Top

Published in:

Open Access 01-12-2021 | Metastasis | Research

Expressions of TWIST1 and CD105 markers in colorectal cancer patients and their association with metastatic potential and prognosis

Authors: Fahimeh Fattahi, Leili Saeednejad Zanjani, Somayeh Vafaei, Zohreh Habibi Shams, Jafar Kiani, Marzieh Naseri, Elmira Gheytanchi, Zahra Madjd

Published in: Diagnostic Pathology | Issue 1/2021

Abstract

Background

TWIST1 and CD105, which contribute to tumor malignancy, are overexpressed in cancers. Accordingly, TWIST1 enhances epithelial-to-mesenchymal transition (EMT) and promotes the formation of cancer stem cells (CSCs). Also, CD105 is a neoangiogenesis marker in endothelial cells, which is introduced as a CSC marker in tumoral epithelial cells in several types of cancers. The present study was aimed to investigate expressions of TWIST1 and CD105 in colorectal cancer (CRC) patients.

Methods

Expressions of TWIST1 and CD105 in 250 CRC tissue samples were evaluated using immunohistochemistry on tissue microarrays (TMAs). In this regard, TWIST1 expression was investigated in the subcellular locations (cytoplasm and nucleus), while CD105 was mapped in endothelial cells and cytoplasmic tumor cells of CRC tissues. The association between the expression of these markers and clinicopathological parameters, as well as survival outcomes were analyzed.

Results

Results indicate a statistically significant association between higher nuclear expression levels of TWIST1 and distant metastases in CRC (P = 0.040) patients. In addition, it was shown that the increased nuclear expression of TWIST1 had a poor prognostic value for disease-specific survival (DSS) and progression-free survival (PFS) (P = 0.042, P = 0.043, respectively) in patients with CRC. Moreover, analysis of CD105 expression level has revealed that there is a statistically significant association between the increased expression of CD105 in tumoral epithelial cells and more advanced TNM stage (P = 0.050).

Conclusions

Our results demonstrate that nuclear TWIST1 and cytoplasmic CD105 expressions in tumor cells had associations with more aggressive tumor behavior and more advanced diseases in CRC cases.

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. https://doi.org/10.3322/caac.21492.CrossRefPubMed

Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383(9927):1490–502. https://doi.org/10.1016/S0140-6736(13)61649-9.CrossRefPubMed

Peluso G, Incollingo P, Calogero A, Tammaro V, Rupealta N, Chiacchio G, et al. Current tissue molecular markers in colorectal Cancer: a literature review. Biomed Res Int. 2017:2605628.

Zhou P, Li B, Liu F, Zhang M, Wang Q, Liu Y, Yao Y, Li D, et al. The epithelial to mesenchymal transition (EMT) and cancer stem cells: implication for treatment resistance in pancreatic cancer. Mol Cancer. 2017;16(1):52. https://doi.org/10.1186/s12943-017-0624-9.CrossRefPubMedPubMedCentral

Guarino M. Epithelial-mesenchymal transition and tumour invasion. Int J Biochem Cell Biol. 2007;39(12):2153–60. https://doi.org/10.1016/j.biocel.2007.07.011.CrossRefPubMed

Lamouille S, Xu J, Derynck R. Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2014;15(3):178–96. https://doi.org/10.1038/nrm3758.CrossRefPubMedPubMedCentral

Ieda T, Tazawa H, Okabayashi H, Yano S, Shigeyasu K, Kuroda S, Ohara T, Noma K, Kishimoto H, Nishizaki M, Kagawa S, Shirakawa Y, Saitou T, Imamura T, Fujiwara T, et al. Visualization of epithelial-mesenchymal transition in an inflammatory microenvironment-colorectal cancer network. Sci Rep. 2019;9(1):16378. https://doi.org/10.1038/s41598-019-52816-z.CrossRefPubMedPubMedCentral

Gurzu S, Silveanu C, Fetyko A, Butiurca V, Kovacs Z, Jung I. Systematic review of the old and new concepts in the epithelial-mesenchymal transition of colorectal cancer. World J Gastroenterol. 2016;22(30):6764–75. https://doi.org/10.3748/wjg.v22.i30.6764.CrossRefPubMedPubMedCentral

Brabletz T, Kalluri R, Nieto MA, Weinberg RA. EMT in cancer. Nat Rev Cancer. 2018;18(2):128–34. https://doi.org/10.1038/nrc.2017.118.CrossRefPubMed

10.

Piccinin S, Tonin E, Sessa S, Demontis S, Rossi S, Pecciarini L, Zanatta L, Pivetta F, Grizzo A, Sonego M, Rosano C, Tos APD, Doglioni C, Maestro R, et al. A "twist box" code of p53 inactivation: twist box: p53 interaction promotes p53 degradation. Cancer Cell. 2012;22(3):404–15. https://doi.org/10.1016/j.ccr.2012.08.003.CrossRefPubMed

11.

Zhao Z, Rahman MA, Chen ZG, Shin DM. Multiple biological functions of Twist1 in various cancers. Oncotarget. 2017;8(12):20380–93. https://doi.org/10.18632/oncotarget.14608.CrossRefPubMedPubMedCentral

12.

Zhu QQ, Ma C, Wang Q, Song Y, Lv T. The role of TWIST1 in epithelial-mesenchymal transition and cancers. Tumour Biol. 2016;37(1):185–97. https://doi.org/10.1007/s13277-015-4450-7.CrossRefPubMed

13.

Singh S, Mak IWY, Handa D, Ghert M. The role of TWIST in angiogenesis and cell migration in Giant cell tumor of bone. Adv Biol. 2014:1–8.

14.

Zhu DJ, Chen XW, Zhang WJ, Wang JZ, Ouyang MZ, Zhong Q, Liu CC, et al. Twist1 is a potential prognostic marker for colorectal cancer and associated with chemoresistance. Am J Cancer Res. 2015;5(6):2000–11.PubMedPubMedCentral

15.

Chen H-F, Huang C-H, Liu C-J, Hung J-J, Hsu C-C, Teng S-C, Wu KJ, et al. Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis. Nat Commun. 2014;5(1):4697. https://doi.org/10.1038/ncomms5697.CrossRefPubMed

16.

Sun T, Zhao N, Zhao XL, Gu Q, Zhang SW, Che N, Wang XH, du J, Liu YX, Sun BC, et al. Expression and functional significance of Twist1 in hepatocellular carcinoma: its role in vasculogenic mimicry. Hepatology. 2010;51(2):545–56. https://doi.org/10.1002/hep.23311.CrossRefPubMed

17.

Hao Y, Baker D, Ten Dijke P. TGF-beta-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis. Int J Mol Sci. 2019;20:11.

18.

Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 2009;19(2):156–72. https://doi.org/10.1038/cr.2009.5.CrossRefPubMed

19.

Cheifetz S, Bellon T, Cales C, Vera S, Bernabeu C, Massague J, et al. Endoglin is a component of the transforming growth factor-beta receptor system in human endothelial cells. J Biol Chem. 1992;267(27):19027–30. https://doi.org/10.1016/S0021-9258(18)41732-2.CrossRefPubMed

20.

Hu J, Guan W, Yan L, Ye Z, Wu L, Xu H. Cancer stem cell marker Endoglin (CD105) induces epithelial Mesenchymal transition (EMT) but not metastasis in clear cell renal cell carcinoma. Stem Cells Int. 2019:9060152.

21.

Nomura Y, Yamashita T, Oishi N, Nio K, Hayashi T, Yoshida M, Hayashi T, Hashiba T, Asahina Y, Okada H, Sunagozaka H, Takatori H, Honda M, Kaneko S, et al. De novo emergence of Mesenchymal stem-like CD105(+) Cancer cells by cytotoxic agents in human hepatocellular carcinoma. Transl Oncol. 2017;10(2):184–9. https://doi.org/10.1016/j.tranon.2017.01.005.CrossRefPubMedPubMedCentral

22.

Nassiri F, Cusimano MD, Scheithauer BW, Rotondo F, Fazio A, Yousef GM, Syro LV, Kovacs K, Lloyd RV, et al. Endoglin (CD105): a review of its role in angiogenesis and tumor diagnosis, progression and therapy. Anticancer Res. 2011;31(6):2283–90.PubMed

23.

Bernabeu C, Lopez-Novoa JM, Quintanilla M. The emerging role of TGF-beta superfamily coreceptors in cancer. Biochim Biophys Acta. 2009;1792(10):954–73. https://doi.org/10.1016/j.bbadis.2009.07.003.CrossRefPubMed

24.

Minhajat R, Mori D, Yamasaki F, Sugita Y, Satoh T, Tokunaga O. Organ-specific endoglin (CD105) expression in the angiogenesis of human cancers. Pathol Int. 2006;56(12):717–23. https://doi.org/10.1111/j.1440-1827.2006.02037.x.CrossRefPubMed

25.

Saroufim A, Messai Y, Hasmim M, Rioux N, Iacovelli R, Verhoest G, Bensalah K, Patard JJ, Albiges L, Azzarone B, Escudier B, Chouaib S, et al. Tumoral CD105 is a novel independent prognostic marker for prognosis in clear-cell renal cell carcinoma. Br J Cancer. 2014;110(7):1778–84. https://doi.org/10.1038/bjc.2014.71.CrossRefPubMedPubMedCentral

26.

Nikiteas NI, Tzanakis N, Theodoropoulos G, Atsaves V, Christoni Z, Karakitsos P, Lazaris AC, Papachristodoulou A, Klonaris C, Gazouli M, et al. Vascular endothelial growth factor and endoglin (CD-105) in gastric cancer. Gastric Cancer. 2007;10(1):12–7. https://doi.org/10.1007/s10120-006-0401-8.CrossRefPubMed

27.

Nogues A, Gallardo-Vara E, Zafra MP, Mate P, Marijuan JL, Alonso A, et al. Endoglin (CD105) and VEGF as potential angiogenic and dissemination markers for colorectal cancer. World J Surg Oncol. 2020;18(1):99. https://doi.org/10.1186/s12957-020-01871-2.CrossRefPubMedPubMedCentral

28.

Romani AA, Borghetti AF, Del Rio P, Sianesi M, Soliani P. The risk of developing metastatic disease in colorectal cancer is related to CD105-positive vessel count. J Surg Oncol. 2006;93(6):446–55. https://doi.org/10.1002/jso.20456.CrossRefPubMed

29.

Weiser MR. AJCC 8th edition: colorectal Cancer. Ann Surg Oncol. 2018;25(6):1454–5. https://doi.org/10.1245/s10434-018-6462-1.CrossRefPubMed

30.

Erfani E, Roudi R, Rakhshan A, Sabet MN, Shariftabrizi A, Madjd Z. Comparative expression analysis of putative cancer stem cell markers CD44 and ALDH1A1 in various skin cancer subtypes. Int J Biol Markers. 2016;31(1):e53–61. https://doi.org/10.5301/jbm.5000165.CrossRefPubMed

31.

Camp RL, Charette LA, Rimm DL. Validation of tissue microarray technology in breast carcinoma. Lab Investig. 2000;80(12):1943–9. https://doi.org/10.1038/labinvest.3780204.CrossRefPubMed

32.

McCarty KS Jr, Szabo E, Flowers JL, Cox EB, Leight GS, Miller L, et al. Use of a monoclonal anti-estrogen receptor antibody in the immunohistochemical evaluation of human tumors. Cancer Res. 1986;46(8 Suppl):4244s–8s.PubMed

33.

Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139(5):871–90. https://doi.org/10.1016/j.cell.2009.11.007.CrossRefPubMed

34.

Georgakopoulos-Soares I, Chartoumpekis DV, Kyriazopoulou V, Zaravinos A. EMT factors and metabolic pathways in Cancer. Front Oncol. 2020;10:499. https://doi.org/10.3389/fonc.2020.00499.CrossRefPubMedPubMedCentral

35.

Wushou A, Hou J, Zhao YJ, Shao ZM. Twist-1 up-regulation in carcinoma correlates to poor survival. Int J Mol Sci. 2014;15(12):21621–30. https://doi.org/10.3390/ijms151221621.CrossRefPubMedPubMedCentral

36.

Hosono S, Kajiyama H, Terauchi M, Shibata K, Ino K, Nawa A, Kikkawa F, et al. Expression of twist increases the risk for recurrence and for poor survival in epithelial ovarian carcinoma patients. Br J Cancer. 2007;96(2):314–20. https://doi.org/10.1038/sj.bjc.6603533.CrossRefPubMedPubMedCentral

37.

Fondrevelle ME, Kantelip B, Reiter RE, Chopin DK, Thiery JP, Monnien F, Bittard H, Wallerand H, et al. The expression of twist has an impact on survival in human bladder cancer and is influenced by the smoking status. Urol Oncol. 2009;27(3):268–76. https://doi.org/10.1016/j.urolonc.2007.12.012.CrossRefPubMed

38.

Niu RF, Zhang L, Xi GM, Wei XY, Yang Y, Shi YR, Hao XS. Up-regulation of twist induces angiogenesis and correlates with metastasis in hepatocellular carcinoma. J Exp Clin Cancer Res. 2007;26(3):385–94.PubMed

39.

Rasti A, Madjd Z, Abolhasani M, Mehrazma M, Janani L, Saeednejad Zanjani L, Asgari M, et al. Cytoplasmic expression of Twist1, an EMT-related transcription factor, is associated with higher grades renal cell carcinomas and worse progression-free survival in clear cell renal cell carcinoma. Clin Exp Med. 2018;18(2):177–90. https://doi.org/10.1007/s10238-017-0481-2.CrossRefPubMed

40.

Yang Y, Wang G, Zhu D, Huang Y, Luo Y, Su P, Chen X, Wang Q, et al. Epithelial-mesenchymal transition and cancer stem cell-like phenotype induced by Twist1 contribute to acquired resistance to irinotecan in colon cancer. Int J Oncol. 2017;51(2):515–24. https://doi.org/10.3892/ijo.2017.4044.CrossRefPubMed

41.

Nguyen LV, Vanner R, Dirks P, Eaves CJ. Cancer stem cells: an evolving concept. Nat Rev Cancer. 2012;12(2):133–43. https://doi.org/10.1038/nrc3184.CrossRefPubMed

42.

Ayob AZ, Ramasamy TS. Cancer stem cells as key drivers of tumour progression. J Biomed Sci. 2018;25(1):20. https://doi.org/10.1186/s12929-018-0426-4.CrossRefPubMedPubMedCentral

43.

Mohammed AS, Kandil MA, Asaad NY, Aiad HA, El Tahmoudy MA, Hemida AS. Immunohistochemical expression of Twist in colorectal carcinoma. Menoufia Med J. 2015;28(3):725–33. https://doi.org/10.4103/1110-2098.165816.

44.

Hong R, Lim S-C. Overexpression of twist in colorectal adenocarcinoma. Basic Appl Pathol. 2009;2(1):15–20. https://doi.org/10.1111/j.1755-9294.2009.01030.x.CrossRef

45.

Celesti G, Di Caro G, Bianchi P, Grizzi F, Basso G, Marchesi F, et al. Presence of Twist1-positive neoplastic cells in the stroma of chromosome-unstable colorectal tumors. Gastroenterology. 2013;145(3):647–57 e15. https://doi.org/10.1053/j.gastro.2013.05.011.CrossRefPubMed

46.

Yusup A, Huji B, Fang C, Wang F, Dadihan T, Wang HJ, Upur H, et al. Expression of trefoil factors and TWIST1 in colorectal cancer and their correlation with metastatic potential and prognosis. World J Gastroenterol. 2017;23(1):110–20. https://doi.org/10.3748/wjg.v23.i1.110.CrossRefPubMedPubMedCentral

47.

Kim YH, Kim G, Kwon CI, Kim JW, Park PW, Hahm KB. TWIST1 and SNAI1 as markers of poor prognosis in human colorectal cancer are associated with the expression of ALDH1 and TGF-beta1. Oncol Rep. 2014;31(3):1380–8. https://doi.org/10.3892/or.2014.2970.CrossRefPubMed

48.

Gomez I, Pena C, Herrera M, Munoz C, Larriba MJ, Garcia V, et al. TWIST1 is expressed in colorectal carcinomas and predicts patient survival. PLoS One. 2011;6(3):e18023. https://doi.org/10.1371/journal.pone.0018023.CrossRefPubMedPubMedCentral

49.

Qin Q, Xu Y, He T, Qin C, Xu J. Normal and disease-related biological functions of Twist1 and underlying molecular mechanisms. Cell Res. 2012;22(1):90–106. https://doi.org/10.1038/cr.2011.144.CrossRefPubMed

50.

Dragoi D, Krattenmacher A, Mishra VK, Schmidt JM, Kloos UJ, Meixner LK, Hauck SM, Buggenthin F, Schwartz D, Marr C, Johnsen SA, Scheel CH, et al. Twist1 induces distinct cell states depending on TGFBR1-activation. Oncotarget. 2016;7(21):30396–407. https://doi.org/10.18632/oncotarget.8878.CrossRefPubMedPubMedCentral

51.

Liu S, Chen S, Zeng J. TGFbeta signaling: a complex role in tumorigenesis (review). Mol Med Rep. 2018;17(1):699–704. https://doi.org/10.3892/mmr.2017.7970.CrossRefPubMed

52.

Lichner Z, Saleh C, Subramaniam V, Seivwright A, Prud'homme GJ, Yousef GM. miR-17 inhibition enhances the formation of kidney cancer spheres with stem cell/ tumor initiating cell properties. Oncotarget. 2015;6(8):5567–81. https://doi.org/10.18632/oncotarget.1901.CrossRefPubMed

53.

Jung I, Gurzu S, Raica M, Cimpean AM, Szentirmay Z. The differences between the endothelial area marked with CD31 and CD105 in colorectal carcinomas by computer-assisted morphometrical analysis. Romanian J Morphol Embryol. 2009;50(2):239–43.

54.

Dallas NA, Samuel S, Xia L, Fan F, Gray MJ, Lim SJ, Ellis LM. Endoglin (CD105): a marker of tumor vasculature and potential target for therapy. Clin Cancer Res. 2008;14(7):1931–7. https://doi.org/10.1158/1078-0432.CCR-07-4478.CrossRefPubMed

55.

Martinovic Z, Kovac D, Martinovic M. Prognostic significance of microvessel density determining by Endoglin in stage II rectal carcinoma: a retrospective analysis. Gastroenterol Res Pract. 2015:504179.

56.

Zhang J, Yuan B, Zhang H, Li H. Human epithelial ovarian cancer cells expressing CD105, CD44 and CD106 surface markers exhibit increased invasive capacity and drug resistance. Oncol Lett. 2019;17(6):5351–60. https://doi.org/10.3892/ol.2019.10221.CrossRefPubMedPubMedCentral

57.

Bussolati B, Bruno S, Grange C, Ferrando U, Camussi G. Identification of a tumor-initiating stem cell population in human renal carcinomas. FASEB J. 2008;22(10):3696–705. https://doi.org/10.1096/fj.08-102590.CrossRefPubMed

58.

Hu J, Guan W, Liu P, Dai J, Tang K, Xiao H, Qian Y, Sharrow AC, Ye Z, Wu L, Xu H, et al. Endoglin is essential for the maintenance of self-renewal and Chemoresistance in renal Cancer stem cells. Stem Cell Rep. 2017;9(2):464–77. https://doi.org/10.1016/j.stemcr.2017.07.009.CrossRef

Title: Expressions of TWIST1 and CD105 markers in colorectal cancer patients and their association with metastatic potential and prognosis
Authors: Fahimeh Fattahi
Leili Saeednejad Zanjani
Somayeh Vafaei
Zohreh Habibi Shams
Jafar Kiani
Marzieh Naseri
Elmira Gheytanchi
Zahra Madjd
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Metastasis
Colorectal Cancer
Colorectal Cancer
Published in: Diagnostic Pathology / Issue 1/2021
Electronic ISSN: 1746-1596
DOI: https://doi.org/10.1186/s13000-021-01088-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Expressions of TWIST1 and CD105 markers in colorectal cancer patients and their association with metastatic potential and prognosis

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Aurora-A kinase is differentially expressed in the nucleus and cytoplasm in normal Müllerian epithelium and benign, borderline and malignant serous ovarian neoplasms

Transmission of synovial sarcoma from a single multi-organ donor to three transplant recipients: case report

Accuracy of HPV E6/E7 mRNA examination using in situ hybridization in diagnosing cervical intraepithelial lesions

SWI/SNF-deficient undifferentiated/rhabdoid carcinoma of the gallbladder carrying a POLE mutation in a 30-year-old woman: a case report

Giant vascular eccrine spiradenoma: the first case in the scrotum and review of the literature author

Long non-coding RNA DUXAP8 elevates RCN2 expression and facilitates cell malignant behaviors and angiogenesis in cervical cancer via sponging miR-1297