Abstract
Cutaneous squamous cell carcinoma (cSCC), a malignant proliferation of the cutaneous epithelium, is the second most common skin cancer after basal cell carcinoma (BCC). Unlike BCC, cSCC exhibits a greater aggressiveness and the ability to metastasize to any organ in the body. Chronic inflammation and immunosuppression are important processes linked to the development of cSCC. The tumor can occur de novo or from the histological transformation of preexisting actinic keratoses (AK). Malignant cells exhibit a higher amount of sialic acid in their membranes than normal cells, and changes in the amount, type, or linkage of sialic acid in malignant cell glycoconjugates are related to tumor progression and metastasis. The aim of our study was to investigate the sialyation in patients with cSCC and patients with AK. We have determined the serum levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), beta-galactoside 2,6-sialyltransferase I (ST6GalI), and neuraminidase 3 (NEU3) in 40 patients with cSCC, 28 patients with AK, and 40 healthy subjects. Data analysis indicated a significant increase in serum levels of TSA (p < 0.001), LSA (p < 0.001), ST6GalI (p < 0.001), and NEU3 (p < 0.001) in the cSCC group compared to the control group, whereas in patients with AK only the serum level of TSA was significantly higher compared to the control group (p < 0.001). When the cSCC and AK groups were compared, significant differences between the serum levels of TSA (p < 0.001), LSA (p < 0.001), ST6GalI (p < 0.001) and NEU3 (p < 0.001) were found. The rate of synthesis of sialoglycoconjugates and their rate of enzymatic degradation, expressed by the ST6GalI/NEU3 ratio, is 1.64 times lower in the cSCC group compared to the control group (p < 0.01) and 1.53 times lower compared to the AK group (p < 0.01). The tumor diameter, depth of invasion, and Ki67 were associated with higher levels of TSA and LSA. These results indicate an aberrant sialylation in cSCC that correlates with tumor aggressiveness.
Highlights
Cutaneous squamous cell carcinoma together with basal cell carcinoma (BCC)represent the most frequent non-melanoma skin cancers [1]
In the actinic keratoses (AK) group, only the total sialic acid (TSA) levels were higher compared to the control group
The rate of synthesis of sialoglycoconjugates and their rate of enzymatic degradation, expressed by the ST6GalI/neuraminidase 3 (NEU3) ratio, is 1.64 times lower in the Cutaneous squamous cell carcinoma (cSCC) group compared to the control group (p < 0.01) and 1.53 times lower compared to the AK group (p < 0.01)
Summary
Cutaneous squamous cell carcinoma (cSCC) together with basal cell carcinoma (BCC)represent the most frequent non-melanoma skin cancers [1]. The most important risk factors associated with cSCC are sun exposure, fair skin phototype, age (mainly diagnosed in middle-aged and older adults), certain beta human papillomavirus (HPV) types [2], and immunosuppression [2,3]. It is well known that cSCC arises on damaged skin, on sites characterized by chronic inflammation such as scars or burns [4]. Sun-exposed keratinocytes produce a wide range of molecules (e.g., inflammatory cytokines, chemokines, growth factors, etc.) that induce increased vascular permeability and the recruitment of immune cells such as neutrophils, macrophages, etc. UV radiation promotes the formation of an inflammatory milieu that contributes to skin carcinogenesis [6]. Chronic inflammation is a cofactor for tumor development and induces local immunosuppression facilitating tumor invasiveness and metastasis.
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