A Study of iNOS and PCNA Expression on the Aggressiveness of Oral Squamous Cell Carcinoma (OSCC)

Abstract

INTRODUCTION/OBJECTIVE: Oral Squamous Cell Carcinoma (OSCC) is one of the world's most aggressive cancers. Large-scale NO generation is facilitated by Inducible Nitric Oxide Synthase (iNOS) in chronic inflammatory diseases, including cancer. The 36-kDa non-histone nuclear peptide, also known as Proliferating Cell Nuclear Antigen (PCNA), is important for DNA replication. In human OSCC, iNOS and PCNA are useful indicators of induction, progression, and cell proliferation that influence the aggressiveness and growth rate of cancer. Thus, this study aimed to compare the expression of PCNA and iNOS in various OSCCs. METHODS: The study design was a retrospective study using 30 tissue blocks from OSCC patients immunohistochemically stained with iNOS and PCNA antibodies and divided into ten well-differentiated, ten moderatelydifferentiated, and ten poorly-differentiated OSCC. PCNA-positive cells and iNOS infiltration intensity were measured. One-way ANOVA with multiple comparisons was done using Tukey's Post Hoc Test to compare the expression of PCNA and iNOS in various OSCCs, and a Chi-square test was performed for score values in various OSCCs. A P-value < 0.05 was considered significant. RESULTS: With varying histopathological grades of OSCC, the infiltration intensity of iNOS increased from weak expression in well-differentiated OSCC (2.3 ± 0.78) to strong expression in poorly-differentiated OSCC (5 ± 1.18). In addition, PCNA-positive cells were observed and showed higher expression, increasing from weak expression in well-differentiated OSCC (466 ± 31.35) to strong expression in poorly-differentiated OSCC (673 ± 76.27). It was revealed that the expression increased as OSCC progressed (P-value < 0.01). DISCUSSION: The identification of reliable biomarkers that can predict tumor behavior, prognosis, and response to therapy is critical for improving patient outcomes. In this context, they are considered key immunohistopathological markers in OSCC. Understanding the role of iNOS and PCNA in OSCC can enhance diagnostic accuracy and offer new avenues for targeted therapies. These markers may serve not only as tools for evaluating tumor proliferation and invasiveness but also as indicators for therapeutic response, particularly in the context of novel anti-cancer therapies aimed at modulating the tumor microenvironment or cell cycle regulation. Furthermore, their utility in identifying high-risk patients with a propensity to metastasize underscores their clinical relevance in stratifying patient care and informing personalized treatment plans. CONCLUSIONS: These results demonstrated that elevated iNOS and PCNA expression may serve as prognostic indicators for OSCC. This will improve clinical decision-making, guiding therapeutic interventions and enhancing patient prognosis in OSCC management.