PER3 VNTR GENOTYPES MAY PREDICT OVERALL SURVIVAL IN BLADDER CANCER PATIENTS IN THE TURKISH POPULATION

Yıl 2020, Cilt: 6 Sayı: 1, 120 - 135, 30.06.2020

Zeynep Yeğin , Filiz Özen , Yasin Altinisik , İbrahim Yıldırım , Asıf Yıldırım

https://doi.org/10.22531/muglajsci.695085

Cited By: 1

Öz

Circadian genes were proven to play significant roles in tumor development and progression via coordinating various cellular processes. Though circadian rhythm disturbances both on the level of expression and genetic variant analysis have been associated with increased risk for many cancer types, none has investigated the potential effect of PER3 VNTR in bladder tumorigenesis yet. In this study, we aimed to assess PER3 VNTR’s effect in terms of creating susceptibility to bladder carcinoma formation. Our second target was to enlighten the possible associations between PER3 genotypes and clinicopathological correlations in bladder carcinoma cohort and thus evaluate outcomes in bladder carcinoma prognosis. In this case-control study, 116 patients and 120 healthy controls were recruited. DNA was isolated from peripheral blood using the standard salting-out procedure and PER3 VNTR variants (ins/del polymorphism) were determined with PCR technique to distinguish the 5-repeats allele (401 bp) from the 4-repeats allele (347 bp). Though this exploratory analysis did not provide evidence supporting the role of PER3 VNTR in the onset of bladder carcinoma, it enabled us to make a risk assessment for the prognosis of bladder carcinoma patients. The survival times of patients decreased in the patient group (progression and cystectomy positive) for PER3 4/4 genotype and (recurrence, progression and cystectomy positive) for PER3 4/5 genotype. Results presented in this study are highly recommended to be investigated and validated in larger samples in different populations and ethnicities to generalize potential clinical utility.

Anahtar Kelimeler

Bladder carcinoma, circadian genes, PER3, VNTR, survival

Kaynakça

• [1] Chen, ST., Choo, KB., Hou, MF., Yeh, KT., Kuo, SJ., Chang, JG., “Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers”, Carcinogenesis, 26(7),1241-6, 2005.
• [2] Lin, YM., Chang, JH., Yeh, KT., Yang, MY., Liu, TC., Lin, SF., Su, WW., Chang, JG., “Disturbance of circadian gene expression in hepatocellular carcinoma”, Mol Carcinog, 47(12),925-33, 2008.
• [3] Mazzoccoli, G., Panza, A., Valvano, MR., Palumbo, O., Carella, M., Pazienza, V., Biscaglia, G., Tavano, F., Di Sebastiano, P., Andriulli, A., Piepoli, A., “Clock gene expression levels and relationship with clinical and pathological features in colorectal cancer patients”, Chronobiol Int, 28(10),841-51, 2011.
• [4] Huisman, SA., Ahmadi, AR., IJzermans, JN., Verhoef, C., van der Horst, GT., de Bruin, RW., “Disruption of clock gene expression in human colorectal liver metastases”, Tumour Biol, 37(10),13973-13981, 2016.
• [5] Liu, B., Xu, K., Jiang, Y., Li, X., “Aberrant expression of Per1, Per2 and Per3 and their prognostic relevance in non-small cell lung cancer”, Int J Clin Exp Pathol, 7(11),7863-71, 2014.
• [6] Li, YY., Jin, F., Zhou, JJ., Yu, F., Duan, XF., He, XY., Wang, R., Wu, WL., Long, JH., Luo, XL., “Downregulation of the circadian Period family genes is positively correlated with poor head and neck squamous cell carcinoma prognosis”, Chronobiol Int, 36(12),1723-1732, 2019.
• [7] Bass, J., Takahashi, JS., “Circadian integration of metabolism and energetics”, Science, 330(6009),1349-54, 2010.
• [8] Dijk, DJ., Archer, SN., “PERIOD3, circadian phenotypes, and sleep homeostasis”, Sleep Med Rev, 14(3),151-60, 2010.
• [9] Benedetti, F., Dallaspezia, S., Colombo, C., Pirovano, A., Marino, E., Smeraldi, E., “A length polymorphism in the circadian clock gene Per3 influences age at onset of bipolar disorder”, Neurosci Lett, 445(2),184-7, 2008.
• [10] Guess, J., Burch, JB., Ogoussan, K., Armstead, CA., Zhang, H., Wagner, S., Hebert, JR., Wood, P., Youngstedt, SD., Hofseth, LJ., Singh, UP., Xie, D., Hrushesky, WJ., “Circadian disruption, Per3, and human cytokine secretion”, Integr Cancer Ther, 8(4),329-36, 2009.
• [11] Miller, SA., Dykes, DD., Polesky, HF., “A simple salting out procedure for extracting DNA from human nucleated cells”, Nucleic Acids Res, 16(3),1215, 1988.
• [12] Fu, L., Pelicano, H., Liu, J., Huang, P., Lee, C., “The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo”, Cell, 111(1),41-50, 2002.
• [13] Yang, MY., Chang, JG., Lin, PM., Tang, KP., Chen, YH., Lin, HY., Liu, TC., Hsiao, HH., Liu, YC., Lin, SF., “Downregulation of circadian clock genes in chronic myeloid leukemia: alternative methylation pattern of hPER3”, Cancer Sci, 97(12),1298-307, 2006.
• [14] Oshima, T., Takenoshita, S., Akaike, M., Kunisaki, C., Fujii, S., Nozaki, A., Numata, K., Shiozawa, M., Rino, Y., Tanaka, K., Masuda, M., Imada, T., “Expression of circadian genes correlates with liver metastasis and outcomes in colorectal cancer”, Oncol Rep, 25(5),1439-46, 2011.
• [15] Wang, X., Yan, D., Teng, M., Fan, J., Zhou, C., Li, D., Qiu, G., Sun, X., Li, T., Xing, T., Tang, H., Peng, X., Peng, Z., “Reduced expression of PER3 is associated with incidence and development of colon cancer”, Ann Surg Oncol, 19(9),3081-8, 2012.
• [16] Relles, D., Sendecki, J., Chipitsyna, G., Hyslop, T., Yeo, CJ., Arafat, HA., “Circadian gene expression and clinicopathologic correlates in pancreatic cancer”, J Gastrointest Surg, 17(3),443-50, 2013.
• [17] Yang, MY., Lin, PM., Hsiao, HH., Hsu, JF., Lin, HY., Hsu, CM., Chen, IY., Su, SW., Liu, YC., Lin, SF., “Up-regulation of PER3 Expression Is Correlated with Better Clinical Outcome in Acute Leukemia”, Anticancer Res, 35(12),6615-22, 2015.
• [18] Lesicka, M., Jabłońska, E., Wieczorek, E., Seroczyńska, B., Siekierzycka, A., Skokowski, J., Kalinowski, L., Wąsowicz, W., Reszka, E., “Altered circadian genes expression in breast cancer tissue according to the clinical characteristics”, PLoS One, 13(6),e0199622, 2018.
• [19] Zhu, Y., Brown, HN., Zhang, Y., Stevens, RG., Zheng, T., “Period3 structural variation: a circadian biomarker associated with breast cancer in young women”, Cancer Epidemiol Biomarkers Prev, 14(1),268-70, 2005.
• [20] Chu, LW., Zhu, Y., Yu, K., Zheng, T., Yu, H., Zhang, Y., Sesterhenn, I., Chokkalingam, AP., Danforth, KN., Shen, MC., Stanczyk, FZ., Gao, YT., Hsing, AW., “Variants in circadian genes and prostate cancer risk: a population-based study in China”, Prostate Cancer Prostatic Dis, 11(4),342-8, 2008.
• [21] Zhao, B., Lu, J., Yin, J., Liu, H., Guo, X., Yang, Y., Ge, N., Zhu, Y., Zhang, H., Xing, J., “A functional polymorphism in PER3 gene is associated with prognosis in hepatocellular carcinoma”, Liver Int, 32(9),1451-9, 2012.
• [22] Karantanos, T., Theodoropoulos, G., Gazouli, M., Vaiopoulou, A., Karantanou, C., Stravopodis, DJ., Bramis, K., Lymperi, M., Pektasidis, D., “Association of the clock genes polymorphisms with colorectal cancer susceptibility”, J Surg Oncol, 108(8),563-7, 2013.
• [23] Zhang, Z., Ma, F., Zhou, F., Chen, Y., Wang, X., Zhang, H., Zhu, Y., Bi, J., Zhang, Y., “Functional polymorphisms of circadian negative feedback regulation genes are associated with clinical outcome in hepatocellular carcinoma patients receiving radical resection”, Med Oncol, 31(12),179, 2014.
• [24] 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, 10(1),435-40, 2014.
• [25] Madden, MH., Anic, GM., Thompson, RC., Nabors, LB., Olson, JJ., Browning, JE., Monteiro, AN., Egan, KM., “Circadian pathway genes in relation to glioma risk and outcome”, Cancer Causes Control, 25(1),25-32, 2014.
• [26] Qu, F., Qiao, Q., Wang, N., Ji, G., Zhao, H., He, L., Wang, H., Bao, G., “Genetic polymorphisms in circadian negative feedback regulation genes predict overall survival and response to chemotherapy in gastric cancer patients”, Sci Rep, 6,22424, 2016.
• [27] Gutiérrez-Monreal, MA., Villela, L., Baltazar, S., Perfecto-Avalos, Y., Cardineau, GA., Scott, SP., “A PER3 polymorphism is associated with better overall survival in diffuse large B-cell lymphoma in Mexican population”, Cancer Biomark, 15(5),699-705, 2015.
• [28] Alexander, M., Burch, JB., Steck, SE., Chen, CF., Hurley, TG., Cavicchia, P., Ray, M., Shivappa, N., Guess, J., Zhang, H,, Youngstedt, SD., Creek, KE., Lloyd, S., Yang, X., Hébert, JR., “Case-control study of the PERIOD3 clock gene length polymorphism and colorectal adenoma formation”, Oncol Rep, 33(2),935-41, 2015.
• [29] Johnson, K., Chang-Claude, J., Critchley, AM., Kyriacou, C., Lavers, S., Rattay, T., Seibold, P., Webb, A., West, C., Symonds, RP., Talbot, CJ., “Genetic Variants Predict Optimal Timing of Radiotherapy to Reduce Side-effects in Breast Cancer Patients”, Clin Oncol (R Coll Radiol), 31(1),9-16, 2019.