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

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.

Clinical significance of L1CAM expression and its biological role in the progression of oral squamous cell carcinoma

“…In the present study, however, a significant correlation between L1CAM expression and high histologic grade, greater DOI, cervical LN metastasis, presence of PNI and advanced TNM stage was observed in OTSCC. These results were inconsistent with those of Adnan et al (27). This may be due to difference in the scoring method of immunohistochemical staining.…”

“…In a previous study on OSCC by Hung et al (19), L1CAM overexpression was closely associated with high histological grade of the tumor; however, the association of L1CAM overexpression with other clinicopathological parameters was not assessed. In addition, a recent study by Adnan et al (27) demonstrated that L1CAM expression was not correlated with any clinicopathological parameters and survival of patients in OSCC. In the present study, however, a significant correlation between L1CAM expression and high histologic grade, greater DOI, cervical LN metastasis, presence of PNI and advanced TNM stage was observed in OTSCC.…”

The Harmonious Inhibitory Effect of Natural Drug Amygdalin (Vitamin B17) and Chemotherapy(cisplatin) on Oral Squamous Cell Carcinoma Cell Line

“…(29) OSCC, which affects the epithelial layer of the oral cavity, is a common malignant tumor of the head and neck with low survival rates and high risks of recurrence. (30) Clinically, OSCC includes lip cancer, which accounts for the majority of OSCC, and intra-oral cancer, which mainly affects the tongue. (31) In the Middle East, population witnessed a surprisingly accelerated incidence of some cancers, which are often secondary to adverse lifestyle choices and westernization.…”

Developments on the Smart Hydrogel-Based Drug Delivery System for Oral Tumor Therapy

“…HA is the main ligand of the CD44 receptor. Because CD44 is highly expressed in oral cancer cells [ 161 , 162 , 163 ], the addition of HA makes the hydrogel more binding to oral cancer cells and increases the immobility of the hydrogel formed in situ.…”