenocarcinoma

J Cancer. 2023 Sep 18;14(16):2998-3008. doi: 10.7150/jca.87618. eCollection 2023.

Authors

Weixiang Zhan^{1

2

3}, Fan Bai^{1

2

3}, Yue Cai^{1

2

3}, Jianwei Zhang^{1

2

3}, Ge Qin^{1

2

3}, Yuqian Xie^{1

2

3}, Yanhong Deng^{1

2

3}

Affiliations

¹ Department of Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangdong Research Institute of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
³ Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Abstract

Sialic acid binding Ig-like lectin 15 (Siglec15) is considered a novel immune checkpoint and an emerging target for next-generation cancer immunotherapy. However, the significance of Siglec15 and its relationship with programmed death-ligand 1 (PD-L1) in colon adenocarcinoma (COAD) remain unknown. In this study, we analyzed Siglec15 expression within stromal area (SA) and tumor area (TA), and its relationship with tumor-infiltrating lymphocytes (TILs) in COAD and mismatch repair-proficient (MMR-p) COAD. Siglec15 expression was significantly higher in COAD tissues than in normal tissues, and elevated Siglec15(SA) expression, rather than Siglec15(TA) and Siglec15 (whole) expression, was correlated with poor prognosis and inversely correlated with the density of CD8⁺ T cell, both in COAD and MMR-p COAD. Moreover, there were no correlations between Siglec15(SA) and PD-L1(SA), and between Siglec15(TA) and PD-L1(TA), whereas there was positive correlation between Siglec15(whole) and PD-L1(whole). A new immune classification based on the Siglec15(SA)/PD-L1(SA) expression, indicated that patients with Siglec15(SA)^Low/PD-L1(SA)⁺ status had the longest survival times in COAD. Our study highlights that Siglec15(SA) is an independent predictor of poor prognosis and has an immunosuppressive role in COAD and MMR-p COAD tissues. These findings may provide insights into improving responses to immunotherapy-included comprehensive treatments for COAD in the future.

Keywords: PD-L1; Siglec15; colon adenocarcinoma; immune checkpoint; immunotherapy.