- •Discrepancies between the histologic analyses of cSCC and its precursors make their diagnosis difficult.
- •Protein biomarkers can ameliorate the negative impact of mis- or delayed diagnosis on patient outcome.
- •Proteomics is useful for the identification of new cSCC biomarkers and therapeutic targets.
- •Skin sampling by tape-stripping offers a non-invasive approach to cSCC biomarker discovery.
Cutaneous squamous cell carcinoma (cSCC) and its precursors, actinic keratosis (AK) and Bowen’s disease (BD), are the most common types of keratinocytic skin lesions (KSL) which account for the majority of non-melanoma skin cancer lethality. Currently, clinical and histopathological criteria are used for the diagnosis, classification and therapeutic intervention of KSLs, however discrepancies exist between the clinical presentations and histologic analyses of these lesions, making the diagnosis difficult. The identification of biomarkers as companion diagnostics for accurately stratifying KSL types is required to support the paradigm shift in current cancer care to personalised, precision medicine and ameliorate the negative impact of misdiagnoses or delayed diagnoses on patient outcome. Also, it is essential to elaborate on the poorly defined molecular modifications required for the initiation, development and progression of KSL from normal keratinocytes. By harnessing recent technological advances in molecular profiling techniques, it is anticipated that greater insight into the various combinations of proteomic events or alternative pathways underlying carcinogenesis will be gained. This review will explore recent genomic studies in KSL followed by assessing the feasibility and significance of mass spectrometry-based proteomics profiling as a promising approach to a better understanding of the oncogenic pathways underpinning the formation and progression of KSL lesions and in aiding the identification of novel biomarkers and new therapeutic targets. The development of non-invasive tools such as tape-stripping coupled with proteomic analysis alone or in conjunction with imaging and genomic technologies will complement existing clinical and histopathological parameters, leading to an improvement in patient outcomes.
Abbreviations:AK (actinic keratosis), BD (Bowen’s disease), cSCC (cutaneous squamous cell carcinoma), KSL (keratinocytic skin lesions), SWATH-MS (sequential window acquisition of all theoretical mass spectra)
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- Cancer in Australia 2019.Australian Institute of Health and Welfare, 2019 (2019 Cancer series no.119, Cat. no. CAN 123)
- Non-melanoma skin cancer in Australia.Med. J. Aust. 2012; 197: 565-568
- A.I.o.H.a. Welfare Skin Cancer in Australia. 2016 (Cat. no. CAN 96, in: Canberra, Australia)
- Non-melanoma skin cancer.Lancet. 2010; 375: 673-685
- Chapter 166. Actinic keratosis and Bowen disease.The Color Atlas of Family Medicine. The McGraw-Hill Companies, New York, NY2013 (2e)
- An association between bowen’s disease and internal cancer.Arch. Dermatol. 1961; 84: 623-629
- Precancerous skin lesions.Actas Dermosifiliogr. 2017; 108: 31-41
- The clinical and dermoscopic features of invasive cutaneous squamous cell carcinoma depend on the histopathological grade of differentiation.Br. J. Dermatol. 2015; 172: 1308-1315
- WHO Classification of Skin Tumours.International Agency for Research on Cancer, 2018
- Pseudoepitheliomatous hyperplasia: a review.Am. J. Dermatopathol. 2011; 33: 112-126
- Molecular discrimination of cutaneous squamous cell carcinoma from actinic keratosis and normal skin.Mod. Pathol. 2011; 24: 963-973
- Molecular profiling of cutaneous squamous cell carcinomas and actinic keratoses from organ transplant recipients.BMC Cancer. 2013; 13: 58
- Actinic keratosis is an early in situ squamous cell carcinoma: a proposal for reclassification.Br. J. Dermatol. 2007; 156: 8-12
- Actinic keratosis, transected: what lies beneath?.Am. J. Dermatopathol. 2015; 37: 759-760
- Features causing confusion between basal cell carcinoma and squamous cell carcinoma in clinical diagnosis.Ann. Dermatol. 2018; 30: 64-70
- Predict, prevent and personalize: genomic and proteomic approaches to cardiovascular medicine.Can. J. Cardiol. 2007; 23: 28A-33A
- High burden and pervasive positive selection of somatic mutations in normal human skin.Science. 2015; 348: 880-886
- Eukaryotic genome complexity.Nature Education. 2008; 1: 96
- Comparative analysis of proteome and transcriptome variation in mouse.PLoS Genet. 2011; 7e1001393
- Post-transcriptional regulation across human tissues.PLoS Comput. Biol. 2017; 13e1005535
- Complement factor H: a biomarker for progression of cutaneous squamous cell carcinoma.J. Invest. Dermatol. 2014; 134: 498-506
- Differential expression of degradome components in cutaneous squamous cell carcinomas.Mod. Pathol. 2014; 27: 945-957
- Identification of differentially expressed genes in cutaneous squamous cell carcinoma by microarray expression profiling.Mol. Cancer. 2006; 5: 30
- Microarray analysis of cutaneous squamous cell carcinomas reveals enhanced expression of epidermal differentiation complex genes.Mol. Carcinog. 2010; 49: 619-629
- Biomarkers of human cutaneous squamous cell carcinoma from tissues and cell lines identified by DNA microarrays and qRT-PCR.Biochem. Biophys. Res. Commun. 2003; 306: 1026-1036
- Key differences identified between actinic keratosis and cutaneous squamous cell carcinoma by transcriptome profiling.Br. J. Cancer. 2014; 110: 520-529
- From proteins to proteomes: large scale protein identification by two-dimensional electrophoresis and amino acid analysis.Mar. Biotechnol. 1996; 14: 61-65
- Proteomics in translational cancer research: toward an integrated approach.Cancer Cell. 2003; 3: 9-15
- Expression of desmosomal proteins in squamous cell carcinomas of the skin.J. Cutan. Pathol. 2003; 30: 621-630
- Up-regulation of cyclooxygenase 2 and matrix metalloproteinases-2 and -9 in cutaneous squamous cell carcinoma: active role of inflammation and tissue remodeling in carcinogenesis.Ann. Dermatol. 2013; 25: 145-151
- Epithelial expression of extracellular matrix metalloproteinase inducer/CD147 and matrix metalloproteinase-2 in neoplasms and precursor lesions derived from cutaneous squamous cells: an immunohistochemical study.Pathol. Res. Pract. 2013; 209: 627-634
- Expression of metallothioneins in cutaneous squamous cell carcinoma and actinic keratosis.Pathol. Oncol. Res. 2012; 18: 849-855
- Serpin peptidase inhibitor clade A member 1 (SerpinA1) is a novel biomarker for progression of cutaneous squamous cell carcinoma.Am. J. Pathol. 2011; 179: 1110-1119
- Identification of dysregulated genes in cutaneous squamous cell carcinoma.Oncol. Rep. 2006; 16: 513-519
- Expression of P27, Ki67 and P53 in squamous cell carcinoma, actinic keratosis and Bowen disease.Pak. J. Biol. Sci. 2009; 12: 929-933
- Loss of T-cadherin (CDH13, H-cadherin) expression in cutaneous squamous cell carcinoma.Lab. Invest. 2002; 82: 1023-1029
- Expression of e-cadherin and beta-catenin in cutaneous squamous cell carcinoma and its precursors.Am. J. Dermatopathol. 2004; 26: 372-378
- Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma.Cancer Prev. Res. Phila. (Phila). 2012; 5: 403-413
- A repository of assays to quantify 10,000 human proteins by SWATH-MS.Sci. Data. 2014; 1140031
- Data‐independent acquisition‐based SWATH‐MS for quantitative proteomics: a tutorial.Mol. Syst. Biol. 2018; 14
- Proteomic developments in the analysis of formalin-fixed tissue.Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 2015; 1854: 559-580
- Evaluation of tumor interstitial fluid-extraction methods for proteome analysis: comparison of biopsy elution versus centrifugation.J. Proteome Res. 2019;
- In silico analysis validates proteomic findings of formalin-fixed paraffin embedded cutaneous squamous cell carcinoma tissue.Cancer Genom. Proteom. 2016; 13: 453-465
- Differential proteomic analysis of actinic keratosis, Bowen’s disease and cutaneous squamous cell carcinoma by label-free LC-MS/MS.J. Dermatol. Sci. 2018; 91: 69-78
- Identification of tissue damage, extracellular matrix remodeling and bacterial challenge as common mechanisms associated with high-risk cutaneous squamous cell carcinomas.Matrix Biol. 2018; 66: 1-21
- Data independent acquisition proteomic analysis can discriminate between actinic keratosis, Bowen’s disease, and cutaneous squamous cell carcinoma.J. Invest. Dermatol. 2020; 140 (e11): 212-222
- Tape stripped stratum corneum samples prove to be suitable for comprehensive proteomic investigation of actinic keratosis.Proteomics–Clin. Appl. 2018; 1800084
- Economic analysis of a noninvasive molecular pathologic assay for pigmented skin lesions.JAMA Dermatol. 2018; 154: 1025-1031
- The current role of in vivo reflectance confocal microscopy within the continuum of actinic keratosis and squamous cell carcinoma: a systematic review.Eur. J. Dermatol. 2016; 26: 549-565
- Improved survival prognostication of node-positive malignant melanoma patients utilizing shotgun proteomics guided by histopathological characterization and genomic data.Sci. Rep. (Nature Publisher Group). 2019; 9: 1-14
Dr Ali Azimi is a post-doctoral research fellow with the Department of Dermatology at the University of Sydney, Australia. Dr Azimi, in the past few years, has been involved in utilising cutting-edge mass-spectrometry-based proteomics to resolve the molecular landscape of skin cancers including melanoma and non-melanoma skin cancers. As alternative to biopsy, he has also investigated the use of non-invasive tape-stripping method for proteomic investigation of skin cancers. In collaboration with experts in histopathology, genomics and proteomics, Dr Azimi aims to work towards the introduction of multi-modality research studies in skin cancers to allow a better understanding of the lesions.
Published online: April 07, 2020
Accepted: March 26, 2020
Received in revised form: February 1, 2020
Received: November 17, 2019
© 2020 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.