Related mechanism between skin aging and occurrence of cutaneous squamous cell carcinoma: a high-throughput proteomics-based analysis_West China Medical Journal

Authors：

ZHANG Shiwei ,  CHEN Junjie

Department of Burn and Plastic Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R China;

Corresponding author：

CHEN Junjie, Email: cjjemail@163.com

Keywords：

Cutaneous squamous cell carcinoma; aging; proteomics; extracellular matrix

DOI：

10.7507/1002-0179.202310219

Video：

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Objective To investigate the proteomic changes among normal skin tissues in young and elderly people and cutaneous squamous cell carcinoma (cSCC) tissues in elderly patients with cSCC, find proteins associated with skin aging and cSCC, and provide a new basis for target screening for cSCC therapy. Methods Five cSCC tissue samples from 5 elderly patients with cSCC and 10 normal skin tissue samples from 5 young and 5 elderly people removed during surgery between January 2019 and December 2020 in West China Hospital of Sichuan University were selected. The differences in tissue morphology and structure were observed by hematoxylin-eosin staining, and the whole protein group was qualitatively and quantitatively analyzed by pressure cycle technique. Results With aging, the structure of skin tissues underwent corresponding changes, including thinning of the skin, increased collagen fiber density, and more organized arrangement. Compared to normal skin tissue, cSCC tissue exhibited epithelial cell dysplasia, atypical mitoses, nest-like distribution of cancer cells, infiltration of inflammatory cells, and formation of keratin pearls. Proteomic analysis identified 3008 specific proteins, and there were 37 proteins with common differential expression. Further screening of databases identified 8 proteins derived from the extracellular matrix, primarily involved in morphological structure formation, tensile strength, interaction with platelet-derived growth factors and receptors, collagen degradation metabolism, and cell adhesion. Conclusions Aging leads to changes in skin structure. The changes of tissue structure caused by aging lead to the weakening of skin barrier function. At the same time, aging leads to the down-regulated expression of protein with the function of inhibiting tumor progression and the up-regulated expression of protein with the function of promoting tumor progression in extracellular matrix. These changes may affect the occurrence and development of cSCC by affecting the regulation mechanism of tumor extracellular microenvironment.

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1. Levi N, Papismadov N, Solomonov I, et al. The ECM path of senescence in aging: components and modifiers. FEBS J, 2020, 287(13): 2636-2646.
2. Marozzi M, Parnigoni A, Negri A, et al. Inflammation, extracellular matrix remodeling, and proteostasis in tumor microenvironment. Int J Mol Sci, 2021, 22(15): 8102.
3. Dyussenbayev A. The main periods of human life. Glob J Hum Soc Sci, 2017, 17(7): 32-36.
4. Guo T, Kouvonen P, Koh CC, et al. Rapid mass spectrometric conversion of tissue biopsy samples into permanent quantitative digital proteome maps. Nat Med, 2015, 21(4): 407-413.
5. Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol, 2018, 78(2): 237-247.
6. Franco AC, Aveleira C, Cavadas C. Skin senescence: mechanisms and impact on whole-body aging. Trends Mol Med, 2022, 28(2): 97-109.
7. Waller JM, Maibach HI. Age and skin structure and function, a quantitative approach (I): blood flow, pH, thickness, and ultrasound echogenicity. Skin Res Technol, 2005, 11(4): 221-235.
8. Sauermann K, Jaspers S, Koop U, et al. Topically applied vitamin C increases the density of dermal papillae in aged human skin. BMC Dermatol, 2004, 4(1): 13.
9. Tobin DJ. Introduction to skin aging. J Tissue Viability, 2017, 26(1): 37-46.
10. Stratigos AJ, Garbe C, Dessinioti C, et al. European interdisciplinary guideline on invasive squamous cell carcinoma of the skin: Part 1. epidemiology, diagnostics and prevention. Eur J Cancer, 2020, 128: 60-82.
11. Baghban R, Roshangar L, Jahanban-Esfahlan R, et al. Tumor microenvironment complexity and therapeutic implications at a glance. Cell Commun Signal, 2020, 18(1): 59.
12. Huang J, Zhang L, Wan D, et al. Extracellular matrix and its therapeutic potential for cancer treatment. Signal Transduct Target Ther, 2021, 6(1): 153.
13. Hu SM, Li F, Yu HM, et al. The mimecan gene expressed in human pituitary and regulated by pituitary transcription factor-1 as a marker for diagnosing pituitary tumors. J Clin Endocrinol Metab, 2005, 90(12): 6657-6664.
14. Fasehee H, Fakhraee M, Davoudi S, et al. Cancer biomarkers in atherosclerotic plaque: evidenced from structural and proteomic analyses. Biochem Biophys Res Commun, 2019, 509(3): 687-693.
15. Gopinath P, Natarajan A, Sathyanarayanan A, et al. The multifaceted role of matricellular proteins in health and cancer, as biomarkers and therapeutic targets. Gene, 2022, 815: 146137.
16. Moriggi M, Giussani M, Torretta E, et al. ECM remodeling in breast cancer with different grade: contribution of 2D-DIGE proteomics. Proteomics, 2018, 18(24): e1800278.
17. Wang Y, Wang L, Wen X, et al. NF-κB signaling in skin aging. Mech Ageing Dev, 2019, 184: 111160.
18. Chiavarina B, Ronca R, Otaka Y, et al. Fibroblast-derived prolargin is a tumor suppressor in hepatocellular carcinoma. Oncogene, 2022, 41(10): 1410-1420.
19. Gambichler T, Elfering J, Meyer T, et al. Protein expression of prognostic genes in primary melanoma and benign nevi. J Cancer Res Clin Oncol, 2022, 148(10): 2673-2680.
20. Long R, Liu Z, Li J, et al. COL6A6 interacted with P4HA3 to suppress the growth and metastasis of pituitary adenoma via blocking PI3K-Akt pathway. Aging (Albany NY), 2019, 11(20): 8845-8859.
21. Qiao H, Feng Y, Tang H. COL6A6 inhibits the proliferation and metastasis of non-small cell lung cancer through the JAK signalling pathway. Transl Cancer Res, 2021, 10(10): 4514-4522.
22. Ganapathi MK, Jones WD, Sehouli J, et al. Expression profile of COL2A1 and the pseudogene SLC6A10P predicts tumor recurrence in high-grade serous ovarian cancer. Int J Cancer, 2016, 138(3): 679-688.
23. Xie W, Huang P, Wu B, et al. Clinical significance of LOXL4 expression and features of LOXL4-associated protein-protein interaction network in esophageal squamous cell carcinoma. Amino Acids, 2019, 51(5): 813-828.
24. de Serres F, Blanco I. Role of alpha-1 antitrypsin in human health and disease. J Intern Med, 2014, 276(4): 311-335.
25. McElvaney OF, Fraughen DD, McElvaney OJ, et al. Alpha-1 antitrypsin deficiency: current therapy and emerging targets. Expert Rev Respir Med, 2023, 17(3): 191-202.
26. Chen D, Yoo BK, Santhekadur PK, et al. Insulin-like growth factor-binding protein-7 functions as a potential tumor suppressor in hepatocellular carcinoma. Clin Cancer Res, 2011, 17(21): 6693-6701.
27. Pen A, Durocher Y, Slinn J, et al. Insulin-like growth factor binding protein 7 exhibits tumor suppressive and vessel stabilization properties in U87MG and T98G glioblastoma cell lines. Cancer Biol Ther, 2011, 12(7): 634-646.
28. Leto G, Tumminello FM, Crescimanno M, et al. Cathepsin D expression levels in nongynecological solid tumors: clinical and therapeutic implications. Clin Exp Metastasis, 2004, 21(2): 91-106.
29. Tsukuba T, Okamoto K, Yasuda Y, et al. New functional aspects of cathepsin D and cathepsin E. Mol Cells, 2000, 10(6): 601-611.
30. Dian D, Heublein S, Wiest I, et al. Significance of the tumor protease cathepsin D for the biology of breast cancer. Histol Histopathol, 2014, 29(4): 433-438.
31. Dong Y, Zhong J, Dong L. The role of decorin in autoimmune and inflammatory diseases. J Immunol Res, 2022, 2022: 1283383.
32. Ji C, Liu H, Xiang M, et al. Deregulation of decorin and FHL1 are associated with esophageal squamous cell carcinoma progression and poor prognosis. Int J Clin Exp Med, 2015, 8(11): 20965-20970.
33. Kasamatsu A, Uzawa K, Minakawa Y, et al. Decorin in human oral cancer: a promising predictive biomarker of S-1 neoadjuvant chemosensitivity. Biochem Biophys Res Commun, 2015, 457(1): 71-76.

West China Medical Journal

Latest ArticlesRelated mechanism between skin aging and occurrence of cutaneous squamous cell carcinoma: a high-throughput proteomics-based analysis

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