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.