To our knowledge, this is the first study to evaluate the predictive ability of preoperative factors for sarcopenia in patients with colorectal cancer. We established a predictive model to predict the condition of sarcopenia. In our study, smoking history, drinking history, diabetes, TNM stage, nutritional status and physical activity were independent risk factors for sarcopenia in the training cohort. Then we used these six prediction factors to develop a prediction model, which was presented in the form of nomogram, which was easy to observe and use. Nomogram had good prediction ability, and the AUC values in training queue and verification queue are 0.971(95%CI:0.954-0.988) and 0.922(95%CI:0.820-1.000) respectively. Nomogram's calibration curve showed a good correction effect in both the training queue and the verification queue. Our results showed that easily available preoperative factors can effectively predict sarcopenia, which was beneficial to the early intervention and treatment of these patients.
Smoking and drinking were independent risk factors for sarcopenia in patients with colorectal cancer. Locquet M etal[11] conducted a longitudinal study to investigate the relationship between smoking and sarcopenia, the results showed that smokers had a 2.68 times higher risk of developing sarcopenia than non-smokers, and sensitivity analysis confirmed these findings globally. There were some volatile and soluble components in tobacco, including ROS, aldehyde, and reactive nitrogen species (RNS), these ingredients can enter the smoker's blood and reach the skeletal muscle. In skeletal muscle, the components of tobacco directly or indirectly increase oxidative stress, lead to p38MAPK phosphorylation, further activate nuclear factor-kB (NF-kB) pathway, and degrade IkB protein, resulting in nuclear translocation of nuclear factor-kB. The upregulation of these ligases can increase the protein degradation of skeletal muscle, thus accelerating the progression of sarcopenia[12]. Similar to smoking, excessive drinking was associated with impaired protein metabolism in skeletal muscle. The increase of alcohol intake may lead to urinary incontinence and hepatocyte damage, stimulate the body to produce high concentrations of ammonia[13,14], lead to hyperammonemia, and thus disrupt the balance of skeletal muscle protein metabolism[15]. In addition, if patients had both excessive drinking and smoking, the inhibitory effect of systemic inflammation on the incidence of muscle protein synthesis (MPS) was additive. It will change the oral flora of acetaldehyde, which may increase autophagy and hyperammonemia, as well as the expression of muscle inhibin, MAFbx and the down-regulation mechanism of MPS, thus leading to the occurrence of sarcopenia[14].
The relationship between diabetes and sarcopenia has been confirmed. A study based on DXA measurements of skeletal muscle index showed that 15.7% of patients with type 2 diabetes developed sarcopenia, compared with 6.9% in the general population[16] .In our study, 43.66% of diabetic patients developed sarcopenia. insulin resistance generally occurs in diabetic patients, thus breaking the balance of muscle protein synthesis and degradation, resulting in a decrease in muscle content. if the supply of glucose remains unchanged, it will in turn reduce insulin sensitivity, leading to a vicious circle[17]. In addition, insulin resistance can also cause disorders in calcium uptake and affect muscle contraction, which further increases the risk of sarcopenia[18].
This study showed that there was a correlation between TNM stage and sarcopenia. in our study, patients with III/IV stage were 5.1 times more likely to develop sarcopenia than patients with I/II stage. Patients with stage III/IV of colorectal cancer are more prone to negative nitrogen balance and negative energy balance caused by loss of appetite and abnormally high metabolism because the cancer cells have spread to the surrounding lymph nodes and distant tissues[19]. In order to meet the energy needs of the body, the oxidation of non-essential amino acids in skeletal muscle increases, which accelerates the degradation of protein in skeletal muscle and eventually leads to sarcopenia[20]. However, the study conducted by Souza showed that there was no difference in the duration of the tumor[8].
Most studies investigated the relationship between nutritional status and muscular dystrophy. Patients with colorectal cancer, as a common digestive tract tumor, are prone to malnutrition, which may be due to reduced intake, impaired digestive function, poor absorption of nutrients and so on[21] .A study of elderly hospitalized patients in acute post-care reported that 15% of patients coexisted with malnutrition and sarcopenia[22], which was similar to our findings. In a recent systematic review, 23% of hospitalized elderly patients coexisted with malnutrition and sarcopenia[23] .Beaudart et al[24] followed up the malnourished elderly in the community for four years and found that the risk of developing sarcopenia / severe sarcopenia (EWGSOP2) tripled during the follow-up period. The link between malnutrition and severe sarcopenia can be explained by low intake of nutrients such as vitamin D, protein and calcium, which affects muscle mass preservation, which in turn affects muscle strength and physical fitness[25]. However, we also need to assess the causal relationship between malnutrition and sarcopenia, which requires longitudinal data on nutritional status and dietary intake for further study. Physical activity is considered to be the main factor in stimulating muscle protein synthesis, has a protective effect on sarcopenia, and can reduce the probability of developing sarcopenia[26] ,which is similar to the results of this study. 69.64% of patients with moderate and low exercise ability in our study developed sarcopenia, while only 1.54% of patients with high exercise ability developed sarcopenia. A great deal of evidence has proved that effective exercise intervention can prevent the occurrence and development of sarcopenia[27]. Exercise intervention includes aerobic and resistance exercise, both of which can increase the muscle mass of the human body in varying degrees. Especially high-intensity resistance exercise can effectively improve or prevent the decrease of muscle fibers and increase muscle strength[28] .Some studies have found that the combination of nutrition and exercise intervention plays an important role in the prevention and treatment of sarcopenia, which can improve the muscle strength of patients more than exercise intervention or nutrition intervention alone[29].
Therefore, patients with history of smoking, drinking, diabetes, high tumor stage, malnutrition and low exercise ability should be given corresponding nutrition and exercise intervention according to the actual situation of the patients. Studies have confirmed that appropriate nutrition and exercise intervention can effectively delay the occurrence and development of sarcopenia.
There are still some limitations in this study. First of all, this was a single-center study with a small sample size. the sample size of the research data should be increased in the later stage, and the results should be verified in the multicenter study in order to obtain a more accurate and stable risk prediction model for sarcopenia. Second, the average BMI in our study was relatively low, which may be more representative of the Asian population. Further research was needed to verify the performance of our nomogram in obese people. To sum up, we had developed a new predictive model to predict the risk of sarcopenia in patients with colorectal cancer. The model suggested that smoking, drinking, diabetes, tumor stage, nutritional status and exercise ability may be the risk factors of sarcopenia. Medical staff should identify the risk of sarcopenia early and give targeted intervention measures to improve the quality of life of patients with colorectal cancer.