Significance of circadian genes clock protein in papillary thyroid carcinoma tissues

doi:10.3877/cma.j.issn.1674-0793.2016.03.004

Abstract

Abstract:

Objective

To investigate the protein expression level of CLOCK gene in papillary thyroid carcinoma (PTC) tissues and the relationship between the expression level and pathological features of patients with PTC.

Methods

PTC patients undergoing radical surgery at Affliated PLA No. 97 Hospital from March 2012 to March 2015 were collected. Finally, seventy four cases were enrolled in this study. The expression level of CLOCK protein was analyzed by immunohistochemistry in PTC tissues and the paired adjacent normal thyroid tissues. The relationship between the expression level of CLOCK protein and clinicopathological features were also analyzed.

Results

The positive expression rates of CLOCK protein in PTC tissues and paired adjacent normal tissues were 68.9% (51/74) and 20.3% (15/74), respectively, with significant difference (χ²=35.44, P=0.000). The expression level of CLCOK protein in thyroid cancer was related to lymph node metastasis, diameter of tumor and TNM stage.

Conclusion

The CLOCK protein plays an important role in tumorigenesis, tumor invasion and metastasis.

Key words: Thyroid neoplasms, Carcinoma, papillary, Periodicity, Immunohistochemistry

Chang Han, Dongliang Liu, Feng Zhou, Zhaohui Zhang, Deben Li, Wancheng Niu. Significance of circadian genes clock protein in papillary thyroid carcinoma tissues[J]. Chinese Archives of General Surgery(Electronic Edition), 2016, 10(03): 179-182.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhptwkxwx.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1674-0793.2016.03.004

https://zhptwkxwx.cma-cmc.com.cn/EN/Y2016/V10/I03/179

Figures/Tables 3

References 27

1	Davies L,Morris LG,Haymart M, et al. American Association of Clinical Endocrinologists And American College of Endocrinology Disease State Clinical Review: the increasing incidence of thyroid cancer[J]. Endocr Pract, 2015, 21(6): 686-696.
2	Rossing M,Borup R,Henao R, et al. Down-regulation of microRNAs controlling tumourigenic factors in follicular thyroid carcinoma[J]. J Mol Endocrinol, 2012, 48(1): 11-23.
3	Letsas KP,Frangou-Lazaridis M,Skyrlas A, et al. Transcription factor-mediated proliferation and apoptosis in benign and malig-nant thyroid lesions[J]. Pathol Int, 2005, 55(11): 694-702.
4	Cvejic D,Selemetjev S,Savin S, et al. Apoptosis and proliferation related molecules (Bcl-2, Bax, p53, PCNA) in papillary microcar-cinoma versus papillary carcinoma of the thyroid[J]. Pathology, 2008, 40(5): 475-480.
5	Selemetjev SA,Savin SB,Paunovic IR, et al. Changes in the ex-pression pattern of apoptotic molecules (galectin-3, Bcl-2, Bax, survivin) during progression of thyroid malignancy and their clini-cal significance[J]. Wien Klin Wochenschr, 2015, 127(9): 337-344.
6	Koc M,Aktimur R,Kagan Gokakin A, et al. Expression of FHIT, p16, p53 and EGFR as prognostic markers in thyroid tumors of uncertain malignant potential[J]. J BUON, 2015, 20(2): 567-572.
7	Jiang JL,Tian GL,Chen SJ, et al. Promoter methylation of p16 and RASSF1A genes may contribute to the risk of papillary thy-roid cancer: A meta-analysis[J]. Exp Ther Med, 2015, 10(4): 1549-1555.
8	Wu W,Yang SF,Liu FF, et al. Association between p16 Promoter Methylation and Thyroid Cancer Risk: A Meta-analysis[J]. Asian Pac J Cancer Prev, 2015, 16 (16): 7111-7115.
9	Hoffman AE,Yi CH,Zheng T, et al. CLOCK in breast tumorigen-esis: genetic, epigenetic, and transcriptional profiling analyses[J]. Cancer Res, 2010, 70(4): 1459-1468.
10	Kuo SJ,Chen ST,Yeh KT, et al. Disturbance of circadian gene expression in breast cancer[J]. Virchows Arch, 2009, 454(4): 467-474.
11	Rabstein S,Harth V,Justenhoven C, et al. Polymorphisms in cir-cadian genes, night work and breast cancer: results from the GEN-ICA study[J]. Chronobiol Int, 2014, 31(10): 1115-1122.
12	Zhu Y,Stevens RG,Hoffman AE, et al. Testing the circadian gene hypothesis in prostate cancer: a population-based case-con-trol study[J]. Cancer Res, 2009, 69(24): 9315-9322.
13	Oshima T,Takenoshita S,Akaike M, et al. Expression of circadi-an genes correlates with liver metastasis and outcomes in colorec-tal cancer[J]. Oncol Rep, 2011, 25(5): 1439-1446.
14	Wang Y,Qian R,Sun N, et al. Circadian gene hClock enhances proliferation and inhibits apoptosis of human colorectal carcinoma cells in vitro and in vivo[J]. Mol Med Rep, 2015, 11(6): 4204-4210.
15	Shalev M,Aviram R,Adamovich Y, et al. The PXDLS linear motif regulates circadian rhythmicity through protein-protein in-teractions[J]. Nucleic Acids Res, 2014, 42(19): 11879-11890.
16	Bell-Pedersen D,Cassone VM,Earnest DJ, et al. Circadian rhythms from multiple oscillators: lessons from diverse organisms[J]. Nat Rev Genet, 2005, 6(7): 544-556.
17	Shearman LP,Sriram S,Weaver DR, et al. Interacting molecular loops in the mammalian circadian clock[J]. Science, 2000, 288(5468): 1013-1019.
18	Levi F,Okyar A. Circadian clocks and drug delivery systems: im-pact and opportunities in chronotherapeutics[J]. Expert Opin Drug, 2011, 8(12): 1535-1541.
19	Peek CB,Ramsey KM,Levine DC, et al. Circadian regulation of cellular physiology[J]. Methods Enzymol, 2015, 552: 165-184.
20	Milev NB,Rey G,Valekunja UK, et al. Analysis of the redox os-cillations in the circadian clockwork[J]. Methods Enzymol, 2015, 552: 185-210.
21	Lévi F,Okyar A,Du long S, et al. Circadian timing in cancer treatments[J]. Annu Rev Pharmacol Toxicol, 2010, 50: 377-421.
22	朱晓灵,戴弘季,陈可欣,等. CLOCK基因单核苷酸多态性与乳腺癌易感性的病例对照研究[J].中国肿瘤临床, 2011, 38(3): 121-125.
23	邓香群,张鹏飞,贺印旎.生物钟基因hClock hBmal1在肿瘤中的表达研究[J].中国肿瘤临床, 2011, 38(10): 556-559.
24	Zhou F,He X,Liu H, et al. Functional polymorphisms of circadi-an positive feedback regulation genes and clinical outcome of Chi-nese patients with resected colorectal cancer[J]. Cancer, 2012, 118(4): 937-946.
25	Miller BH,McDearmon EL,Panda S, et al. Circadian and CLOCK-controlled regulation of the mouse transcriptome and cell proliferation[J]. Proc Natl Acad Sci USA, 2007, 104(9): 3342-3477.
26	Yoshida D,Aoki N,Tanaka M, et al. The circadian clock controls fluctuations of colonic cell proliferation during the light/dark cy-cle via feeding behavior in mice[J]. Chronobiol Int, 2015, 32(8): 1145-1155.
27	Mannic T,Meyer P,Triponez F, et al. Circadian clock characteris-tics are altered in human thyroid malignant nodules[J]. J Clin En-docrinol Metab, 2013, 98(11): 4446-4456.

临床病理特征		例数	CLOCK蛋白表达		χ²值	P值
临床病理特征		例数	阴性(-)	阳性(+~+++)	χ²值	P值
年龄（岁）		?	?	?	?	?
?	≤ 45	36	13(36.1)	23(63.9)	0.83	0.255
?	>45	38	10(26.3)	28(73.7)	?	?
性别		?	?	?	?	?
?	男	18	8(44.4)	10(55.6)	1.98	0.133
?	女	56	15(26.8)	41(73.2)	?	?
淋巴结转移		?	?	?	?	?
?	有	16	1(6.2)	15(93.8)	5.88	0.012
?	无	58	22(37.9)	36(62.1)	?	?
直径(cm)		?	?	?	?	?
?	≤2	52	21(40.4)	31(59.6)	7.15	0.028
?	>2～4	20	2(10.0)	18(90.0)	?	?
?	>4	2	0(0)	2(100.0)	?	?
TNM分期		?	?	?	?	?
?	Ⅰ	56	22(39.3)	34(61.7)	7.56	0.023
?	Ⅱ	8	1(12.5)	7(87.5)	?	?
?	Ⅲ	10	0(0)	10(100.0)	?	?

临床病理特征		例数	CLOCK蛋白表达		χ²值	P值
临床病理特征		例数	阴性(-)	阳性(+~+++)	χ²值	P值
年龄（岁）		?	?	?	?	?
?	≤ 45	36	13(36.1)	23(63.9)	0.83	0.255
?	>45	38	10(26.3)	28(73.7)	?	?
性别		?	?	?	?	?
?	男	18	8(44.4)	10(55.6)	1.98	0.133
?	女	56	15(26.8)	41(73.2)	?	?
淋巴结转移		?	?	?	?	?
?	有	16	1(6.2)	15(93.8)	5.88	0.012
?	无	58	22(37.9)	36(62.1)	?	?
直径(cm)		?	?	?	?	?
?	≤2	52	21(40.4)	31(59.6)	7.15	0.028
?	>2～4	20	2(10.0)	18(90.0)	?	?
?	>4	2	0(0)	2(100.0)	?	?
TNM分期		?	?	?	?	?
?	Ⅰ	56	22(39.3)	34(61.7)	7.56	0.023
?	Ⅱ	8	1(12.5)	7(87.5)	?	?
?	Ⅲ	10	0(0)	10(100.0)	?	?

[1]	Zhuangzhuang Wu, Xiaojuan Zhang, Zehong Shi, yao Shi, Shaoling Yuan. Prognostic value of ultrasound combined with mammography and PR and HER-2 status in high-grade and middle-low-grade ductal carcinoma in situ of the breast [J]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2023, 20(06): 631-635.
[2]	Chunying Han, Tingting Wang, Yanyan Li, Jinxia Piao. Current research status on predictors of lymphatic vascular invasion in patients with endometrial carcinoma [J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(04): 403-409.
[3]	Xingchen Liu, Juan Liu, Baobao Wei, Jie Liu, Hui Liu. Correlation analysis of abnormal expression of XIAP and XAF1 with ovarian cancer [J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2023, 19(04): 419-427.
[4]	Yonghao Li, Xuefei Gao, Tiantian Guo, Jin Zhang, Caizhen Zhang, Jing Liu. Advances in the research of mechanisms related to obesity combined with thyroid carcinoma [J]. Chinese Archives of General Surgery(Electronic Edition), 2023, 17(04): 311-315.
[5]	Zhenjian Jiang, Ming Jiang, Dali Huang. The expression and prognostic value of TK1 and Ki67 proteins in differentiated thyroid carcinoma [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(06): 623-626.
[6]	Hui Huang, Xinqiang Zhu. Efficacy and influencing factors of ¹³¹I in the treatment of differentiated thyroid carcinoma under 45 years old [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(06): 627-630.
[7]	Lichao Fan, Jinying Guo, Xin Chen. The significance of detection of wild-type RET and RET/PTC fusion gene for lymph node dissection in the central region of papillary thyroid carcinoma [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(06): 631-635.
[8]	Cheng Xu, Lulu Wang, Shaohua Wang. Application of eluent thyroglobulin in metastatic lymph nodes of thyroid papillary carcinoma [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(06): 701-704.
[9]	Yao Chen, Boqun Xu, Zhihui Gao. Efficacy and safety of modified intermediate upper approach radical resection in the treatment of thyroid cancer [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(06): 619-622.
[10]	Zhanbin Cui, Junli Qiao, Lili Zhang, Mingqiang Han. Correlation between urinary iodine levels and stratified risk of recurrence in patients with papillary thyroid cancer after surgery [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(06): 615-618.
[11]	Yutao Yuan, Jinlin Xing, Kefei Xie, Kai Yin. Correlation between CT findings and BRAF^V600E gene mutation and central lymph node metastasis in papillary thyroid carcinoma [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(06): 611-614.
[12]	Yi Wang, Sizhe Xu, Zhangxia Ren. Effect of endoscopic unilateral thyroid lobectomy via thoracic breast approach and open surgery on postoperative recovery in patients with differentiated thyroid cancer [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(05): 542-545.
[13]	Rong Zhang, Hongzhen Qin, Xiaodong Yang, Shuang Liu, Mingfeng Liu, Xiutang Cao. Clinical application and observation of postoperative rehabilitation exercise of patients with differentiated thyroid cancer [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2023, 17(04): 439-442.
[14]	Ruixue Yue, Lingxin Kong, Xin Hao, Jinqiang Yang, Meng Han, Guozhong Cui, Jianjun Wang, Zhisheng Zhang, Fanting Kong, Wei Zhang, Wenbo He, Xianqiao Li, Xinping Zhou, Donghong Xu, Chongzhu Hu. HER2 protein expression levels predict efficacy of neoadjuvant therapy in breast cancer: A real-world study [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(07): 765-770.
[15]	Wenbo Niu, Fengpeng Wu, Yueping Liu, Chaoxi Zhou, Juan Zhang, Xuhua Hu, Baokun Li, Gueying Wang. Neoadjuvant chemoradiotherapy for treatment of locally advanced rectal cancer: Efficacy and tumor immune microenvironment changes [J]. Chinese Journal of Clinicians(Electronic Edition), 2023, 17(05): 519-523.

Please choose a citation manager

Content to export