Expression of Telomere Repeat Binding Factor 1 and TRF2 in

Research ArticleExpression of Telomere Repeat Binding Factor 1 and TRF2 inProstate Cancer and Correlation with Clinical Parameters

Wei Chen1 YongWang2 Fei Li3 Wei Lin1 Yong Liang1 and Zhiwei Ma4

1Department of Urology Zigong Fourth Peoplersquos Hospital Sichuan China2Department of Pathology Zigong Fourth Peoplersquos Hospital Sichuan China3Department of Urology Nanfang Hospital Southern Medical University Guangzhou China4Department of Urology Sichuan Academy of Medical Sciences and Sichuan Provincial Peoplersquos Hospital Chengdu China

Correspondence should be addressed to Zhiwei Ma csssmu163com

Received 17 December 2016 Accepted 15 June 2017 Published 20 July 2017

Academic Editor Paul W Doetsch

Copyright copy 2017 Wei Chen et alThis is an open access article distributed under theCreativeCommonsAttribution License whichpermits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Objective The objective of this study was to investigate the expression of telomere repeat binding factor 1 (TRF1) and TRF2in prostate cancer and their relationships with clinicopathological features Methods In total 50 prostate cancer tissues andpaired benign prostate hyperplasia tissues were analyzed The telomere-binding proteins TRF1 and TRF2 were measured usingimmunohistochemical method Correlation analyses were used to evaluate the association between immunohistochemical scoreand clinical parameters Results The expression of TRF1 was significantly higher in prostate cancer tissue than in benign prostatehyperplasia tissue (1205942 = 6269 119875 lt 001) Elevated levels of TRF2 were observed in both prostate cancer and benign prostatehyperplasia tissue (1205942 = 113 119875 = 076) TRF1 expression was significantly positively correlated with surgical capsular invasion(Spearmanrsquos 119903 = 043 119875 = 0002) seminal vesicle invasion (Spearmanrsquos 119903 = 035 119875 = 001) lymph nodes metastases (Spearmanrsquos119903 = 041 119875 = 0003) total prostate specific antigen (119903 = 061 119875 lt 005) and Gleason score (119903 = 047 119875 = 001) However therewere no significant statistical differences between prostate volume (119903 = 006 119875 = 075) and age (119903 = 014 119875 = 009) ConclusionBoth TRF1 and TRF2 were overexpressed in prostate cancer There was no specificity of TRF2 in prostate cancer while TRF1 maybe associated with prostate cancer progression

1 Introduction

Prostate cancer is the second common cancer of men indeveloped countries It is also the third cause of cancer deathin men which is secondly to lung and bronchial carcinoma[1] The prevalence of prostate cancer is gradually risingeven though the diagnostic methods were rapidly improvingTherefore it is necessary to further study the pathogenesisand diagnosismethods Telomere is an important structure ofchromosomes which plays an important role in maintainingthe stability of the chromosome [2] There were differentdegrees of telomere loss or telomere unstable phenomenon inmost tumors Studies show there was different expression incervical cancer and stomach cancer of telomere repeat bind-ing factors 1 and 2 (TRF1 and TRF2) which maintained thestability of telomere However up to now there was no studyreport about TRF1 and TRF2 expression in prostate cancer as

well as the relationship between the telomere repeat bindingfactor and clinical pathological variables [3 4] This studyintended to detect the expression of TRF1 and TRF2 inprostate cancer tissue and discuss the correlation betweenclinical pathological indicators so as to further clarify themolecular mechanisms of prostate cancer

2 Materials and Methods

21 Inclusion and ExclusionCriteria Thepresented studywasapproved by the hospital ethics committee of ZigongNumber4 Peoplersquos Hospital and all patients gave informed consentbefore operation Prostate cancer tissue and paired benignprostate hyperplasia tissue were obtained from patients whounderwent surgical resection or transrectal prostatic biopsyin Department of Urology from January 2015 to April 2016The sample size in each group was 50 cases The inclusion

HindawiBioMed Research InternationalVolume 2017 Article ID 9764752 5 pageshttpsdoiorg10115520179764752

2 BioMed Research International

criteria were (1) patients with pathological diagnosis ofprostate cancer or benign prostate hyperplasia and (2) noage restriction The exclusion criteria were as follows (1)patients with urinary tract infection or systemic infection(2) metastatic prostate cancer (3) pathological diagnosisconfirming prostatic hyperplasia accompanied by suspiciousprostate cancer cell The ages of patients in this studywere ranging from 51 to 76 years (median 62 years) Anypreoperative treatment was not applied on each patientAll patients with prostate cancer were scored according toGleason system

22 Immunohistochemical Assay All tissue specimens wereconfirmed by pathological examination Specimens wereimmediately stored at minus90 centigrade after excision Beforeantigen-antibody reaction the tissue was fixed with 4paraformaldehyde for 15min and then the 5120583m slices weremade on the paraffin slicing machine All antigen-antibodyreactions are performed in accordance with manufacturerrsquosinstructions TRF1 and TRF2 primarymonoclonal antibodieswere obtained from Abcam Co Ltd (Cambridge UK) Thedilution multiple was set as 1 100

23 Immunohistochemical Results Definition Semiquantita-tive calculation was obtained to assess the immunohisto-chemical results Brown granules were observed in positivereaction of TRF1 and TRF2 protein Five independent regionswere observed and scored at 400x magnification undermicroscope by two pathologists in each slice The final scoreof each slice was calculated from the average value of 5regions Positive cells number in slice was scored using thethree-point scale no staining observed in slice is scored 0While observed mild staining is scored as 1 observed mod-erate staining is scored as 2 and observed deep staining isscored as 3 positive cells rates were still scored using three-point scale the proportion of positive cells was scored as 0(absence of positive cells) 1 (lt10 positive cells) 2 (11-50positive cells) and 3 (gt50 positive cells)

The final immunohistochemistry score was defined aspositive cells number multiplied by positive cells rate Nega-tive was defined as 0ndash3 points 3-4 pointsmeant weak positive(+) 5ndash7 points meant moderate positive (+) and 8-9 pointsmeant strong positive (+++)

24 Statistical Analysis All statistical analyses were per-formed using SPSS version 200 (SPSS Inc Chicago IL USA)to evaluate the significance of mentioned variables Measure-ment data was expressed as mean and standard deviationChi-square test was obtained to evaluate categorical dataTwo independent Studentrsquos 119905-tests were used to determinethe different between groups One-way analysis of variancewas appropriate for data comparison between multigroupsSpearman correlation analysis was appropriate for evaluatingthe correlation between TRF1 and surgical capsule seminalvesicle invasion and lymphaticmetastasis119875 value lt 005 wasconsidered to be statistically significant

3 Results

31 Basic Characteristic between Groups A total of 50prostate cancer cases and 50 benign prostate hyperplasiacases were included in this study The mean age was 6324 plusmn1392 years (range 55sim75) in prostate cancer group and6181 plusmn 1024 years (range 57sim79) in benign prostate hyper-plasia group respectively The body mass index (BMI) was2382 plusmn 527 kgm2 in prostate cancer group and 2254 plusmn498 kgm2 in benign prostate hyperplasia group respectivelyThe total prostate specific antigen (TPSA) was 2631 plusmn819 ngml (range 176sim3612 ngml) and 175 plusmn 024 ngml(000sim319 ngml) in benign prostate hyperplasia group TheGleason score was 619 plusmn 061 (range 4sim8) in prostate cancergroup In these cases the Gleason score was higher than 7 for32 patients There were 36 cases with surgical capsular inva-sion 34 cases with seminal vesicle invasion and 25 patientswith regional lymph node metastasis according by patho-logical diagnosis Statistical differences were not detected interms of age and BMI between groups (119875 lt 005) see Table 1

32 Expression of TRF1 and TRF2 in Prostate Cancer and BPHTissue The expressions of TRF1 and TRF2 in prostate cancerandBPH tissue are provided in Figure 1 andTable 2 Immuno-histochemical results demonstrated that TRF1 protein wasmainly expressed in the nucleus both in prostate cancer andin benign prostate hyperplasia tissues However the level ofTRF1 in prostate cancer was significantly higher than that ofbenign prostate hyperplasia (1205942 = 6269 119875 lt 001) TRF2protein was more highly expressed in both prostate cancerand benign prostate hyperplasia tissues Both nucleus andcytoplasm could detect TRF2 which was mainly located innucleus There was no statistical significance between groupsin terms of immunohistochemical staining score (1205942 = 113119875 = 076)

33 Correlation of TRF1 and Clinical or Pathological Vari-ables The relations between the TRF1 stain and surgicalcapsular invasion seminal vesicle invasion and lymph nodemetastasis are provided in Table 3 and TPSA levels Gleasonscore prostate volume and age are provided in Table 4 Nosignificant relationships were found between TRF1 stain andpatientrsquos age and prostate volume (119875 = 072 119875 = 036) TheTRF1 stain was stronger in patient with surgical capsular orseminal vesicle invasion (Spearmanrsquos 119903 = 043 119875 = 0002Spearmanrsquos 119903 = 035 119875 = 001 resp) Patients with highlevel of TPSA always meet a strong stain of TRF1 (119865 = 561119875 = 001) Staining for TRF1 was stronger in advance stageof Gleason score than in lower stage of Gleason score (119865 =497 119875 = 003) Moreover TRF1 was higher in tumors frompatients with lymph nodes metastasis than in those withoutlymph nodes metastasis (Spearmanrsquos 119903 = 041 119875 = 0003)

4 Discussion

Studies have shown that telomere instability is one of themaincauses of prostate cancer Molecular biology studies suggestthat themain function of telomere is tomaintain the integrity

BioMed Research International 3

(a) (b)

(c) (d)

Figure 1 Expression of TRF1 and TRF2 in prostate cancer and benign prostate hyperplasia (times400 (a) TRF1 in prostate cancer (b) TRF1 inbenign prostate hyperplasia (c) TRF2 in prostate cancer (d) TRF2 in benign prostate hyperplasia)

Table 1 Basic characteristics between groups

Indicator PCa (119899 = 50) BPH (119899 = 50) 1199051205942 119875

Age (years old) 6324 plusmn 1392 6181 plusmn 1024 059 056BMI (kgm2) 2382 plusmn 527 2254 plusmn 498 125 021TPSA 2631 plusmn 819 175 plusmn 024 2154 lt0001Gleason score 619 plusmn 061 NA NA NASurgical capsular invasion 36 NA NA NASeminal vesicle invasion 34 NA NA NARegional lymph node metastasis 25 NA NA NAPCa prostate cancer BPH benign prostatic hyperplasia BMI body mass index PSA prostate specific antigen NA not available

of chromosomes Telomere can prevent the destruction ofchromosome structure caused by endogenous or exogenousfactors Telomere locates at the end of linear chromosomesand is composed of telomere-binding proteins and repeatTTAGGG sequence It plays an important role in tumordevelopment belonging to its cap-like structure nature [5]

51015840 RNA primer guide model is essential for semicon-servative DNA replication in cell division which also existsin chromosome replication progress However literaturereported that chromosome 31015840 end the template of DNA repli-cation usually cannot be completely copied so that telomeresat the region cannot be corresponding fully replicated [6]Generally speaking the ends of chromosomes in normal cellscannot have endless growth Cell division will be stopped andenter the stage of programmed cell death when the growth

ended [7] While chromosome semiconservative replicationprocess is not shortened the telomeres and programmedcell death will be suppressed in most malignancies Therebyconsecutive proliferation of tumor cells can be detected Oneof the reasons is that there is more highly active telomerase inthese cells which can promote the cell growth and telomereextending [8] Sarek et al demonstrated that tumor cellproliferation is regulated by different mechanisms other thantelomerase regulation [9] Research found that telomere-binding protein plays an important role in maintainingtelomere stability and telomere length regulation [9ndash11]

Studies showed that the expression and biological func-tion of telomere-binding protein are limited to telomereswhich mainly includes telomere repeat binding factor 1(TRF1) and TRF2 The structure and function of TRF1 and


Table 2 Expression of TRF1 and TRF2 in prostate cancer and benign prostatic hyperplasia

Protein Pathologylowast minus + ++ +++ Positive ratio 1205942 119875

TRF1 PCa (119899 = 50) 6 8 31 5 880 6269 lt001BPH (119899 = 50) 44 5 1 0 120

TRF2 PCa (119899 = 50) 8 7 17 18 840 113 076BPH (119899 = 50) 11 9 14 16 780

lowastPCa prostate cancer BPH benign prostatic hyperplasia

Table 3 Correlation between TRF1 and surgical capsular invasion seminal vesicle invasion and lymphatic metastasis

minus (119899 = 6) + (119899 = 8) + + (119899 = 31) +++ (119899 = 5) 1205942 119875

Surgical capsular invasion Yes 2 4 25 5 946 002No 4 4 6 0

Seminal vesicle invasion Yes 1 5 24 4 897 003No 5 3 7 1

Lymphatic metastasis Yes 0 2 20 3 1081 001No 6 6 11 2

Table 4 Correlation between TRF1 and age TPSA Gleason score and prostate volume

minus (119899 = 6) + (119899 = 8) ++ (119899 = 31) +++ (119899 = 5) 119865lowast 119875

TPSA 2108 plusmn 489 2619 plusmn 561 2791 plusmn 968 2964 plusmn 1103 561 001Gleason score 532 plusmn 084 586 plusmn 103 671 plusmn 048 861 plusmn 135 497 003Prostate volume 7832 plusmn 785 7593 plusmn 546 7569 plusmn 961 8326 plusmn 573 093 036Age 6069 plusmn 1267 6137 plusmn 1253 6648 plusmn 952 6329 plusmn 1194 035 072lowast119865 variance of 119865 value

TRF2 can antagonize or cooperatewith each other in differenttissues so that component of the network maintained theends of chromosomes stable by regulating telomere lengthand telomerase activity [12 13]The role of negative regulationof telomere terminus of TRF1 is mainly dependent on telom-erase its main function is to promote the T-loop formationlocated at telomere terminus According to its role TRF1overexpression will shorten the telomere terminus lengththus contributing to tumor cells abnormal proliferation [14ndash16] TRF2 does not depend on telomerase the main role is toprevent telomere terminus fusion and maintain the geneticinformation and telomeres structure stable [17 18]

In present study we have evaluated the differentialexpressing of TRF1 and TRF2 in prostate cancer and benignprostatic hyperplasia by immunohistochemical method Wedetected an elevated level of TRF1 and TRF2 in prostatecancer tissueOverexpression of TRF2 has been found in bothprostate cancer and benign prostatic hyperplasia whereasthere was no statistical difference between groups Furtheranalysis on the relationship between TRF1 and clinical andpathological indicators of prostate cancer found there weresignificant elevated levels of TRF1 in patients with surgicalcapsular invasion seminal vesicle invasion or lymph nodemetastasis and high level of TPSA and Gleason scores whilethere was no significant correlation with prostate volumeprostate size and age

In summary there was specific elevation of TRF1 expres-sion in prostate cancer that could be a potential indicator to

evaluate prognosis The fact that the molecular mechanismsof TRF1 impact on the biological behavior of prostate cancerneeds further research

Ethical Approval

All procedures performed in studies involving human par-ticipants were in accordance with the ethical standards ofthe institutional and national research committee and withthe 1964 Helsinki declaration and its later amendments orcomparable ethical standards

Consent

Informed consent was obtained from all individual partici-pants included in the study

Conflicts of Interest

The authors declare that they have no financial and personalrelationships with other people or organizations that caninappropriately influence their work and there is no profes-sional or other personal interest of any nature or kind in anyproduct service andor company that could be construed asinfluencing the position presented in or the review of thismanuscript


Acknowledgments

This study was funded by (1) Key Project of Zigong Scienceand Technology (2016SF07) and (2) Sichuan Medical Scien-tific Research Subject (S16087)

References

[1] S Loeb H Lilja and A Vickers ldquoBeyond prostate-specificantigen Utilizing novel strategies to screen men for prostatecancerrdquo Current Opinion in Urology vol 26 no 5 pp 459ndash4652016

[2] L Hou B T Joyce T Gao et al ldquoBlood telomere length attritionand cancer development in the normative aging study cohortrdquoEBioMedicine vol 2 no 6 pp 591ndash596 2015

[3] K Lee and L S Gollahon ldquoZSCAN4 and TRF1 A functionallyindirect interaction in cancer cells independent of telomeraseactivityrdquo Biochemical and Biophysical Research Communica-tions vol 466 no 4 pp 644ndash649 2015

[4] J Gao J Zhang Y Long and X Lu ldquoExpression of telom-ere binding proteins in gastric cancer and correlation withclinicopathological parametersrdquo Asia-Pacific Journal of ClinicalOncology vol 7 no 4 pp 339ndash345 2011

[5] Y Xu and A Goldkorn ldquoTelomere and telomerase therapeuticsin cancerrdquo Genes vol 7 no 6 article no 22 2016

[6] F Ishikawa ldquoPortrait of replication stress viewed from telom-eresrdquo Cancer Science vol 104 no 7 pp 790ndash794 2013

[7] A Trusina ldquoStress induced telomere shortening longer life withless mutationsrdquo BMC Systems Biology vol 8 article 27 2014

[8] E P Calvo and M Wasserman ldquoG-Quadruplex ligands Potentinhibitors of telomerase activity and cell proliferation in Plas-modium falciparumrdquo Molecular and Biochemical Parasitologyvol 207 no 1 pp 33ndash38 2016

[9] G Sarek P Marzec P Margalef and S J Boulton ldquoMolecularbasis of telomere dysfunction in human genetic diseasesrdquoNature Structural andMolecular Biology vol 22 no 11 pp 867ndash874 2015

[10] J Meena K Lenhard Rudolph and C Gunes ldquoTelomere Dys-function chromosomal instability and cancerrdquoRecent Results inCancer Research vol 200 pp 61ndash79 2015

[11] X Liu Y Zhou Y Lou and H Zhong ldquoKnockdown ofHNRNPA1 inhibits lung adenocarcinoma cell proliferationthrough cell cycle arrest at G0G1 phaserdquo Gene vol 576 no 2pp 791ndash797 2016

[12] D Pal U Sharma S K Singh N Kakkar and R Prasad ldquoOver-expression of telomere binding factors (TRF1 amp TRF2) in renalcell carcinoma and their inhibition by using SiRNA induceapoptosis reduce cell proliferation andmigration invitrordquo PLoSONE vol 10 no 3 article e0115651 2015

[13] K J Lebo R O Niederer and D C Zappulla ldquoA second essen-tial function of the Est1-binding arm of yeast telomerase RNArdquoRNA vol 21 no 5 pp 862ndash876 2015

[14] I Ourliac-Garnier A Poulet R Charif et al ldquoPlatination oftelomeric DNA by cisplatin disrupts recognition by TRF2 andTRF1rdquo Journal of Biological Inorganic Chemistry vol 15 no 5pp 641ndash654 2010

[15] T Nishikawa H Okamura A Nagadoi P Konig D Rhodesand Y Nishimura ldquoSolution structure of a telomeric DNAcomplex of human TRF1rdquo Structure vol 9 no 12 pp 1237ndash12512001

[16] B D Bower and J D Griffith ldquoTRF1 and TRF2 differentiallymodulate Rad51-mediated telomeric and nontelomeric dis-placement loop formation in vitrordquo Biochemistry vol 53 no 34pp 5485ndash5495 2014

[17] G Sarek J-B Vannier S Panier H J Petrini and S J BoultonldquoTRF2 recruits RTEL1 to telomeres in s phase to promote t-loopunwindingrdquoMolecular Cell vol 57 no 4 pp 622ndash635 2015

[18] Y Doksani J Y Wu T De Lange and X Zhuang ldquoSuper-resolution fluorescence imaging of telomeres reveals TRF2-dependent T-loop formationrdquoCell vol 155 no 2 pp X345ndash3562013

Submit your manuscripts athttpswwwhindawicom

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Oxidative Medicine and Cellular Longevity


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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

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Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


criteria were (1) patients with pathological diagnosis ofprostate cancer or benign prostate hyperplasia and (2) noage restriction The exclusion criteria were as follows (1)patients with urinary tract infection or systemic infection(2) metastatic prostate cancer (3) pathological diagnosisconfirming prostatic hyperplasia accompanied by suspiciousprostate cancer cell The ages of patients in this studywere ranging from 51 to 76 years (median 62 years) Anypreoperative treatment was not applied on each patientAll patients with prostate cancer were scored according toGleason system

22 Immunohistochemical Assay All tissue specimens wereconfirmed by pathological examination Specimens wereimmediately stored at minus90 centigrade after excision Beforeantigen-antibody reaction the tissue was fixed with 4paraformaldehyde for 15min and then the 5120583m slices weremade on the paraffin slicing machine All antigen-antibodyreactions are performed in accordance with manufacturerrsquosinstructions TRF1 and TRF2 primarymonoclonal antibodieswere obtained from Abcam Co Ltd (Cambridge UK) Thedilution multiple was set as 1 100

23 Immunohistochemical Results Definition Semiquantita-tive calculation was obtained to assess the immunohisto-chemical results Brown granules were observed in positivereaction of TRF1 and TRF2 protein Five independent regionswere observed and scored at 400x magnification undermicroscope by two pathologists in each slice The final scoreof each slice was calculated from the average value of 5regions Positive cells number in slice was scored using thethree-point scale no staining observed in slice is scored 0While observed mild staining is scored as 1 observed mod-erate staining is scored as 2 and observed deep staining isscored as 3 positive cells rates were still scored using three-point scale the proportion of positive cells was scored as 0(absence of positive cells) 1 (lt10 positive cells) 2 (11-50positive cells) and 3 (gt50 positive cells)

The final immunohistochemistry score was defined aspositive cells number multiplied by positive cells rate Nega-tive was defined as 0ndash3 points 3-4 pointsmeant weak positive(+) 5ndash7 points meant moderate positive (+) and 8-9 pointsmeant strong positive (+++)

24 Statistical Analysis All statistical analyses were per-formed using SPSS version 200 (SPSS Inc Chicago IL USA)to evaluate the significance of mentioned variables Measure-ment data was expressed as mean and standard deviationChi-square test was obtained to evaluate categorical dataTwo independent Studentrsquos 119905-tests were used to determinethe different between groups One-way analysis of variancewas appropriate for data comparison between multigroupsSpearman correlation analysis was appropriate for evaluatingthe correlation between TRF1 and surgical capsule seminalvesicle invasion and lymphaticmetastasis119875 value lt 005 wasconsidered to be statistically significant

3 Results

31 Basic Characteristic between Groups A total of 50prostate cancer cases and 50 benign prostate hyperplasiacases were included in this study The mean age was 6324 plusmn1392 years (range 55sim75) in prostate cancer group and6181 plusmn 1024 years (range 57sim79) in benign prostate hyper-plasia group respectively The body mass index (BMI) was2382 plusmn 527 kgm2 in prostate cancer group and 2254 plusmn498 kgm2 in benign prostate hyperplasia group respectivelyThe total prostate specific antigen (TPSA) was 2631 plusmn819 ngml (range 176sim3612 ngml) and 175 plusmn 024 ngml(000sim319 ngml) in benign prostate hyperplasia group TheGleason score was 619 plusmn 061 (range 4sim8) in prostate cancergroup In these cases the Gleason score was higher than 7 for32 patients There were 36 cases with surgical capsular inva-sion 34 cases with seminal vesicle invasion and 25 patientswith regional lymph node metastasis according by patho-logical diagnosis Statistical differences were not detected interms of age and BMI between groups (119875 lt 005) see Table 1

32 Expression of TRF1 and TRF2 in Prostate Cancer and BPHTissue The expressions of TRF1 and TRF2 in prostate cancerandBPH tissue are provided in Figure 1 andTable 2 Immuno-histochemical results demonstrated that TRF1 protein wasmainly expressed in the nucleus both in prostate cancer andin benign prostate hyperplasia tissues However the level ofTRF1 in prostate cancer was significantly higher than that ofbenign prostate hyperplasia (1205942 = 6269 119875 lt 001) TRF2protein was more highly expressed in both prostate cancerand benign prostate hyperplasia tissues Both nucleus andcytoplasm could detect TRF2 which was mainly located innucleus There was no statistical significance between groupsin terms of immunohistochemical staining score (1205942 = 113119875 = 076)

33 Correlation of TRF1 and Clinical or Pathological Vari-ables The relations between the TRF1 stain and surgicalcapsular invasion seminal vesicle invasion and lymph nodemetastasis are provided in Table 3 and TPSA levels Gleasonscore prostate volume and age are provided in Table 4 Nosignificant relationships were found between TRF1 stain andpatientrsquos age and prostate volume (119875 = 072 119875 = 036) TheTRF1 stain was stronger in patient with surgical capsular orseminal vesicle invasion (Spearmanrsquos 119903 = 043 119875 = 0002Spearmanrsquos 119903 = 035 119875 = 001 resp) Patients with highlevel of TPSA always meet a strong stain of TRF1 (119865 = 561119875 = 001) Staining for TRF1 was stronger in advance stageof Gleason score than in lower stage of Gleason score (119865 =497 119875 = 003) Moreover TRF1 was higher in tumors frompatients with lymph nodes metastasis than in those withoutlymph nodes metastasis (Spearmanrsquos 119903 = 041 119875 = 0003)

4 Discussion

Studies have shown that telomere instability is one of themaincauses of prostate cancer Molecular biology studies suggestthat themain function of telomere is tomaintain the integrity


(a) (b)

(c) (d)












TRF1 PCa (119899 = 50) 6 8 31 5 880 6269 lt001BPH (119899 = 50) 44 5 1 0 120

TRF2 PCa (119899 = 50) 8 7 17 18 840 113 076BPH (119899 = 50) 11 9 14 16 780



minus (119899 = 6) + (119899 = 8) + + (119899 = 31) +++ (119899 = 5) 1205942 119875





minus (119899 = 6) + (119899 = 8) ++ (119899 = 31) +++ (119899 = 5) 119865lowast 119875






Ethical Approval


Consent





Acknowledgments


References
























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















(a) (b)

(c) (d)












TRF1 PCa (119899 = 50) 6 8 31 5 880 6269 lt001BPH (119899 = 50) 44 5 1 0 120

TRF2 PCa (119899 = 50) 8 7 17 18 840 113 076BPH (119899 = 50) 11 9 14 16 780



minus (119899 = 6) + (119899 = 8) + + (119899 = 31) +++ (119899 = 5) 1205942 119875





minus (119899 = 6) + (119899 = 8) ++ (119899 = 31) +++ (119899 = 5) 119865lowast 119875






Ethical Approval


Consent





Acknowledgments


References
























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















TRF1 PCa (119899 = 50) 6 8 31 5 880 6269 lt001BPH (119899 = 50) 44 5 1 0 120

TRF2 PCa (119899 = 50) 8 7 17 18 840 113 076BPH (119899 = 50) 11 9 14 16 780



minus (119899 = 6) + (119899 = 8) + + (119899 = 31) +++ (119899 = 5) 1205942 119875





minus (119899 = 6) + (119899 = 8) ++ (119899 = 31) +++ (119899 = 5) 119865lowast 119875






Ethical Approval


Consent





Acknowledgments


References
























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Acknowledgments


References
























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Documents

Expression of Telomere Repeat Binding Factor 1 and TRF2 in