Top

Journal of Orthopaedic Surgery and Research

Published in:

Open Access 01-12-2016 | Research article

Verification of TREX1 as a promising indicator of judging the prognosis of osteosarcoma

Authors: Jinyi Feng, Ruilong Lan, Guanxiong Cai, Jinluan Lin, Xinwen Wang, Jianhua Lin, Deping Han

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2016

Abstract

Background

The study aimed to explore the correlation between the expression of TREX1 and the metastasis and the survival time of patients with osteosarcoma as well as biological characteristics of osteosarcoma cells for the prognosis judgment of osteosarcoma.

Method

The correlation between the expression of TREX1 protein and the occurrence of pulmonary metastasis in 45 cases of osteosarcoma was analyzed. The CD133⁺ and CD133⁻ cell subsets of osteosarcoma stem cells were sorted by the flow cytometry. The tumorsphere culture, clone formation, growth curve, osteogenic and adipogenic differentiation, tumor-formation ability in nude mice, sensitivity of chemotherapeutic drugs, and other cytobiology behaviors were compared between the cell subsets in two groups; the expressions of stem cell-related genes Nanog and Oct4 were compared; The expressions of TREX1 protein and mRNA were compared between the cell subsets in two groups. The data was statistically analyzed. The measurement data between the two groups were compared using t test. The count data between the two groups were compared using χ ² test and Kaplan–Meier survival analysis. A P value <0.05 indicated that the difference was statistically significant.

Results

The expression of TREX1 protein in patients with osteosarcoma in the metastasis group was significantly lower than that in the non-metastasis group. The difference was statistically significant (P < 0.05). Up to the last follow-up visit, the former average survival time was significantly lower than that of the latter, and the difference was statistically significant (P < 0.05). The expression of TREX1 in human osteosarcoma CD133⁺ cell subsets was significantly lower than that in CD133^- cell subsets. Stemness-related genes Nanog and Oct4 were highly expressed in human osteosarcoma CD133⁺ cell subsets with lower expression of TREX1; the biological characteristics identification experiment showed that human CD133⁺ cell subsets with low TREX1 expression could form tumorspheres, the number of colony forming was more, the cell proliferation ability was strong, the osteogenic and adipogenic differentiation potential was big, the tumor-forming ability in nude mice was strong, and the sensibility of chemotherapeutics drugs on cisplatin was low.

Conclusions

The expression of TREX1 may be related to metastasis in patients with osteosarcoma. The expression of TREX1 was closely related to the cytobiology characteristics of osteosarcoma stem cell. TREX1 can play an important role in the occurrence and development processes. And, TREX1 is expected to become an effective new index for the evaluation of the prognosis.

Bielack SS, Carrle D, Hardes J, Schuck A, Paulussen M. Bone tumors in adolescents and young adults. Curr Treat Options Oncol. 2008;9:67–80.CrossRefPubMed

Bacci G, Rocca M, Salone M, Balladeli A, Ferrari S, Palmerini E, Forni C, Briccoli A. High grade osteosarcoma of the extremities with lung metastases at presentation: treatment with neoadjuvant chemotherapy and simultaneous resection of primary and metastatic lesions. J Surg Oncol. 2008;98:415–20.CrossRefPubMed

Krishnan K, Khanna C, Helman LJ. The biology of metastases in pediatric sarcomas. Cancer J. 2005;11:306–13.CrossRefPubMed

Hingorani P, Zhang WD, Gorlick R, Kolb EA. Inhibition of Src phosphorylation alters metastatic potential of osteosarcoma in vitro but not in vivo. Clin Cancer Res. 2009;15:3416–22.CrossRefPubMed

Ren L, Hong SH, Cassavaugh J, Osborne T, Chou AJ, Kim SY, Gorlick R, Hewitt SM, Khanna C. The actin-cytoskeleton linker protein ezrin is regulated during osteosarcoma metastasis by PKC. Oncogene. 2009;28:792–802.CrossRefPubMed

Yan GN, Lv YF, Guo QN. Advances in osteosarcoma stem cell research and opportunities for novel therapeutic targets. Cancer Lett. 2016;370:268–74.CrossRefPubMed

Tirino V, Desiderio V, Paino F, De Rosa A, Papaccio F, Fazioli F, Pirozzi G, Papaccio G. Human primary bone sarcomas contain CD133+ cancer stem cells displaying high tumorigenicity in vivo. FASEB J. 2011;25:2022–30.CrossRefPubMed

Brucet M, Querol-Audí J, Serra M, Ramirez-Espain X, Bertlik K, Ruiz L, Lloberas J, Macias MJ, Fita I, Celada A. Structure of the dimeric exonuclease TREX1 in complex with DNA displays a proline-rich binding site for WW Domains. J Biol Chem. 2007;282:14547–57.CrossRefPubMed

Pulliero A, Marengo B, Domenicotti C, Longobardi MG, Fazzi E, Orcesi S, Bianchi M, Balottin U, Izzotti A. Inhibition of neuroblastoma cell growth by TREX1-mutated human lymphocytes. Oncol Rep. 2012;27:1689–94.PubMed

10.

Tomicic MT, Aasland D, Nikolova T, Kaina B, Christmann M. Human three prime exonuclease TREX1 is induced by genotoxic stress and involved in protection of glioma and melanoma cells to anticancer drugs. Biochim Biophys Acta. 1833;2013:1832–43.

11.

Aringer M, Gunther C, Lee-Kirsch MA. Innate immune processes in lupus erythematosus. Clin Immunol. 2013;147:216–22.CrossRefPubMed

12.

Dong XQ, Jiao L, Li YN, Evans DB, Wang HM, Hess KR, Abbruzzese JL, Li DH. Significant associations of mismatch repair gene polymorphisms with clinical outcome of pancreatic cancer. J Clin Oncol. 2009;27:1592–9.CrossRefPubMedPubMedCentral

13.

Miyazaki T, Kim YS, Yoon J, Wang H, Suzuki T, Morse HC. The 3 ′-5 ′ DNA exonuclease TREX1 directly interacts with poly(ADP-ribose) polymerase-1 (PARP1) during the DNA damage response. J Biol Chem. 2014;289:32548–58.CrossRefPubMedPubMedCentral

14.

Grieves JL, Fye JM, Harvey S, Grayson JM, Hollis T, Perrino FW. Exonuclease TREX1 degrades double-stranded DNA to prevent spontaneous lupus-like inflammatory disease. Proc Natl Acad Sci U S A. 2015;112:5117–22.CrossRefPubMedPubMedCentral

15.

Broadhead ML, Clark JC, Myers DE, Dass CR, Choong PF. The molecular pathogenesis of osteosarcoma: a review. Sarcoma. 2011;2011:959248.CrossRefPubMedPubMedCentral

16.

Bebenek K, Matsuda T, Masutani C, Hanaoka F, Kunkel TA. Proofreading of DNA polymerase eta-dependent replication errors. J Biol Chem. 2001;276:2317–20.CrossRefPubMed

17.

Mazur DJ, Perrino FW. Structure and expression of the TREX1 and TREX2 3′ -> 5′ exonuclease genes. J Biol Chem. 2001; 276: 14718–27.

18.

Höss M, Robins P, Naven TJ, Pappin DJ, Sgouros J, Lindahl T. A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein. EMBO J. 1999;18:3868–75.CrossRefPubMedPubMedCentral

19.

Mazur DJ, Perrino FW. Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3′->5′ exonucleases. J Biol Chem. 1999; 274: 19655–60.

20.

Dong X, Li Y, Hess KR, Abbruzzese JL, Li D. DNA mismatch repair gene polymorphisms affect survival in pancreatic cancer. Oncologist. 2011;16:61–70.CrossRefPubMedPubMedCentral

21.

Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001;414:105–11.CrossRefPubMed

22.

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003;100:3983–8.CrossRefPubMedPubMedCentral

23.

Tirino V, Desiderio V, d'Aquino R, De Francesco F, Pirozzi G, Graziano A, Galderisi U, Cavaliere C, De Rosa A, Papaccio G, Giordano A. Detection and characterization of CD133⁺ cancer stem cells in human solid tumours. PLoS One. 2008;3:e3469.CrossRefPubMedPubMedCentral

24.

Adhikari AS, Agarwal N, Wood BM, Porretta C, Ruiz B, Pochampally RR, Iwakuma T. CD117 and Stro-1 identify osteosarcoma tumor-initiating cells associated with metastasis and drug resistance. Cancer Res. 2010;70:4602–12.CrossRefPubMedPubMedCentral

25.

Martins-Neves SR, Lopes ÁO, do Carmo A, Paiva AA, Simões PC, Abrunhosa AJ, Gomes CM. Therapeutic implications of an enriched cancer stem-like cell population in a human osteosarcoma cell line. BMC Cancer. 2012;12:139.CrossRefPubMedPubMedCentral

26.

Chowdhury D, Beresford PJ, Zhu P, Zhang D, Sung JS, Demple B, Perrino FW, Lieberman J. The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death. Mol Cell. 2006;23:133–42.CrossRefPubMed

Title: Verification of TREX1 as a promising indicator of judging the prognosis of osteosarcoma
Authors: Jinyi Feng
Ruilong Lan
Guanxiong Cai
Jinluan Lin
Xinwen Wang
Jianhua Lin
Deping Han
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Orthopaedic Surgery and Research / Issue 1/2016
Electronic ISSN: 1749-799X
DOI: https://doi.org/10.1186/s13018-016-0487-6

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Verification of TREX1 as a promising indicator of judging the prognosis of osteosarcoma

Abstract

Background

Method

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Method

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2016

Radiographic results after plaster cast fixation for 10 days versus 1 month in reduced distal radius fractures: a prospective randomised study

Biological and functional evaluation of a novel pyrolytic carbon implant for the treatment of focal osteochondral defects in the medial femoral condyle: assessment in a canine model

Clinical evaluation of an allogeneic bone matrix containing viable osteogenic cells in patients undergoing one- and two-level posterolateral lumbar arthrodesis with decompressive laminectomy

Surgical treatment of popliteal cyst: a systematic review and meta-analysis

Biomechanical effects of morphological variations of the cortical wall at the bone-cement interface

A non-invasive, home-based biomechanical therapy for patients with spontaneous osteonecrosis of the knee