Original tumour suppressor gene polycystic kidney and hepatic disease 1‑like 1 is associated with thyroid cancer cell progression

Zheng,Chen; Quan,Ruida; Xia,Er‑Jie; Bhandari,Adheesh; Zhang,Xiaohua

doi:10.3892/ol.2019.10632

Original tumour suppressor gene polycystic kidney and hepatic disease 1‑like 1 is associated with thyroid cancer cell progression

Authors:
- Chen Zheng
- Ruida Quan
- Er‑Jie Xia
- Adheesh Bhandari
- Xiaohua Zhang
View Affiliations

Affiliations: Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
Published online on: July 18, 2019 https://doi.org/10.3892/ol.2019.10632
Pages: 3227-3235
Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

In recent decades, thyroid cancer (TC) has become one of the most common endocrine malignancies. Next‑generation sequencing of paired TC and adjacent healthy thyroid tissues demonstrated that polycystic kidney and hepatic disease 1‑like 1 (PKHD1L1) may serve as a tumour suppressor gene in thyroid cancer. However, the function of PKHD1L1 in thyroid cancer is still unknown. To validate the results of whole‑transcriptome resequencing, the expression levels of PKHD1L1 were evaluated in 58 pairs of papillary thyroid cancer (PTC) tissue samples and three thyroid cancer cell lines. In addition, The Cancer Genome Atlas (TCGA) data were used to analyse the relationship between PKHD1L1 and patient clinicopathological features. Cell Counting Kit‑8, colony formation, migration and invasion assays were performed to assess the effects of PKHD1L1 knockdown in three TC cell lines. PKHD1L1 expression was significantly lower in thyroid carcinoma compared with that in matched normal tissue, and this result was consistent with that in TCGA cohort. TCGA data demonstrated that PKHD1L1 downregulation was associated with a number of aggressive clinicopathological features, such as histological type, lymph node metastasis (LNM), distant metastasis, tumour size and clinical stage. Logistic regression analysis of data from patients with PTC revealed that PKHD1L1 expression, histological type, age and tumour size were independent high‑risk factors for LNM. The PKHD1L1 biological function was investigated in the three TC cell lines: TPC‑1, KTC1 and BCPAP. A loss of function experiment demonstrated that PKHD1L1 knockdown promoted cell proliferation, colony formation and cell invasion in TC cell lines. In conclusion, PKHD1L1 may be a tumour suppressor gene associated with PC, and may be a potential therapeutic target in the future.

View Figures

View References

1	Burns WR and Zeiger MA: Differentiated thyroid cancer. Semin Oncol. 37:557–566. 2010. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
3	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
4	Pellegriti G, Frasca F, Regalbuto C, Squatrito S and Vigneri R: Worldwide increasing incidence of thyroid cancer: Update on epidemiology and risk factors. J Cancer Epidemiol. 2013:9652122013. View Article : Google Scholar : PubMed/NCBI
5	Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM and Matrisian LM: Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 74:2913–2921. 2014. View Article : Google Scholar : PubMed/NCBI
6	Morris LG, Tuttle RM and Davies L: Changing trends in the incidence of thyroid cancer in the United States. JAMA Otolaryngol Head Neck Surg. 142:709–711. 2016. View Article : Google Scholar : PubMed/NCBI
7	La Vecchia C, Malvezzi M, Bosetti C, Garavello W, Bertuccio P, Levi F and Negri E: Thyroid cancer mortality and incidence: A global overview. Int J Cancer. 136:2187–2195. 2015. View Article : Google Scholar : PubMed/NCBI
8	Leboulleux S, Rubino C, Baudin E, Caillou B, Hartl DM, Bidart JM, Travagli JP and Schlumberger M: Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis. J Clin Endocrinol Metab. 90:5723–5729. 2005. View Article : Google Scholar : PubMed/NCBI
9	Parangi S and Suh H: The role of genetic markers in the evaluation and management of thyroid nodules. Surg Clin North Am. 94:515–528. 2014. View Article : Google Scholar : PubMed/NCBI
10	Xing M: Molecular pathogenesis and mechanisms of thyroid cancer. Nat Rev Cancer. 13:184–199. 2013. View Article : Google Scholar : PubMed/NCBI
11	Xing M: Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer. Thyroid. 20:697–706. 2010. View Article : Google Scholar : PubMed/NCBI
12	Xing M: BRAF mutation in thyroid cancer. Endocr Relat Cancer. 12:245–262. 2005. View Article : Google Scholar : PubMed/NCBI
13	Elisei R, Viola D, Torregrossa L, Giannini R, Romei C, Ugolini C, Molinaro E, Agate L, Biagini A, Lupi C, et al: The BRAF(V600E) mutation is an independent, poor prognostic factor for the outcome of patients with low-risk intrathyroid papillary thyroid carcinoma: Single-institution results from a large cohort study. J Clin Endocrinol Metab. 97:4390–4398. 2012. View Article : Google Scholar : PubMed/NCBI
14	Tavares C, Melo M, Cameselle-Teijeiro JM, Soares P and Sobrinho-Simões M: ENDOCRINE TUMOURS: Genetic predictors of thyroid cancer outcome. Eur J Endocrinol. 174:R117–R126. 2016. View Article : Google Scholar : PubMed/NCBI
15	Gustafson S, Zbuk KM, Scacheri C and Eng C: Cowden syndrome. Semin Oncol. 34:428–434. 2007. View Article : Google Scholar : PubMed/NCBI
16	Morita N, Ikeda Y and Takami H: Clinical significance of p53 protein expression in papillary thyroid carcinoma. World J Surg. 32:2617–2622. 2008. View Article : Google Scholar : PubMed/NCBI
17	Liu X, Bishop J, Shan Y, Pai S, Liu D, Murugan AK, Sun H, El-Naggar AK and Xing M: Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocr Relat Cancer. 20:603–610. 2013. View Article : Google Scholar : PubMed/NCBI
18	Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, et al: Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proc Natl Acad Sci USA. 99:16899–16903. 2002. View Article : Google Scholar : PubMed/NCBI
19	Lian PW, Fu YL, Li A, Dai BZ, Ding ZW, Li L and Wu GQ: Preparation and characterization of a polyclonal antibody against human Fibrocystin-L. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 27:78–81. 2011.(In Chinese). PubMed/NCBI
20	Hogan MC, Griffin MD, Rossetti S, Torres VE, Ward CJ and Harris PC: PKHDL1, a homolog of the autosomal recessive polycystic kidney disease gene, encodes a receptor with inducible T lymphocyte expression. Hum Mol Genet. 12:685–698. 2003. View Article : Google Scholar : PubMed/NCBI
21	Erdman VV, Karimov DD, Nasibullin TR, Timasheva IR, Tuktarova IA and Mustafina OE: Role of PLAT, PKHD1L1, STK38L and TEAD1 genes Alu-polymorphism for longevity. Adv Gerontol. 29:709–716. 2016.(In Russian). PubMed/NCBI
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
23	Edge SB and Compton CC: The American Joint Committee on cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
24	Mustafa M, Kuwert T, Weber K, Knesewitsch P, Negele T, Haug A, Linke R, Bartenstein P and Schmidt D: Regional lymph node involvement in T1 papillary thyroid carcinoma: A bicentric prospective SPECT/CT study. Eur J Nucl Med Mol Imaging. 37:1462–1466. 2010. View Article : Google Scholar : PubMed/NCBI
25	Schneider DF and Chen H: New developments in the diagnosis and treatment of thyroid cancer. CA Cancer J Clin. 63:374–394. 2013. View Article : Google Scholar : PubMed/NCBI
26	Cho SY, Lee TH, Ku YH, Kim HI, Lee GH and Kim MJ: Central lymph node metastasis in papillary thyroid microcarcinoma can be stratified according to the number, the size of metastatic foci, and the presence of desmoplasia. Surgery. 157:111–118. 2015. View Article : Google Scholar : PubMed/NCBI
27	Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Kuma K and Miyauchi A: Ultrasonographically and anatomopathologically detectable node metastases in the lateral compartment as indicators of worse relapse-free survival in patients with papillary thyroid carcinoma. World J Surg. 29:917–920. 2005. View Article : Google Scholar : PubMed/NCBI
28	Lee YM, Sung TY, Kim WB, Chung KW, Yoon JH and Hong SJ: Risk factors for recurrence in patients with papillary thyroid carcinoma undergoing modified radical neck dissection. Br J Surg. 103:1020–1025. 2016. View Article : Google Scholar : PubMed/NCBI
29	Sancho JJ, Lennard TW, Paunovic I, Triponez F and Sitges-Serra A: Prophylactic central neck disection in papillary thyroid cancer: A consensus report of the European society of endocrine surgeons (ESES). Langenbecks Arch Surg. 399:155–163. 2014. View Article : Google Scholar : PubMed/NCBI
30	Comuzzie AG, Cole SA, Laston SL, Voruganti VS, Haack K, Gibbs RA and Butte NF: Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PLoS One. 7:e519542012. View Article : Google Scholar : PubMed/NCBI
31	Wang QX, Chen ED, Cai YF, Li Q, Jin YX, Jin WX, Wang YH, Zheng ZC, Xue L, Wang OC and Zhang XH: A panel of four genes accurately differentiates benign from malignant thyroid nodules. J Exp Clin Cancer Res. 35:1692016. View Article : Google Scholar : PubMed/NCBI