High CD44 Immunoexpression Correlates with Poor Overall Survival: Assessing the Role of Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma Patients from the High-Risk Population of Pakistan.

Yumna Adnan,M Sohail Awan,S M Adnan Ali,Hammad A Kayani,Romana Idrees,Hasnain A Farooqui

doi:10.1155/2022/9990489

Abstract

Oral squamous cell carcinoma (OSCC) is a top-ranked cancer in the Pakistani population, and patient survival has remained unchanged at ∼50% for several decades. Recent advances have claimed that a subset of tumour cells, called cancer stem cells (CSCs), are responsible for tumour progression, treatment resistance, and metastasis, which leads to a poor prognosis. This study investigated the impact of CSC markers expression on overall survival (OS) and disease-free survival (DFS) of OSCC patients. Materials and Methods. Immunohistochemistry was used to evaluate CD44, CD133, L1CAM, and SOX2 expression in a well-characterized cohort of 100 Pakistani patients with primary treatment naïve OSCC. The immunoreactivity for each marker was correlated with patient clinicopathologic characteristics, oral cancer risk chewing habits, and survival. The minimum follow-up time for all patients was five years, and survival estimates were calculated using the Kaplan–Meier method and Cox proportional hazards model. Results. In this cohort of 100 patients, there were 57 males and 43 females. The median OS and DFS time durations observed were 64 and 52.5 months, respectively. Positive expression for CD44, CD133, L1CAM, and SOX2 was observed in 33%, 23%, 41%, and 63% of patients. High CD44 expression correlated with decreased OS (P=0.047) but did not influence DFS. However, CD133, L1CAM, and SOX2 had no effect on either OS or DFS. Tonsils, nodal involvement, and AJCC stage were independent predictors of worse OS and DFS both. Conclusion. Of the CSC markers investigated here, only CD44 was a predictor for poor OS. CD44 was also associated with advanced AJCC and T stages. Interestingly, CD133 was significantly lower in patients who habitually consumed oral cancer risk factors.

Highlights

Oral cavity cancer is one of the leading causes of cancerrelated death in South Central Asia, including Pakistan
More than 90% of oral cancers are oral squamous cell carcinomas (OSCC), arising from the squamous epithelia of the oral cavity. e cancer stem cell hypothesis states that cancer stem cells (CSCs) are a subpopulation of multipotent cells at the core of a tumour that is responsible for tumour differentiation, tumour maintenance, and spread to other sites [4]
CSCs are believed to evade or be resistant to conventional treatment and can generate new tumour cells that are genetically identical to the parent tumour. is self-renewal ability of CSCs leads to disease recurrence and treatment failure. e role of CSCs has not been fully elucidated in OSCC [5]

Summary

Introduction

Oral cavity cancer is one of the leading causes of cancerrelated death in South Central Asia, including Pakistan. It is the first and second most common cancer in Pakistani males and females, respectively, and has the second-highest rate of oral cavity cancers worldwide, continuing to be a major public health crisis and a significant hurdle in improving life expectancy [1, 2]. E rationale for the high incidence of oral cavity cancers in Pakistan, and South Asia in general, is the frequent, persistent, and prevalent use of substances classified as oral cancer risk factors. Despite recent advances in imaging technology and treatment modalities, the last few decades have seen limited improvement in the survival rate of oral cancer. CSCs are believed to evade or be resistant to conventional treatment and can generate new tumour cells that are genetically identical to the parent tumour. is self-renewal ability of CSCs leads to disease recurrence and treatment failure. e role of CSCs has not been fully elucidated in OSCC [5]

Methods

Results

Conclusion