Skip to main content
  • Original article
  • Open access
  • Published:

Metabolic syndrome is associated with better prognosis in patients with tongue squamous cell carcinoma



Metabolic syndrome (MS) is associated with several cancers, but it is not clear whether MS affects the prognosis of tongue squamous cell carcinoma (TSCC). This study aimed to evaluate the prognostic value of MS in TSCC.


Clinical data from 252 patients with TSCC who were initially treated at the Sun Yat-sen University Cancer Center between April 1998 and June 2011 were collected, and the associations between MS and clinicopathologic factors were retrospectively analyzed. Prognostic outcomes were examined by Kaplan-Meier analysis and Cox regression analysis.


Of the 252 patients, 48 were diagnosed with MS. MS was associated with early N category in TSCC (P < 0.001). The patients with MS showed longer survival than those without MS (P = 0.028). MS was an independent prognostic factor for patients with TSCC.


MS is associated with early N category in TSCC. It is an independent prognostic factor for better survival in patients with TSCC.


Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide. OSCC accounts for over 90% of all oral cancers [1], and the most common location for this disease is the tongue [2]. Tongue squamous cell carcinoma (TSCC) is especially prevalent in low-income communities in North France, East Europe, South America, and Southeast Asia, and 90% of patients with TSCC are over 45 years old [3]. TSCC seriously affects quality of life of the patients and carries a poor prognosis, with a 5-year overall survival (OS) rate of 56% [4].

Metabolic syndrome (MS) is a cluster of metabolic abnormalities. The pathophysiologic basis of MS is insulin resistance [5]. The diagnosis criteria for MS include central obesity, hyperglycemia, hypertriglyceridemia, hypertension, and low serum concentration of high-density lipoprotein (HDL) [6]. MS is related to several cancers, including breast cancer, prostate cancer, and gastric cancer. MS and its components are associated with worse survival in breast cancer [7] and prostate cancer [8], but better survival for gastric cancer [9]. Obesity was reported to be an adverse independent prognostic factor for early-stage TSCC [10]. However, there is little information regarding the association between MS and TSCC or the impact of MS on TSCC patient survival. In this study, we tried to analyze whether the status of MS before treatment have any impact on the OS in patients with TSCC.


Patient selection

A total of 252 patients diagnosed with TSCC who were initially treated at the Sun Yat-sen University Cancer Center between April 1998 and June 2011 were involved in this study, including 145 males (58%) and 107 females (42%). Subject ages ranged from 20 to 89 years, with a median age of 52 years. None of these patients had distant metastasis before treatment. All patients underwent surgery; 59 (23%) underwent multimodality therapy including surgery. Surgical margins were tumor-free for all patients. The data regarding MS and its components were recorded before treatment. The OS was defined as the duration from the date of initial treatment to the date of death or the last follow-up (July 2014). This study followed the Declaration of Helsinki for medical protocol and ethics. Study approval was obtained from independent ethics committees at Cancer Center of Sun Yat-Sen University.

Diagnosis criteria of MS

According to the National Cholesterol Education Program’s Adult Treatment Panel III, our diagnosis criteria of MS included (1) fasting plasma glucose (GLU) ≥6.1 mmol/L or a diagnosis of diabetes; (2) abdominal obesity, with a body mass index (BMI) ≥25 kg/m2; (3) triglycerides (TG) ≥1.7 mmol/L; (4) high-density lipoprotein (HDL) ≤1.04 mmol/L for males and ≤1.3 mmol/L for females; and (5) hypertension, with the systolic blood pressure (BP) ≥130/80 mmHg. Meeting 3 or more of the criteria was necessary for diagnosis [9].

Statistical analyses

The chi-square test was performed to analyze the relationship between MS and clinicopathologic factors of TSCC. Kaplan-Meier and log-rank tests were used for survival analysis. Multivariate Cox regression analysis was performed for significant variables identified by using univariate analysis. SPSS 16.0 software was used for all analyses. A P value of <0.05 was considered statistically significant.


Association between MS and clinicopathologic characteristics of TSCC

The clinicopathologic characteristics of 252 patients are shown in Table 1. Of these patients, 48 (19.1%) were diagnosed with MS. MS was associated with early N category (P < 0.001). However, there was no association between MS and age, gender, T stage, pathologic grade, treatment strategy, or tumor location.

Table 1 Association between MS and clinicopathologic characteristics of patients with TSCC

Relationship between MS and survival of TSCC patients

At the time of the last follow-up, 184 patients (73.0%) were alive, and 68 (27.0%) died of cancer-related diseases. Figure 1 demonstrates that the patients with MS had better OS than those without MS (P = 0.028). The Cox proportional hazards model was used to verify whether MS and other variables were independent prognostic factors for TSCC patients. The univariate analysis results showed that MS, sex, age, T category, N category, pathologic grade, and treatment strategy were associated with OS. Multivariate Cox regression analysis revealed that MS, age, T category, N category, pathologic grade, and treatment strategy were independent prognostic factors for patients with TSCC (Table 2).

Figure 1
figure 1

Overall survival curves for patients with tongue squamous cell carcinoma (TSCC) according to the status of metabolic syndrome (MS). Kaplan-Meier analysis results indicate that patients with MS have better overall survival than those without MS (P = 0.028).

Table 2 Univariate and multivariate Cox regression analyses for overall survival in patients with TSCC


Our study demonstrated that MS was associated with early N category in TSCC. In addition, MS was an independent prognostic factor for better survival in patients with TSCC.

This study first reported the association of MS with early N category in TSCC. Previous reports demonstrated that MS was associated with better differentiation in gastric cancer cells [9], whereas others indicated that MS or its components were associated with a more aggressive tumor type in colon cancer and prostate cancer [11,12]; the influence of MS on breast cancer remains controversial [13,14]. The mechanism by which MS influences N category is not well understood. Insulin receptor and insulin-like growth factor 1 (IGF-1) are expressed in most cancer cells, and IGF-1 can stimulate invasion and proliferation of cervical cancer cells [15]. The patients with diabetes had low concentrations of IGF-1 [16]. Moreover, the insulin receptor-activating signaling pathways may offer protection from invasion and metastasis of cancer cells [17,18]; however, the mechanism remains unclear and requires further investigation. In addition, underweight patients in China were associated with lower income and education, and they were less likely to receive the correct treatment when diagnosed with an early-stage disease. The TNM classification significantly affects tongue cancer prognosis; the earlier the classification, the better the prognosis. In our study, T category and N category were independent prognostic factors for patients with TSCC. Liu et al. [19] reported that the 5-year OS rates for patients with stages I, II, III, and IV oral cancers were 79.8%, 68.2%, 57.2%, and 50.4%, respectively. Thus, it is critical to diagnose tongue cancer in early stages [3]. In addition, the pathologic grade significantly affects prognosis of the patients. The patients who underwent multimodality therapy in our study usually had late-stage disease, which leaded to worse prognosis of these patients.

The impact of MS on cancer patient prognosis, including cervical cancer, remains controversial. For example, MS predicts poor survival in patients with prostate cancer and breast cancer [7,8], whereas Wei et al. [9] reported that old patients with early-stage gastric cancer and MS had a better prognosis. In patients with early-stage colon cancer, diabetes and hypertension predicted poor survival, but dyslipidemia predicted good survival [20,21]. Another study reported increased odds of MS among American women with a history of cervical cancer, but no association was observed between the single component of MS and cervical cancer [22]. Several reports suggested that leanness might be associated with poor outcome for patients with cervical cancer [19,23-26]. However, obesity was considered an independent predictor of increased risk of death in patients with early-stage tongue cancer [10]. However, patients in these studies had various tumor sites and different pathologic diagnoses. In addition, some of these studies were limited by small sample sizes. Our study found that MS was associated with better prognosis in patients with TSCC. Malnutrition is common in patients with head and neck cancer, especially in oral tongue cancer, which seriously affects the patient’s nutritional status, so weight loss before treatment was associated with poor prognosis. In addition, patients without MS are more likely to suffer from nutritional deficiency, which may lead to poor prognosis. Good nutritional status could improve survival by strengthening immunity and providing high tolerance for lengthy therapeutic periods. A retrospective research of oral cavity cancer and oropharyngeal cancer showed that weight loss was a strong predictor of death [19,24,26]. Another study also reported poor survival in oral cancer patients with a BMI < 22.8 kg/m2 before surgery [19].

Several individual components of MS have been recognized as carcinogenic. However, our research did not identify any significant influence of MS components on TSCC prognosis. This result was similar to those of previous studies [9,22]. Epidemiologic studies indicated that clustering MS components increased the carcinogenic effect on colorectal cancer development and mortality compared with individual factors [27,28]. Our findings align with this theory of synergism among MS components, as none of the individual MS components was associated with TSCC, but when clustering at least 3 components, this association became significant and remained significant when adjusting for other risk factors for TSCC. Further investigations are needed to better understand the effects of MS and its components on survival in TSCC patients.

The molecular and cellular mechanisms by which MS affects cancer patient survival are very complicated. Smith et al. [29] reported that IGF-1 is a potential pathway linking the environment with cancer. High levels of IGF-1 increases the risk of cancer and aggressiveness of malignancies. Cowey et al. [30] reported that TG promoted cancer cell proliferation and showed anti-apoptotic activity due to the generation of reactive oxygen species (ROS) and oxidative stress, which cause DNA damage. Obesity is linked with higher incidence and mortality of several cancers, but there are still some opposing opinions [10,19,23,24,26]. Levels of adipokine, leptin, and adiponectin in obesity can affect several signal transduction pathways involved in cell survival [31], and Shin et al. [32] reported that the adiponectin receptor is related to gastric cancer development, progression, and poor survival. BMI influences cancers by releasing several inflammatory mediators, such as tumor necrosis factor alpha, interleukin-6, and prostaglandin E2 [33]. A previous study reported an association between cervical cancer and low HDL levels [22].

Our study had some limitations. First, it was a retrospective study. Second, this study did not include disease-free survival due to limited clinical data. Third, we did not know the exact time of the occurrence of MS, which may lead to an overestimation of the associations.


In conclusion, this study first demonstrated that MS is associated with early N category and predicts good prognosis in patients with TSCC. Understanding the underlie molecular and cellular mechanisms may provide clues to prevent cancer development. Similarly, therapeutic interventions targeting these molecular mechanisms might manifest a positive perspective for the treatment of TSCC. In addition, our results indicate that good nutritional status may improve survival in patients with TSCC.


Written informed consent was obtained from the patient for the publication of this report and any accompanying images.


  1. Chen YK, Huang HC, Lin LM, Lin CC. Primary oral squamous cell carcinoma: an analysis of 703 cases in southern Taiwan. Oral Oncol. 1999;35:173–9.

    CAS  PubMed  Google Scholar 

  2. Hirata RM, Jaques DA, Chambers RG, Tuttle JR, Mahoney WD. Carcinoma of the oral cavity. An analysis of 478 cases. Ann Surg. 1975;182:98–103.

    PubMed Central  CAS  PubMed  Google Scholar 

  3. Scully C, Bagan J. Oral squamous cell carcinoma overview. Oral Oncol. 2009;45:301–8.

    CAS  PubMed  Google Scholar 

  4. Bell RB, Kademani D, Homer L, Dierks EJ, Potter BE. Tongue cancer: is there a difference in survival compared with other subsites in the oral cavity? J Oral Maxillofac Surg. 2007;65:229–36.

    PubMed  Google Scholar 

  5. Ayturk S, Gursoy A, Kut A, Anil C, Nar A, Tutuncu NB. Metabolic syndrome and its components are associated with increased thyroid volume and nodule prevalence in a mild-to-moderate iodine-deficient area. Eur J Endocrinol. 2009;161:599–605.

    CAS  PubMed  Google Scholar 

  6. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120:1640–5.

    CAS  PubMed  Google Scholar 

  7. Reeves KW, McLaughlin V, Fredman L, Ensrud K, Cauley JA. Components of metabolic syndrome and risk of breast cancer by prognostic features in the study of osteoporotic fractures cohort. Cancer Causes Control. 2012;23:1241–51.

    PubMed Central  PubMed  Google Scholar 

  8. Ozbek E, Otunctemur A, Dursun M, Sahin S, Besiroglu H, Koklu I, et al. The metabolic syndrome is associated with more aggressive prostate cancer. Asian Pac J Cancer Prev. 2014;15:4029–32.

    PubMed  Google Scholar 

  9. Wei XL, Qiu MZ, Lin HX, Zhang Y, Liu JX, Yu HM, et al. Patients with old age or proximal tumors benefit from metabolic syndrome in early stage gastric cancer. PLoS One. 2014;9:e89965.

    PubMed Central  PubMed  Google Scholar 

  10. Iyengar NM, Kochhar A, Morris PG, Morris LG, Zhou XK, Ghossein RA, et al. Impact of obesity on the survival of patients with early-stage squamous cell carcinoma of the oral tongue. Cancer. 2014;120:983–91.

    PubMed Central  PubMed  Google Scholar 

  11. Xiang YZ, Xiong H, Cui ZL, Jiang SB, Xia QH, Zhao Y, et al. The association between metabolic syndrome and the risk of prostate cancer, high-grade prostate cancer, advanced prostate cancer, prostate cancer-specific mortality and biochemical recurrence. J Exp Clin Cancer Res. 2013;32:9.

    PubMed Central  PubMed  Google Scholar 

  12. Healy LA, Howard JM, Ryan AM, Beddy P, Mehigan B, Stephens R, et al. Metabolic syndrome and leptin are associated with adverse pathological features in male colorectal cancer patients. Colorectal Dis. 2012;14:157–65.

    CAS  PubMed  Google Scholar 

  13. Colonna SV, Douglas Case L, Lawrence JA. A retrospective review of the metabolic syndrome in women diagnosed with breast cancer and correlation with estrogen receptor. Breast Cancer Res Treat. 2012;131:325–31.

    CAS  PubMed  Google Scholar 

  14. Healy LA, Ryan AM, Carroll P, Ennis D, Crowley V, Boyle T, et al. Metabolic syndrome, central obesity and insulin resistance are associated with adverse pathological features in postmenopausal breast cancer. Clin Oncol (R Coll Radiol). 2010;22:281–8.

    CAS  Google Scholar 

  15. Shen MR, Hsu YM, Hsu KF, Chen YF, Tang MJ, Chou CY. Insulin-like growth factor 1 is a potent stimulator of cervical cancer cell invasiveness and proliferation that is modulated by alphavbeta3 integrin signaling. Carcinogenesis. 2006;27:962–71.

    CAS  PubMed  Google Scholar 

  16. van Dijk PR, Logtenberg SJ, Groenier KH, Kleefstra N, Bilo HJ, Arnqvist HJ. Effect of i.p. insulin administration on IGF1 and IGFBP1 in type 1 diabetes. Endocr Connect. 2014;3:17–23.

    PubMed Central  PubMed  Google Scholar 

  17. Zhang H, Pelzer AM, Kiang DT, Yee D. Down-regulation of type I insulin-like growth factor receptor increases sensitivity of breast cancer cells to insulin. Cancer Res. 2007;67:391–7.

    CAS  PubMed  Google Scholar 

  18. Mardilovich K, Pankratz SL, Shaw LM. Expression and function of the insulin receptor substrate proteins in cancer. Cell Commun Signal. 2009;7:14.

    PubMed Central  PubMed  Google Scholar 

  19. Liu SA, Tsai WC, Wong YK, Lin JC, Poon CK, Chao SY, et al. Nutritional factors and survival of patients with oral cancer. Head Neck. 2006;28:998–1007.

    PubMed  Google Scholar 

  20. Yang Y, Mauldin PD, Ebeling M, Hulsey TC, Liu B, Thomas MB, et al. Effect of metabolic syndrome and its components on recurrence and survival in colon cancer patients. Cancer. 2013;119:1512–20.

    PubMed  Google Scholar 

  21. Shen Z, Ye Y, Bin L, Yin M, Yang X, Jiang K, et al. Metabolic syndrome is an important factor for the evolution of prognosis of colorectal cancer: survival, recurrence, and liver metastasis. Am J Surg. 2010;200:59–63.

    PubMed  Google Scholar 

  22. Penaranda EK, Shokar N, Ortiz M. Relationship between metabolic syndrome and history of cervical cancer among a US national population. ISRN Oncol. 2013;2013:840964.

    PubMed Central  PubMed  Google Scholar 

  23. Gaudet MM, Olshan AF, Chuang SC, Berthiller J, Zhang ZF, Lissowska J, et al. Body mass index and risk of head and neck cancer in a pooled analysis of case–control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. Int J Epidemiol. 2010;39:1091–102.

    PubMed Central  PubMed  Google Scholar 

  24. Franceschi S, Dal Maso L, Levi F, Conti E, Talamini R, La Vecchia C. Leanness as early marker of cancer of the oral cavity and pharynx. Ann Oncol. 2001;12:331–6.

    CAS  PubMed  Google Scholar 

  25. Van Bokhorst-de Van der Schuer MA, Langendoen SI, Vondeling H, Kuik DJ, Quak JJ, Van Leeuwen PA. Perioperative enteral nutrition and quality of life of severely malnourished head and neck cancer patients: a randomized clinical trial. Clin Nutr. 2000;19:437–44.

    CAS  PubMed  Google Scholar 

  26. Nguyen TV, Yueh B. Weight loss predicts mortality after recurrent oral cavity and oropharyngeal carcinomas. Cancer. 2002;95:553–62.

    PubMed  Google Scholar 

  27. Colangelo LA, Gapstur SM, Gann PH, Dyer AR, Liu K. Colorectal cancer mortality and factors related to the insulin resistance syndrome. Cancer Epidemiol Biomarkers Prev. 2002;11:385–91.

    PubMed  Google Scholar 

  28. Trevisan M, Liu J, Muti P, Misciagna G, Menotti A, Fucci F, et al. Markers of insulin resistance and colorectal cancer mortality. Cancer Epidemiol Biomarkers Prev. 2001;10:937–41.

    CAS  PubMed  Google Scholar 

  29. Smith GD, Gunnell D, Holly J. Cancer and insulin-like growth factor-I. A potential mechanism linking the environment with cancer risk. BMJ. 2000;321:847–8.

    PubMed Central  CAS  PubMed  Google Scholar 

  30. Cowey S, Hardy RW. The metabolic syndrome: a high-risk state for cancer? Am J Pathol. 2006;169:1505–22.

    PubMed Central  CAS  PubMed  Google Scholar 

  31. van Kruijsdijk RC, van der Wall E, Visseren FL. Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomarkers Prev. 2009;18:2569–78.

    PubMed  Google Scholar 

  32. Shin E, do Park J, Kim HH, Won NH, Choe G, Lee HS. Adiponectin receptor expression in gastric carcinoma: implications in tumor development and progression. J Cancer Res Clin. 2013;139:709–18.

    CAS  Google Scholar 

  33. Olefsky JM, Glass CK. Macrophages, inflammation, and insulin resistance. Annu Rev Physiol. 2010;72:219–46.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to An-Kui Yang.

Additional information

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

LZ developed the algorithm. A-KY, T-RL, and LZ carried out most of the analyses. A-KY, T-RL, and LZ participated in the design of the study and helped algorithm development. T-RL and LZ drafted the manuscript. A-KY conceived and coordinated the study. All authors have read and approved the final manuscript.

Lan Zou and Tian-Run Liu contributed equally to this work.

Rights and permissions

Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit

The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zou, L., Liu, TR. & Yang, AK. Metabolic syndrome is associated with better prognosis in patients with tongue squamous cell carcinoma. Chin J Cancer 34, 9 (2015).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: