Surgery Today

, Volume 49, Issue 2, pp 158–169 | Cite as

BRF2 as a promising indicator for radical lymph-node dissection surgery in patients with cN0 squamous cell carcinoma of the middle thoracic esophagus

  • Yu Tian
  • Cong Wang
  • Ming LuEmail author
Original Article



Radical lymph-node dissection surgery in patients with cN0 middle thoracic esophageal squamous cell carcinoma (ESCC) remains controversial. We sought a novel biomarker that could be used for decision-making in relation to radical lymph-node dissection.


One hundred and nineteen patients with cN0 middle thoracic ESCC undergoing three-field lymph-node dissection (3FLND) or two-field lymph-node dissection (Ivor Lewis) esophagectomy were reviewed. A survival analysis, and Chi-square and parametric tests were performed.


A Cox regression analysis revealed that the expression of BRF2 was an independent prognostic factor for overall survival (P = 0.014) and progression-free survival (P = 0.014). The survival of patients who underwent 3FLND was better than that of patients who underwent Ivor Lewis esophagectomy in the BRF2 overexpression group (P = 0.002), but not in the BRF2 nonoverexpression group (P = 0.386). The risk of lymph-node recurrence and the number of recurrent lymph nodes in patients with the overexpression of BRF2 were increased in the Ivor Lewis group in comparison to the 3FLND group (P = 0.01 and P < 0.001). The risk of cervical and superior mediastinal lymph-node recurrence was positively correlated with the overexpression of BRF2 (P = 0.027). Furthermore, in the Ivor Lewis group, a significant correlation was found between the risk of lymph-node recurrence or the number of recurrent lymph nodes and the expression of BRF2 (P = 0.002 and P = 0.004), but not in the 3FLND group (P = 0.193 and P = 0.694).


3FLND generated better survival outcomes and reduced the rate of lymph-node recurrence in comparison to Ivor Lewis in patients with the overexpression of BRF2. BRF2 can be used as an indicator for radical lymph-node dissection surgery in cN0 ESCC patients.


BRF2 Esophageal squamous cell cancer 3FLND Ivor Lewis 



TFIIB-related factor 2


Esophageal squamous cell cancer


Three-field lymph-node dissection esophagectomy

Ivor Lewis

Two-field lymph-node dissection esophagectomy


Overall survival


Progression-free survival



This work was supported by National Natural Science Foundation of Shandong Province (ZR2017PH018).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest in association with the present study.


  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer Statistics. CA. 2017;67:7–30.PubMedGoogle Scholar
  2. 2.
    Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, et al. Cancer statistics in China, 2015. CA. 2016;66:115–32.PubMedGoogle Scholar
  3. 3.
    Ren Y, Cao B, Law S, Xie Y, Lee PY, Cheung L, et al. Hepatocyte growth factor promotes cancer cell migration and angiogenic factors expression: a prognostic marker of human esophageal squamous cell carcinomas. Clin Cancer Res. 2005;11:6190–7.CrossRefGoogle Scholar
  4. 4.
    Mariette C, Balon JM, Piessen G, Fabre S, Van Seuningen I, Triboulet JP. Pattern of recurrence following complete resection of esophageal carcinoma and factors predictive of recurrent disease. Cancer. 2003;97:1616–23.CrossRefGoogle Scholar
  5. 5.
    Nakagawa S, Kanda T, Kosugi S, Ohashi M, Suzuki T, Hatakeyama K. Recurrence pattern of squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with three-field lymphadenectomy. J Am Coll Surg. 2004;198:205–11.CrossRefGoogle Scholar
  6. 6.
    Ding Y, Shimada Y, Maeda M, Kawabe A, Kaganoi J, Komoto I, et al. Association of CC chemokine receptor 7 with lymph node metastasis of esophageal squamous cell carcinoma. Clin Cancer Res. 2003;9:3406–12.PubMedGoogle Scholar
  7. 7.
    Kato K, Hida Y, Miyamoto M, Hashida H, Shinohara T, Itoh T, et al. Overexpression of caveolin-1 in esophageal squamous cell carcinoma correlates with lymph node metastasis and pathologic stage. Cancer. 2002;94:929–33.CrossRefGoogle Scholar
  8. 8.
    Kawakita Y, Motoyama S, Sato Y, Koyota S, Wakita A, Liu J, et al. Sphingosine-1-phosphate/sphingosine kinase 1-dependent lymph node metastasis in esophageal squamous cell carcinoma. Surgery today. 2017;47(11):1312–20.CrossRefGoogle Scholar
  9. 9.
    Geiduschek EP, Kassavetis GA. The RNA polymerase III transcription apparatus. J Mol Biol. 2001;310:1–26.CrossRefGoogle Scholar
  10. 10.
    Cabarcas S, Jacob J, Veras I, Schramm L. Differential expression of the TFIIIB subunits Brf1 and Brf2 in cancer cells. BMC Mol Biol. 2008;9:74.CrossRefGoogle Scholar
  11. 11.
    Cabarcas S, Schramm L. RNA polymerase III transcription in cancer: the BRF2 connection. Mol Cancer. 2011;10:47.CrossRefGoogle Scholar
  12. 12.
    Lockwood WW, Chari R, Coe BP, Thu KL, Garnis C, Malloff CA, et al. Integrative genomic analyses identify BRF2 as a novel lineage-specific oncogene in lung squamous cell carcinoma. PLoS Med. 2010;7:e1000315.CrossRefGoogle Scholar
  13. 13.
    Tian Y, Lu M, Yue W, Li L, Li S, Gao C, et al. TFIIB-related factor 2 is associated with poor prognosis of nonsmall cell lung cancer patients through promoting tumor epithelial-mesenchymal transition. BioMed Res Int. 2014;2014:530786.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Lu M, Tian H, Yue W, Li L, Li S, Qi L, et al. TFIIB-related factor 2 over expression is a prognosis marker for early-stage non-small cell lung cancer correlated with tumor angiogenesis. PloS one. 2014;9:e88032.CrossRefGoogle Scholar
  15. 15.
    Lu M, Tian H, Yue W, Li L, Li S, Qi L, et al. Overexpression of TFIIB-related factor 2 is significantly correlated with tumor angiogenesis and poor survival in patients with esophageal squamous cell cancer. Med Oncol. 2013;30:553.CrossRefGoogle Scholar
  16. 16.
    Lewis I. The surgical treatment of carcinoma of the oesophagus; with special reference to a new operation for growths of the middle third. Br J Surg. 1946;34:18–31.CrossRefGoogle Scholar
  17. 17.
    Bhansali MS, Fujita H, Kakegawa T, Yamana H, Ono T, Hikita S, et al. Pattern of recurrence after extended radical esophagectomy with three-field lymph node dissection for squamous cell carcinoma in the thoracic esophagus. World J Surg. 1997;21:275–81.CrossRefGoogle Scholar
  18. 18.
    Chen G, Wang Z, Liu XY, Liu FY. Recurrence pattern of squamous cell carcinoma in the middle thoracic esophagus after modified Ivor-Lewis esophagectomy. World J Surg. 2007;31:1107–14.PubMedGoogle Scholar
  19. 19.
    Wolf D, Wolf AM, Rumpold H, Fiegl H, Zeimet AG, Muller-Holzner E, et al. The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res. 2005;11:8326–31.CrossRefGoogle Scholar
  20. 20.
    Li SH, Tian H, Yue WM, Li L, Li WJ, Chen ZT, et al. Overexpression of metastasis-associated protein 1 is significantly correlated with tumor angiogenesis and poor survival in patients with early-stage non-small cell lung cancer. Ann Surg Oncol. 2011;18:2048–56.CrossRefGoogle Scholar
  21. 21.
    Cai WJ, Xin PL. Pattern of relapse in surgical treated patients with thoracic esophageal squamous cell carcinoma and its possible impact on target delineation for postoperative radiotherapy. Radiother Oncol. 2010;96:104–7.CrossRefGoogle Scholar
  22. 22.
    Nishimaki T, Tanaka O, Suzuki T, Aizawa K, Hatakeyama K, Muto T. Patterns of lymphatic spread in thoracic esophageal cancer. Cancer. 1994;74:4–11.CrossRefGoogle Scholar
  23. 23.
    Stein HJ, Feith M, Bruecher BL, Naehrig J, Sarbia M, Siewert JR. Early esophageal cancer: pattern of lymphatic spread and prognostic factors for long-term survival after surgical resection. Ann Surg. 2005;242:566 – 73 (discussion 73–5).PubMedPubMedCentralGoogle Scholar
  24. 24.
    Martin DJ, Church NG, Kennedy CW, Falk GL. Does systematic 2-field lymphadenectomy for esophageal malignancy offer a survival advantage? Results from 178 consecutive patients. Dis Esophagus. 2008;21:612–8.CrossRefGoogle Scholar
  25. 25.
    Nishihira T, Hirayama K, Mori S. A prospective randomized trial of extended cervical and superior mediastinal lymphadenectomy for carcinoma of the thoracic esophagus. Am J Surg. 1998;175:47–51.CrossRefGoogle Scholar
  26. 26.
    Gouge J, Vannini A. New tricks for an old dog: Brf2-dependent RNA Polymerase III transcription in oxidative stress and cancer. Transcription. 2018;9(1):61–6.CrossRefGoogle Scholar
  27. 27.
    Gouge J, Satia K, Guthertz N, Widya M, Thompson AJ, Cousin P, et al. Redox signaling by the RNA polymerase III TFIIB-related factor Brf2. Cell. 2015;163(6):1375–87.CrossRefGoogle Scholar
  28. 28.
    Wang L, Qu J, Zhou L, Liao F, Wang J. MicroRNA-373 inhibits cell proliferation and invasion via targeting BRF2 in human non-small cell lung cancer A549 cell line. Cancer Res Treat. 2018;50(3):936–949.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of Thoracic SurgeryThe Second Hospital of Shandong UniversityJinanPeople’s Republic of China
  2. 2.Department of Radiation Oncology, Qilu HospitalShandong UniversityJinanPeople’s Republic of China
  3. 3.Department of Thoracic Surgery, Qilu HospitalShandong UniversityJinanPeople’s Republic of China

Personalised recommendations