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Tumor keratin 15 expression links with less extent of invasion and better prognosis in papillary thyroid cancer patients receiving tumor resection

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Abstract

Objective

Keratin 15 (KRT15) is identified as a useful biomarker in several solid tumors, while its clinical role in papillary thyroid cancer (PTC) remains unknown. Herein, this study is intended to explore the correlation of tumor KRT15 with clinical features and survival in PTC patients who received tumor resection.

Methods

This study retrospectively screened 350 PTC patients who received tumor resection and 50 thyroid benign lesions (TBL) patients. KRT15 in formalin-fixed paraffin-embedded lesion specimens of all subjects was detected by immunohistochemistry (IHC).

Results

KRT15 was reduced in PTC patients compared to TBL patients (P < 0.001). Furthermore, KRT15 was negatively associated with tumor size (P = 0.017), extrathyroidal invasion (P = 0.007), pathological tumor (pT) stage (P < 0.001), and postoperative radioiodine application (P = 0.008) in PTC patients. Regarding prognostic value, high KRT15 (cut-off by an IHC value of 3) is linked with prolonged accumulating disease-free survival (DFS) (P = 0.008) and overall survival (OS) (P = 0.008) in PTC patients. Also, the multivariate Cox regression model showed that high KRT15 (vs. low) was an independent factor for longer DFS (hazard ratio = 0.433, P = 0.049), but not for OS (P > 0.050) in PTC patients. Subgroup analyses revealed that KRT15 possessed a better prognostic value in PTC patients with age ≥ 55 years, tumor size > 4 cm, pathological node stage 1, or pathological tumor-node-metastasis stage ≤ 2 (all P < 0.050).

Conclusion

Increased tumor KRT15 associates with a lower invasive degree, prolonged DFS, and OS, revealing its prognostic utility in PTC patients undergoing tumor resection.

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References

  1. Miranda-Filho A, Lortet-Tieulent J, Bray F et al (2021) Thyroid cancer incidence trends by histology in 25 countries: a population-based study. Lancet Diabetes Endocrinol 9(4):225–234. https://doi.org/10.1016/S2213-8587(21)00027-9

    Article  PubMed  Google Scholar 

  2. Seib CD, Sosa JA (2019) Evolving understanding of the epidemiology of thyroid cancer. Endocrinol Metab Clin North Am 48(1):23–35. https://doi.org/10.1016/j.ecl.2018.10.002

    Article  PubMed  Google Scholar 

  3. Filetti S, Durante C, Hartl D et al (2019) Thyroid cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-updagger. Ann Oncol 30(12):1856–1883. https://doi.org/10.1093/annonc/mdz400

  4. Haddad RI, Bischoff L, Ball D et al (2022) Thyroid carcinoma, version 2.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 20(8):925–951. https://doi.org/10.6004/jnccn.2022.0040

  5. Lee J, Lee SG, Kim K et al (2019) Clinical value of lymph node ratio integration with the 8(th) edition of the UICC TNM classification and 2015 ATA risk stratification systems for recurrence prediction in papillary thyroid cancer. Sci Rep 9(1):13361. https://doi.org/10.1038/s41598-019-50069-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rui ZY, Liu Y, Zheng W et al (2021) A retrospective study of the risk factors and the prognosis in patients with papillary thyroid carcinoma depending on the number of lymph node metastasis. Clin Exp Med 21(2):277–286. https://doi.org/10.1007/s10238-020-00675-8

    Article  PubMed  Google Scholar 

  7. Wagner K, Abraham E, Tran B et al (2020) Lymphovascular invasion and risk of recurrence in papillary thyroid carcinoma. ANZ J Surg 90(9):1727–1732. https://doi.org/10.1111/ans.16202

    Article  PubMed  Google Scholar 

  8. Ulisse S, Baldini E, Lauro A et al (2021) Papillary thyroid cancer prognosis: an evolving field. Cancers (Basel) 13(21). https://doi.org/10.3390/cancers13215567

  9. Waseem A, Dogan B, Tidman N et al (1999) Keratin 15 expression in stratified epithelia: downregulation in activated keratinocytes. J Invest Dermatol 112(3):362–369. https://doi.org/10.1046/j.1523-1747.1999.00535.x

    Article  CAS  PubMed  Google Scholar 

  10. Chen W, Miao C (2022) KRT15 promotes colorectal cancer cell migration and invasion through beta-catenin/MMP-7 signaling pathway. Med Oncol 39(5):68. https://doi.org/10.1007/s12032-021-01619-2

    Article  CAS  PubMed  Google Scholar 

  11. Giroux V, Stephan J, Chatterji P et al (2018) Mouse intestinal Krt15+ Crypt cells are radio-resistant and tumor initiating. Stem Cell Reports 10(6):1947–1958. https://doi.org/10.1016/j.stemcr.2018.04.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tai G, Ranjzad P, Marriage F et al (2013) Cytokeratin 15 marks basal epithelia in developing ureters and is upregulated in a subset of urothelial cell carcinomas. PLoS One 8(11):e81167. https://doi.org/10.1371/journal.pone.0081167

  13. Yang H, Li A, Li A et al (2022) Upregulated keratin 15 links to the occurrence of lymphovascular invasion, stromal cervical invasion as well as unfavorable survival profile in endometrial cancer patients. Medicine (Baltimore) 101(29):e29686. https://doi.org/10.1097/MD.0000000000029686

  14. Rao X, Wang J, Song HM et al (2020) KRT15 overexpression predicts poor prognosis in colorectal cancer. Neoplasma 67(2):410–414. https://doi.org/10.4149/neo_2019_190531N475

    Article  CAS  PubMed  Google Scholar 

  15. Zhong P, Shu R, Wu H et al (2021) Low KRT15 expression is associated with poor prognosis in patients with breast invasive carcinoma. Exp Ther Med 21(4):305. https://doi.org/10.3892/etm.2021.9736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zhang W, Chen P, Li Z et al (2023) Clinical implication of keratin-15 quantification for renal cell carcinoma management: its dysregulation and association with clinicopathologic characteristics and prognostication. Tohoku J Exp Med. https://doi.org/10.1620/tjem.2023.J017

    Article  PubMed  Google Scholar 

  17. Schmid KW, Synoracki S, Dralle H, Wittekind C (2019) Proposal for an extended pTNM classification of thyroid carcinoma : commentary on deficits of the 8th edition of the TNM classification. Pathologe 40(Suppl 1):18–24. https://doi.org/10.1007/s00292-018-0418-x

  18. Peng W, Li W, Zhang X et al (2022) The intercorrelation among CCT6A, CDC20, CCNB1, and PLK1 expressions and their clinical value in papillary thyroid carcinoma prognostication. J Clin Lab Anal 36(9):e24609. https://doi.org/10.1002/jcla.24609

  19. Makki FM, Taylor SM, Shahnavaz A et al (2013) Serum biomarkers of papillary thyroid cancer. J Otolaryngol Head Neck Surg 42(1):16. https://doi.org/10.1186/1916-0216-42-16

    Article  PubMed  PubMed Central  Google Scholar 

  20. Viana AOR, Goncalves Filho J, Francisco ALN et al (2020) Ki-67 and CK-19 are predictors of locoregional recurrence in papillary thyroid carcinoma. Acta Otorhinolaryngol Ital 40(3):190–197. https://doi.org/10.14639/0392-100X-N0311

  21. Abouhashem NS, Talaat SM (2017) Diagnostic utility of CK19 and CD56 in the differentiation of thyroid papillary carcinoma from its mimics. Pathol Res Pract 213(5):509–517. https://doi.org/10.1016/j.prp.2017.01.017

    Article  CAS  PubMed  Google Scholar 

  22. Abbas O, Richards JE, Yaar R, Mahalingam M (2011) Stem cell markers (cytokeratin 15, cytokeratin 19 and p63) in in situ and invasive cutaneous epithelial lesions. Mod Pathol 24(1):90–97. https://doi.org/10.1038/modpathol.2010.180

    Article  CAS  PubMed  Google Scholar 

  23. Zhang C, Liang Y, Ma MH et al (2019) KRT15, INHBA, MATN3, and AGT are aberrantly methylated and differentially expressed in gastric cancer and associated with prognosis. Pathol Res Pract 215(5):893–899. https://doi.org/10.1016/j.prp.2019.01.034

    Article  CAS  PubMed  Google Scholar 

  24. Ciappuccini R, Heutte N, Lasne-Cardon A et al (2020) Tumor burden of persistent disease in patients with differentiated thyroid cancer: correlation with postoperative risk-stratification and impact on outcome. BMC Cancer 20(1):765. https://doi.org/10.1186/s12885-020-07269-3

    Article  PubMed  PubMed Central  Google Scholar 

  25. Coca-Pelaz A, Shah JP, Hernandez-Prera JC et al (2020) Papillary thyroid cancer-aggressive variants and impact on management: a narrative review. Adv Ther 37(7):3112–3128. https://doi.org/10.1007/s12325-020-01391-1

    Article  PubMed  PubMed Central  Google Scholar 

  26. Lin JB, Feng Z, Qiu ML et al (2020) KRT 15 as a prognostic biomarker is highly expressed in esophageal carcinoma. Future Oncol 16(25):1903–1909. https://doi.org/10.2217/fon-2019-0603

    Article  CAS  PubMed  Google Scholar 

  27. Khanom R, Sakamoto K, Pal SK et al (2012) Expression of basal cell keratin 15 and keratin 19 in oral squamous neoplasms represents diverse pathophysiologies. Histol Histopathol 27(7):949–959. https://doi.org/10.14670/HH-27.949

  28. Evangelista MT, North JP (2015) Comparative analysis of cytokeratin 15, TDAG51, cytokeratin 20 and androgen receptor in sclerosing adnexal neoplasms and variants of basal cell carcinoma. J Cutan Pathol 42(11):824–831. https://doi.org/10.1111/cup.12546

    Article  PubMed  Google Scholar 

  29. Kim Y, Roh JL, Song DE et al (2020) Risk factors for posttreatment recurrence in patients with intermediate-risk papillary thyroid carcinoma. Am J Surg 220(3):642–647. https://doi.org/10.1016/j.amjsurg.2020.01.049

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Head and Neck Surgery, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Harbin, 150080, China

    Xianguang Yang, Zhonghao Liu, Xueqian Wang, Zheng Han, Cong Zhang & Lunhua Guo

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Correspondence to Lunhua Guo.

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Yang, X., Liu, Z., Wang, X. et al. Tumor keratin 15 expression links with less extent of invasion and better prognosis in papillary thyroid cancer patients receiving tumor resection. Ir J Med Sci 193, 9–15 (2024). https://doi.org/10.1007/s11845-023-03413-7

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  • DOI: https://doi.org/10.1007/s11845-023-03413-7

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