Skeletal muscle and related protein expression as prognostic factors in thymic squamous cell carcinoma

Abstract

Background: Sarcopenia and its marker, the psoas muscle index (PMI), have attracted attention as prognostic factors for various types of cancers. The fragile X-related 1 (FXR1) gene is highly expressed in myocytes, and FXR1 overexpression is a candidate biomarker for poor survival in several types of cancers. Thymic squamous cell carcinoma (TSQCC) is rare, and no studies assessing its prognostic factors, particularly in terms of skeletal muscle mass and FXR1 expression, are available.

Methods: We retrospectively investigated the prognostic significance of PMI in 34 patients who underwent TSQCC resection, considering the status of FXR1 and tumor programmed death-ligand 1 (PD-L1). PMI was calculated from the bilateral psoas muscle using preoperative computed tomography (CT). Patients were divided into two groups: low PMI (<58.2%, n=17) and normal PMI (≥58.2%, n=17). Immunohistochemical analysis was performed to determine the FXR1 and PD-L1 expression levels.

Results: Low PMI was significantly associated with worse overall survival (OS) (5-year survival rate; 86% vs. 100%; P=0.026) and marginally associated with worse disease-free survival (DFS) (5-year survival rate; 39% vs. 66%; P=0.090) compared with normal PMI. The immunohistochemical analysis revealed that the FXR1 intensity score (0-1+: 6% vs. 0%; 2+-3+: 94% vs. 100%; P=0.31), median FXR1 distribution (95% vs. 90%; P=0.63), and PD-L1 status (high: 47% vs. 59%; P=0.49) were not significantly different between the two groups.

Conclusions: Our findings suggest that PMI might be considered as a potential prognostic factor in TSQCC and that FXR1 is widely expressed regardless of the PMI status. Skeletal muscle mass may play a role in the prognosis of TSQCC.

Keywords: Thymic squamous cell carcinoma (TSQCC); fragile X-related 1 (FXR1) gene; programmed death-ligand 1 (PD-L1); psoas muscle index (PMI); surgery.

Figure 1

Representative hematoxylin and eosin staining of TSQCC according to differentiation and lymphoid infiltration. TSQCC, thymic squamous cell carcinoma.

Figure 2

Representative immunohistochemical staining by FXR1 and PD-L1. (A) According to FXR1 intensity score; (B) PD-L1 intensity score. The primary antibody used for FXR1 was rabbit polyclonal antihuman antibody (clone HPA018246; Sigma-Aldrich, Saint Louis, MO, USA). The staining index of FXR1 was calculated from the intensity score (0, no staining; 1+, weak; 2+, moderate; 3+, strong) and the distribution score (0, no staining; 0.1, 1–9% of cells stained; 0.5, 10–49% of cells stained; and 1 if >50% cells stained). For PD-L1 staining, rabbit immunoglobulin G monoclonal antibody (clone SP142; Spring Bioscience, Pleasanton, CA, USA) was used as a primary antibody. PD-L1 positivity was evaluated based on the intensity and distribution score as with FXR1. FXR1, fragile X-related 1; PD-L1, programmed death-ligand 1.

Figure 3

FXR1 and PD-L1 distribution in the low and normal PMI groups. (A) According to FXR1; (B) PD-L1. FXR1, fragile X-related 1; PD-L1, programmed death-ligand 1; PMI, psoas muscle index.

Figure 4

OS and DFS curves of all cohorts and between two groups according to PMI status. (A) OS curve of all cohorts; (B) DFS curve of all cohorts; (C) OS curves between two groups according to PMI status. (D) DFS curves between two groups according to PMI status. PMI, psoas muscle index; OS, overall survival; DFS, disease-free survival.