Impact of Spatially Heterogeneous Trop-2 Expression on Prognosis in Oral Squamous Cell Carcinoma

Abstract

Oral cancer often presents with aggressive behavior and a high risk of recurrence and metastasis. For oral squamous cell carcinoma (OSCC), which is the most frequent histological subtype, therapy strategies include surgery, radiation therapy, chemotherapy, immune checkpoint inhibitors, and EGFR inhibitors. Recently, a Trop-2 antibody-drug conjugate (ADC) has been approved in the United States of America for the treatment of advanced triple-negative breast cancer. However, this ADC has also been tested in other solid tumors including head & neck squamous cell carcinoma. The prognostic impact of Trop-2 has already been reported for several cancers. We studied the prognostic influence of Trop-2 protein expression on OSCC patients’ survival. The cohort comprised n = 229 OSCC patients with available archived tumor tissue and corresponding non-neoplastic oral mucosa tissue. Using immunohistochemistry, we investigated Trop-2 expression in both the central and peripheral regions of each tumor and in corresponding non-neoplastic oral mucosa. In patients suffering from OSCC with combined high central and low peripheral Trop-2 expression, five-year overall survival (OS) was 41.2%, whereas 55.6% of OSCC patients who presented lower central and/or higher peripheral tumoral Trop-2 expression were alive after five years (p = 0.075). In multivariate Cox regression, the expression pattern of high central tumoral and lower peripheral Trop-2 expression was significantly correlated with impaired OS (HR = 1.802, 95%-CI: 1.134–2.864; p = 0.013) and recurrence-free survival (RFS) (HR = 1.633, 95%-CI: 1.042–2.560; p = 0.033), respectively, when adjusting for co-variables. Hence, Trop-2 may serve as an independent prognostic biomarker in OSCC. In subsequent studies, the pathophysiological meaning of downregulated Trop-2 expression in the OSCC periphery has to be analyzed.

TROP2 is highly expressed in triple-negative breast cancer CTCs and is a potential marker for epithelial mesenchymal CTCs

“…TROP2 may serve as an independent prognostic biomarker in patients with glioblastoma and oral squamous cell carcinoma. 48 , 49 Furthermore, previous studies have shown that the upregulation of TROP2 plays a critical role in human cancer growth and that tumor development is quantitatively driven by TROP2 expression levels. 50 , 51 Moreover, TROP2 high expression is a suitable marker for stratifying patients with a high risk of colorectal cancer.…”

Therapeutic Targeting Tongue Squamous Cell Carcinoma via ICAM1 Antibody-Drug Conjugates in Preclinical Models

“…More importantly, we have validated that ICAM1 antigens overexpressed on the surface of human TSCC cells can facilitate rapid and e cient cellular internalization of its monoclonal antibodies, which is a critical consideration factor for ICAM1-ADC development. Besides ICAM1, other cell membrane proteins such as nectin-4 67 , folate receptor 68, 69 , TROP2 70 , and epidermal growth factor receptor (EGFR) 71,72 have also been reported as promising molecular targets for oral squamous cell carcinoma, all of which have been utilized for clinically-approved ADCs (Enfortumab vedotin, Mirvetuximab Soravtansine, and Sacituzumab govitecan) or ADCs in clinical trials (ABT414) 73 . Thus, we compared the levels of nectin-4, folate receptor and TROP2 overexpression in comparison with ICAM1, and found they are approximately 8.01%-98.2% lower.…”

Serum metabolomics characteristics and fatty-acid-related mechanism of cirrhosis with histological response in chronic hepatitis B

“…Then, the PPARγ antibody (1:300 dilution, ab59256, Abcam) was also processed following the same conditions and steps. The stained slides were scanned and quantified using the HALO Highplex FL (Indica Labs; Albuquerque, NM) analysis module of Halo software ( Erber et al, 2021 ).…”