In this study, the gene expressions of Cat-B and Cav-1 were significantly higher in the OLP and OSCC samples compared to the controls. They were also higher for OSCC than for OLP, along with an increase in the stage and grade of the lesions. Unlike Cat-B, such an increase was gradual for Cav-1. The gene expressions of Cat-B and Cav-1 in OLP were not associated with clinical indices of the lesion, including its severity as per Thangprasom scores and duration, as well as smoking and the presence of cutaneous lichen planus. In addition, the expressions were independent of age and gender. There was a correlation between the gene expressions of Cat-B and Cav-1 in OSCC and OLP, and the correlation was more significant in OSCC.
Given that OLP is inherently recognized as an oral malignancy and OSCC treatment varies based on clinical stage, pathology, and metastasis, determining the behavioral evolution of these lesions is fundamental in choosing the best treatment. Numerous studies have been carried out on various markers for their possible role as predictors of malignant OLP changes as well as on the OSCC prognosis in order to predict their behavior.
In a 2010 study, Yang et al. examined the expression of Cat-B in tissue samples from 30 OSCC patients using three methods, namely immunohistochemistry (IHC), RT-PCR and the Western blot analysis. According to their study, the gene expression of Cat-B was associated with metastasis to regional lymph nodes (5).
Also in 2012, Chen et al. compared changes in the gene expression of Cat-B with the clinicopathological indices of 444 patients with OSCC and found a significant relationship between a single nucleotide pleomorphism (SNP) of Cat-B and an increased risk of OSCC. They also reported a significant relationship between the expression of Cat-B and the grade and stage of lesions in OSCC patients, although this increase was not gradual for the grade (12).
Satelur (2017) examined the expression of Cat-B in 50 OLP patients as a case group along with 10 OSCC patients and 10 healthy individuals as a control group by IHC. The Cat B-associated staining intensity in the stromal region and basal cells of both lesions was similar and confirmed the role of this marker in OSCC carcinogenesis in the epithelial-connective tissue model. On the other hand, the gene expression of Cat-B in connective tissue as a transmitter of degenerating signals to epithelial cells was included in the pathogenesis of OLP and in the possibility of malignancy. However, no study has been conducted on the relationship between the clinical indices of OLP as well as the clinicopathological indices of OSCC and the gene expression of Cat-B (13).
The gene expressoin of Cav-1 in oral tissues has been shown in various studies to affect the development of OSCC from dysplasia, which is consistent with the clinicopathological indices of OSCC. Hung et al. (2003) immunohistochemically examined 96 tissue samples, including normal oral tissue, precancerous lesions, OSCC tissue and its metastatic type. However, they did not confirm the effect of Cav-1 expression in the primary OSCC lesions and their metastatic type. They also reported a significantly lower Cav-1 expression in metastatic types as well as no association of Cat-1 expression with age, gender, smoking, stage and grade of the lesions (8). In the present study, the clinical indices including age, gender, severity and duration of lesions had no effect on gene expression in OSCC. However, gene expression was significantly associated with the stage and grade of the OSCC lesions.
Kato et al. (2020) immunohistochemically examined the gene expression of Cav-1 in tissue samples from 80 OSCC patients and compared it to 15 samples from metastatic lymph nodes and showed that there was a significant association between the expression of Cav-1 in OSCC and metastasis of cell differentiation and lesion invasion. They therefore suggested to use Cav-1 expression for the prognosis of OSCC (14).
There is still some controversy about the relationship between the gene expression of Cav-1 and the stage and grade of lesions in OSCC. According to some studies, as the stage and grade of the lesion increase, so does the expression of Cav-1. Even the expression of this gene has been inversely related to the survival of OSCC patients (7, 15). In the study by Routray et al., however, the increase in Cav-1 expression was linked to an improved prognosis (6).
Ashkavandi reported the gene expression of Cav-1 in the cytoplasm of 81 biopsy samples from various oral lesions including hyperkeratosis, dysplastic epithelium, OSCC and OLP, with the gene expression of Cav-1 only being significant in OSCC (92%), while being 4% in OLP and increased proportionally with hyperkeratosis to dysplastic epithelium and OSCC (7). In addition, both gene expressions were high in OSCC and OLP and low in controls, which is consistent with the results of our study in which the gene expression of Cav-1 gradually increased in OSCC.
Among the studies reviewed in the present work, only Chen and Yang performed genetic testing on the samples. Given that the study of gene expression using the qRT-PCR method is more accurate than directly measuring the amount of marker in the tissue or observing its staining pattern and that it depends less on the competency of the examiner, we expect the results of the present work to be more reliable. In contrast to IHC, however, this method cannot detect the position of the gene and the expression of markers in the cell due to the loss of cell structure in the laboratory. Therefore, the best and most accurate method is to use PCR and IHC. A gradual increase in gene expression with increasing stage and degree of OSCC pathology was only observed in Cav-1, while the Cat-B expression decreased in grade 1 compared to grade 2, which could not be justified.
Overall, although in our study the gene expressions of Cat-B and Cav-1 increased in OLP and OSCC, we observed a different and contradicting result for Cav-1. This can be explained by noting that in some genes like Cav-1, the multiple function is related to different parts of the structure of this marker that can result in either susceptibility or resistance to cancer (7). The Tye-13 domain of Cav-1 causes cells to grow, while its scaffolding domain suppresses the tumor (9).