Application of the Interaction between Tissue Immunohistochemistry Staining and Clinicopathological Factors for Evaluating the Risk of Oral Cancer Progression by Hierarchical Clustering Analysis: A Case-Control Study in a Taiwanese Population

Hui-Ching Wang; Meng-Chun Chou; Chun-Chieh Wu; Leong-Perng Chan; Sin-Hua Moi; Mei-Ren Pan; Ta-Chih Liu; Cheng-Hong Yang

doi:10.3390/diagnostics11060925

Application of the Interaction between Tissue Immunohistochemistry Staining and Clinicopathological Factors for Evaluating the Risk of Oral Cancer Progression by Hierarchical Clustering Analysis: A Case-Control Study in a Taiwanese Population

Diagnostics (Basel). 2021 May 21;11(6):925. doi: 10.3390/diagnostics11060925.

Authors

Hui-Ching Wang^{1

2

3

4}, Meng-Chun Chou⁵, Chun-Chieh Wu^{4

6}, Leong-Perng Chan^{3

7

8}, Sin-Hua Moi⁹, Mei-Ren Pan^{1

4}, Ta-Chih Liu¹⁰, Cheng-Hong Yang^{11

12}

Affiliations

¹ Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
² Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
³ Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁴ Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁵ Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁶ Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁷ Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
⁸ Department of Otorhinolaryngology-Head and Neck Surgery, Kaohsiung Municipal Ta-Tung Hospital and Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
⁹ Center of Cancer Program Development, E-Da Cancer Hospital, I-Shou University, Kaohsiung 824, Taiwan.
¹⁰ Department of Hematology-Oncology, Chang Bing Show Chwan Memorial Hospital, Changhua 505, Taiwan.
¹¹ Department of Electronic Engineering, National Kaohsiung University of Science and Technology, Kaohsiung 807, Taiwan.
¹² Ph. D. Program in Biomedical Engineering, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

Abstract

The aim of this single-center case-control study is to investigate the feasibility and accuracy of oral cancer protein risk stratification (OCPRS) to analyze the risk of cancer progression. All patients diagnosed with oral cancer in Taiwan, between 2012 and 2014, and who underwent surgical intervention were selected for the study. The tissue was further processed for immunohistochemistry (IHC) for 21 target proteins. Analyses were performed using the results of IHC staining, clinicopathological characteristics, and survival outcomes. Novel stratifications with a hierarchical clustering approach and combinations were applied using the Cox proportional hazard regression model. Of the 163 participants recruited, 102 patients were analyzed, and OCPRS successfully identified patients with different progression-free survival (PFS) profiles in high-risk (53 subjects) versus low-risk (49 subjects) groups (p = 0.012). OCPRS was composed of cytoplasmic PLK1, phosphoMet, and SGK2 IHC staining. After controlling for the influence of clinicopathological features, high-risk patients were 2.33 times more likely to experience cancer progression than low-risk patients (p = 0.020). In the multivariate model, patients with extranodal extension (HR = 2.66, p = 0.045) demonstrated a significantly increased risk for disease progression. Risk stratification with OCPRS provided distinct PFS groups for patients with oral cancer after surgical intervention. OCPRS appears suitable for routine clinical use for progression and prognosis estimation.

Keywords: oral cancer; progression-free survival; risk stratification.