Sublingual Nodules: Diagnostic Markers of Metastatic Breast Cancer

  • Xue Yang
  • Cui-hong Zhu
  • Rui Cao
  • Jian Hao
  • Xiong-zhi Wu
Original Article



To evaluate the diagnostic significance of sublingual nodules for metastasis of patients with breast cancer and further to explore the mechanisms of sublingual nodules.


The image data of 117 in-patients with breast cancer in stage I–IV in Tianjin Medical University Cancer Institute and Hospital from December 2009 to September 2011 were assessed retrospectively. All photos of patients’ tongue were recorded by the digital camera of uniform type within 1 month after serological examination and regular re-examined by computed tomography (CT), magnetic resonance imaging and positron emission tomography CT. The presence of sublingual nodules was the positive standard. Chi square test and two-independent-sample test were used to determine the diagnostic value between the status of sublingual nodules and Clinico-pathological characteristics. The optimal cut-off of uric acid (UA) level to diagnose sublingual nodules was determined by receiver operating curve (ROC) analysis.


Breast cancer patients with sublingual nodules had a higher risk of recurrence and/or metastasis than patients without it (P<0.001). Sublingual nodules was significantly correlated with increased serum UA level (P=0.001). The optimal cut-off value of UA level to diagnose sublingual nodules was 290 μmol/L. Furthermore, the elevated serum UA level (⩾290 μmol/L) was significantly related to breast cancer recurrence and/or metastasis (P<0.001).


Sublingual nodules were potential diagnostic markers for metastatic breast cancer. The formation of sublingual nodules was associated with elevated level of serum UA.


breast cancer sublingual nodule metastasis recurrence serum uric acid Chinese medicine diagnosis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    DeSantis C, Siegel R, Bandi P, Jemal A. Breast cancer statistics, 2011. CA Cancer J Clin 2011;61:409–418.CrossRefPubMedGoogle Scholar
  2. 2.
    Doherty MK, Morris PG. Eribulin for the treatment of metastatic breast cancer: an update on its safety and efficacy. Int J Womens Health 2015;7:47–58.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Liu Y, Ji R, Li J, Gu Q, Zhao X, Sun T, et al. Correlation effect of EGFR and CXCR4 and CCR7 chemokine receptors in predicting breast cancer metastasis and prognosis. J Exp Clin Cancer Res 2010;29:16.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Sofi AA, Mohamed I, Koumaya M, Kamaluddin Z. Local therapy in metastatic breast cancer is associated with improved survival. Am J Ther 2013;20:487–492.CrossRefPubMedGoogle Scholar
  5. 5.
    Costelloe CM, Rohren EM, Madewell JE, Hamaoka T, Theriault RL, Yu TK, et al. Imaging bone metastases in breast cancer: techniques and recommendations for diagnosis. Lancet Oncol 2009;10:606–614.CrossRefPubMedGoogle Scholar
  6. 6.
    Cardoso F, Harbeck N, ESMO Guidelines Working Group. Locally recurrent or metastatic breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2009;20 Suppl 4:iv15–18.Google Scholar
  7. 7.
    Clevert DA, Jung EM, Stock KF, Weckbach S, Feuerbach S, Reiser M, et al. Evaluation of malignant liver tumors: biphasic MS-CT versus quantitative contrast harmonic imaging ultrasound. Z Gastroenterol 2009;47:1195–1202.CrossRefPubMedGoogle Scholar
  8. 8.
    Berman CG, Clark RA. Diagnostic imaging in cancer. Primary Care 1992;19:677–713.PubMedGoogle Scholar
  9. 9.
    Cheung K, Graves C, Robertson J. Tumour marker measurements in the diagnosis and monitoring of breast cancer. Cancer Treat Rev 2000;26:91–102.CrossRefPubMedGoogle Scholar
  10. 10.
    Tampellini M, Berruti A, Gerbino A, Buniva T, Torta M, Gorzegno G, et al. Relationship between CA 15-3 serum levels and disease extent in predicting overall survival of breast cancer patients with newly diagnosed metastatic disease. Brit J Cancer 1997;75:698–702.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Jiang B, Liang X, Chen Y, Ma T, Liu L, Li J, et al. Integrating next-generation sequencing and traditional tongue diagnosis to determine tongue coating microbiome. Sci Rep 2012;2:936.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Kim J, Han G, Ko SJ, Nam DH, Park JW, Ryu B, et al. Tongue diagnosis system for quantitative assessment of tongue coating in patients with functional dyspepsia: a clinical trial. J Ethnopharmacol 2014;155:709–713.CrossRefPubMedGoogle Scholar
  13. 13.
    Liu S, Hua YQ, Sun ZP, Tan S, Lu DM. Breast cancer pathogenesis of stagnation of phlegm, poison and blood stasis: rationale and clinical application in traditional Chinese medicine. Chin J Integr Med 2007;5:122–125.CrossRefGoogle Scholar
  14. 14.
    Stotz M, Szkandera J, Seidel J, Stojakovic T, Samonigg H, Reitz D, et al. Evaluation of uric acid as a prognostic bloodbased marker in a large cohort of pancreatic cancer patients. PloS One 2014;9:e104730.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Osgood K, Krakoff J, Thearle M. Serum uric acid predicts both current and future components of the metabolic syndrome. Metab Syndr Relat 2013;11:157–162.CrossRefGoogle Scholar
  16. 16.
    Yoo TW, Sung KC, Shin HS, Kim BJ, Kim BS, Kang JH, et al. Relationship between serum uric acid concentration and insulin resistance and metabolic syndrome. Circ J 2005;69:928–933.CrossRefPubMedGoogle Scholar
  17. 17.
    Fini MA, Elias A, Johnson RJ, Wright RM. Contribution of uric acid to cancer risk, recurrence, and mortality. Clin Transl Med 2012;1:16.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Edge SB. AJCC cancer staging manual. JAMA 2010;304:1726–1727.CrossRefGoogle Scholar
  19. 19.
    Lo LC, Cheng TL, Chen YJ, Natsagdorj S, Chiang JY. TCM tongue diagnosis index of early-stage breast cancer. Complement Ther Med 2015;23:705–713.CrossRefPubMedGoogle Scholar
  20. 20.
    Liu Q, Yue XQ, Deng WZ, Ren RZ. Quantitative study on tongue color in primary liver cancer patients by analysis system for comprehensive information of tongue diagnosis. Chin J Integr Med 2003;1:180–183.CrossRefGoogle Scholar
  21. 21.
    Cao R, Wang LP, Chi JD, Wu XZ. Nodule and eminence on frenulum labii superioris: diagnostic markers for metastatic colorectal cancer. Chin J Integr Med 2014;20:416–419.CrossRefPubMedGoogle Scholar
  22. 22.
    Pang B, Zhang D, Wang K. Tongue image analysis for appendicitis diagnosis. Inform Sci 2005;175:160–176.CrossRefGoogle Scholar
  23. 23.
    Hao J, Zhu C, Cao R, Yang X, Ding X, Man Y, et al. Purple-bluish tongue is associated with platelet counts, and the recurrence of epithelial ovarian cancer. J Tradit Chin Med 2016;36:321–325.CrossRefPubMedGoogle Scholar
  24. 24.
    Kong D, Wang Y, Liu Y, Zhang Z, Liu G, Qi W, et al. The association between blood lipid and phlegm turbidity syndrome of angina pectoris: a systematic review and meta-analysis. Complement Ther Med 2014;22:801–813.CrossRefPubMedGoogle Scholar
  25. 25.
    Boffetta P, Nordenvall C, Nyrén O, Ye W. A prospective study of gout and cancer. Eur J Cancer Prev 2009;18:127–132.CrossRefPubMedGoogle Scholar
  26. 26.
    Ruggiero C, Cherubini A, Ble A, Bos AJ, Maggio M, Dixit VD, et al. Uric acid and inflammatory markers. Eur Heart J 2006;27:1174–1181.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Netea MG, Kullberg BJ, Blok WL, Netea RT, van der Meer JW. The role of hyperuricemia in the increased cytokine production after lipopolysaccharide challenge in neutropenic mice. Blood 1997;89:577–582.PubMedGoogle Scholar
  28. 28.
    Coussens LM, Werb Z. Inflammation and cancer. Nature 2002;420:860–867.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 2001;357:539–545.CrossRefPubMedGoogle Scholar

Copyright information

© Chinese Association of the Integration of Traditional and Western Medicine 2018

Authors and Affiliations

  • Xue Yang
    • 1
    • 2
  • Cui-hong Zhu
    • 3
  • Rui Cao
    • 1
  • Jian Hao
    • 1
  • Xiong-zhi Wu
    • 1
  1. 1.Tianjin Medical University Cancer Institute and Hospital, National Clinical Center for Cancer, Key Laboratory of Cancer Prevention and TherapyTianjinChina
  2. 2.Department of Medical OncologyTianjin Medical Universty General HospitalTianjinChina
  3. 3.Zhong-Shan-Men In-patient DepartmentTianjin Medical University Cancer Institute and HospitalTianjinChina

Personalised recommendations