Dissertations
Roles of Novel Biomarkers in Progression of Cutaneous Squamous Cell Carcinoma
Mehdi Farshchian , MD Department of Dermatology and Venereology , University of Turku and Turku University , Turku , Finland Hospital , Finland . E-mail : mehfar @ utu . fi
Mehdi Farshchian defended his thesis in University of Turku , Finland on August 7 th , 2015 . The custos and the supervisor of the thesis was Professor Veli-Matti Kähäri and the opponent was Professor Eugene Healy from University of Southampton , UK . The thesis is available at : https :// www . doria . fi / handle / 10024 / 111863
The incidence of cutaneous squamous cell carcinoma ( cSCC ) is increasing worldwide due to lifestyle changes such as recreational exposure to sunlight and the aging of the population . The thesis project was planned to identify novel biomarkers for the growth and progression of cSCC . As the most common metastatic form of the cutaneous malignancy , cSCC has a risk of metastasis and invasion if left untreated . In addition , early detection of the tumour is invaluable in the patients with high risk of cSCC , such as immunosuppressed patients . Furthermore , these biomarkers could serve as therapeutic targets particularly in the patients with metastatic and unresectable lesions . The thesis project was mainly established on the extensive gene expression profiling of the primary and metastatic cSCC cells and normal human epidermal keratinocytes ( NHEKs ).
We found that SERPINA1 , which codes for alpha-1-antitrypsin , is upregulated in cSCC cells compared to NHEKs . Immunohistochemistry analysis of the tissue microarrays , consisting of a large panel of normal skin , actinic keratosis ( AK ), cSCC in situ ( cSCCIS ), sporadic cSCC and recessive dystrophic epidermolysis bullosa ( RDEB ) -associated cSCC , revealed a strong expression of SerpinA1 in sporadic cSCC and RDEB-associated SCC . In addition , the expression of SerpinA1 is correlated with the malignant transformation of epidermal keratinocytes in cell culture and the progression of cSCC in vivo .
Given the fact that the role that Eph receptors and ephrin ligands play in different malignancies is complex , part of this thesis work was focused on investigating the role of Eph / ephrin in cSCC . EPHB2 gained our attention in this thesis project , because it revealed a significant upregulation in cSCC cells compared to NHEKs both in microarray-based gene expression profiling and next generation sequencing . Further analysis by quantitative real-time PCR verified markedly overexpression of EPHB2 in cSCC cells and tumours . EphB2 staining was significantly stronger in cSCC and cSCCIS compared to AK and normal skin . Furthermore , EphB2 knockdown inhibited growth of the cSCC in a xenograft model . EphB2 knockdown
Fig . 1 . Mehdi Farshchian ( middle ) defended his PhD thesis on biomarkers of squamous cell carcinoma in Turku , Finland on August 7 th 2015 . The opponent was Professor Eugene Healy from Southampton ( right ) and Professor Veli-Matti Kähäri ( left ) was the supervisor of the thesis .
was shown to inhibit proliferation , migration and invasion of cSCC cell lines . Inhibition of invasion-related matrix metalloproteinases ( MMPs ), MMP-1 and MMP-13 as a result of EphB2 knockdown could be the possible mechanism for the inhibition of the invasion of cSCC cells .
Because inflammation is involved in the development of cSCC , as the third part of the thesis project , the role of absent in melanoma 2 ( AIM2 ) in the progression of cSCC was analyzed . Overexpression of AIM2 was observed in cSCC cell lines and tumours when compared with NHEKs and normal skin , respectively . Tumour cell-specific AIM2 expression was detected in sporadic cSCC and cSCC of the organ transplant recipients . In addition , AIM2 knockdown was shown to inhibit proliferation and invasion of cSCC cell lines and delay the growth and vascularization of cSCC tumours in a xenograft model , which
94 Forum for Nord Derm Ven 2016 , Vol . 21 , No . 4