Aberrant Expression of Per1, Per2 and Per3 and Their Prognostic Relevance in Non-small Cell Lung Cancer

Overview

Journal Int J Clin Exp Pathol

Specialty Pathology

Date 2015 Jan 1

PMID 25550826

Citations 38

Authors

Bin Liu

Ke Xu

Yufeng Jiang

Xiaoling Li

Affiliations

Soon will be listed here.

Abstract

The objective of the current study was to investigate the expression pattern and clinicopathological significance of Period1 (Per1), Period2 (Per2) and Period3 (Per3) in patients with non-small cell lung cancer (NSCLC). In 130 archived NSCLC tissues, the positive rate of Per1 (86/130, 66.2%), Per2 (77/130, 59.2%) and Per3 (82/130, 63.1%) were reduced in human lung cancer samples compared with adjacent normal lung tissues (Per1, 119/130, 91.5%; Per2, 115/130, 88.5%; Per3, 121/130, 93.1%), as measured by immunohistochemical staining. Loss of Per1 was correlated with poor differentiation (P < 0.001), tumor status (P=0.04), high p-TNM stage (P < 0.001) and lymph node metastasis (P=0.045). The similar tendencies were also found in the correlation of the expression of Per2 and Per3 with clinicopathological factors. In addition, a significant correlation was found between Per1 and Per2 (P < 0.001) in 130 cases of NSCLC. Similarly, a significant correlation was found between Per2 and Per3 (P=0.045). Patients with lower expression of Per1, Per2 and Per3 had a shorter survival time than those with higher expression. These results indicate that loss of Per may promote tumor progression in NSCLC, and may serve as a novel prognostic biomarker of NSCLC.

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References

Liu Y, Wang L, Lin X, Wang J, Yu J, Miao Y . The transcription factor DEC1 (BHLHE40/STRA13/SHARP-2) is negatively associated with TNM stage in non-small-cell lung cancer and inhibits the proliferation through cyclin D1 in A549 and BE1 cells. Tumour Biol. 2013; 34(3):1641-50. DOI: 10.1007/s13277-013-0697-z. View

Hara Y, Onishi Y, Oishi K, Miyazaki K, Fukamizu A, Ishida N . Molecular characterization of Mybbp1a as a co-repressor on the Period2 promoter. Nucleic Acids Res. 2009; 37(4):1115-26. PMC: 2651808. DOI: 10.1093/nar/gkn1013. View

Mostafaie N, Kallay E, Sauerzapf E, Bonner E, Kriwanek S, Cross H . Correlated downregulation of estrogen receptor beta and the circadian clock gene Per1 in human colorectal cancer. Mol Carcinog. 2009; 48(7):642-7. DOI: 10.1002/mc.20510. View

Wang Y, Hua L, Lu C, Chen Z . Expression of circadian clock gene human Period2 (hPer2) in human colorectal carcinoma. World J Surg Oncol. 2011; 9:166. PMC: 3254130. DOI: 10.1186/1477-7819-9-166. View

Couto P, Miranda D, Vieira R, Vilhena A, De Marco L, Bastos-Rodrigues L . Association between CLOCK, PER3 and CCRN4L with non‑small cell lung cancer in Brazilian patients. Mol Med Rep. 2014; 10(1):435-40. DOI: 10.3892/mmr.2014.2224. View

Gibbs J, Beesley S, Plumb J, Singh D, Farrow S, Ray D . Circadian timing in the lung; a specific role for bronchiolar epithelial cells. Endocrinology. 2008; 150(1):268-76. PMC: 4340583. DOI: 10.1210/en.2008-0638. View

Cao Q, Gery S, Dashti A, Yin D, Zhou Y, Gu J . A role for the clock gene per1 in prostate cancer. Cancer Res. 2009; 69(19):7619-25. PMC: 2756309. DOI: 10.1158/0008-5472.CAN-08-4199. View

Yang X, Wood P, Ansell C, Quiton D, Oh E, Du-Quiton J . The circadian clock gene Per1 suppresses cancer cell proliferation and tumor growth at specific times of day. Chronobiol Int. 2009; 26(7):1323-39. DOI: 10.3109/07420520903431301. View

Nagel R, Clijsters L, Agami R . The miRNA-192/194 cluster regulates the Period gene family and the circadian clock. FEBS J. 2009; 276(19):5447-55. DOI: 10.1111/j.1742-4658.2009.07229.x. View

10.

Guillaumond F, Dardente H, Giguere V, Cermakian N . Differential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors. J Biol Rhythms. 2005; 20(5):391-403. DOI: 10.1177/0748730405277232. View

11.

Fu L, Lee C . The circadian clock: pacemaker and tumour suppressor. Nat Rev Cancer. 2003; 3(5):350-61. DOI: 10.1038/nrc1072. View

12.

Zhao B, Lu J, Yin J, Liu H, Guo X, Yang Y . A functional polymorphism in PER3 gene is associated with prognosis in hepatocellular carcinoma. Liver Int. 2012; 32(9):1451-9. DOI: 10.1111/j.1478-3231.2012.02849.x. View

13.

Gery S, Komatsu N, Kawamata N, Miller C, Desmond J, Virk R . Epigenetic silencing of the candidate tumor suppressor gene Per1 in non-small cell lung cancer. Clin Cancer Res. 2007; 13(5):1399-404. DOI: 10.1158/1078-0432.CCR-06-1730. View

14.

Chen S, Choo K, Hou M, Yeh K, Kuo S, Chang J . Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers. Carcinogenesis. 2005; 26(7):1241-6. DOI: 10.1093/carcin/bgi075. View

15.

Huang B, Carloss H, Wyatt S, Riley E . Hormone replacement therapy and survival in lung cancer in postmenopausal women in a rural population. Cancer. 2009; 115(18):4167-75. DOI: 10.1002/cncr.24475. View

16.

Clark S, Melki J . DNA methylation and gene silencing in cancer: which is the guilty party?. Oncogene. 2002; 21(35):5380-7. DOI: 10.1038/sj.onc.1205598. View

17.

Chen R, Yang K, Zhao N, Zhao D, Chen D, Zhao C . Abnormal expression of PER1 circadian-clock gene in oral squamous cell carcinoma. Onco Targets Ther. 2012; 5:403-7. PMC: 3513907. DOI: 10.2147/OTT.S38508. View

18.

Yeh K, Yang M, Liu T, Chen J, Chan W, Lin S . Abnormal expression of period 1 (PER1) in endometrial carcinoma. J Pathol. 2005; 206(1):111-20. DOI: 10.1002/path.1756. View

19.

Gery S, Komatsu N, Baldjyan L, Yu A, Koo D, Koeffler H . The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells. Mol Cell. 2006; 22(3):375-82. DOI: 10.1016/j.molcel.2006.03.038. View

20.

Winter S, Bosnoyan-Collins L, Pinnaduwage D, Andrulis I . Expression of the circadian clock genes Per1 and Per2 in sporadic and familial breast tumors. Neoplasia. 2007; 9(10):797-800. PMC: 2040206. DOI: 10.1593/neo.07595. View