Baumgartner et al. first proposed the concept of "sarcopenia" [22] to describe the decrease in muscle mass of the elderly with age in 1998. The occurrence of sarcopenia is closely related to age and special physiological conditions which has received extensive attention from scientists in recent years. Many studies have shown that sarcopenia is associated with an increased risk of recurrence [23], shortened survival time [24–25] and increased other causes of death [26] after gastric cancer resection.Weight loss and malnutrition are issues that are very worthy of our attention in all stages of gastric cancer treatment. More than half of patients with gastric cancer have some degree of weight loss due to the potential impact of the tumor at the time of diagnosis [27]. The inability to maintain weight is considered to be a poor prognostic factor that affects long-term survival during neoadjuvant therapy or chemotherapy [28–29].
The relationship between Cr/CysC ratio and sarcopenia in different populations has been discussed. Tetsuka et al. found for the first time that the Cr/CysC ratio of patients with amyotrophic lateral sclerosis was lower than that of healthy people [30]. In the Japanese elderly without severe renal impairment, the Cr/CysC ratio is positively correlated with muscle mass and physical function [31].The reduction of Cr/CysC ratio is considered to be a predictor of sarcopenia in patients with type 2 diabetes and COPD[32–33]. Recent studies have found that the Cr/CysC ratio can also predict malnutrition, weakness and poor clinical outcomes in ICU patients [34–36]. However, there is no report confirming the association between Cr/CysC ratio and sarcopenia in patients with gastric cancer.
This study shows that the serum Cr/CysC ratio is a useful predictor of sarcopenia compared with other biomarkers (such as serum Cr, CysC). In addition, the best cut-off value of serum Cr/CysC ratio is 0.67.Patients with Cr/CysC ≥ 0.67 can basically rule out sarcopenia.
We found that the Cr/CysC ratio is the most predictive of sarcopenia in patients with gastric cancer which is positively correlated with SMI and SMA among the three biomarkers of serum Cr, serum CysC and serum Cr/CysC ratio in this study. Previous studies have shown that serum Cr is related to muscle mass [37–38]. In our study, serum Cr is positively correlated with SMI and SMA which is consistent with the results of previous studies.Serum CysC does not show any correlation with muscle mass. As an indicator of renal function, serum CysC has received more and more attention in recent years. It is a low molecular weight protein with a stable production rate and can be freely filtered by the glomerulus [39]. Therefore, the Cr/CysC ratio obtained by calibrating Cr with CysC, that is not affected by muscle mass, can predict sarcopenia.
We found that the best cut-off value of the optimal serum Cr/CysC ratio for predicting sarcopenia in patients with gastric cancer is 0.67. A study found that the optimal cut-off value of Cr/CysC ratio in diabetic patients for predicting sarcopenia was 0.9 [32], while another study found that the optimal cut-off value of Cr/CysC ratio was 0.71 in COPD patients[33]. However, there is no study to detect the optimal cut-off value of Cr/CysC ratio for sarcopenia in gastric cancer patients as we know.
The OS of the high serum Cr/CysC group defined by the optimal cut-off value was significantly higher than that of the low serum Cr/CysC group.And sarcopenia shorted the survival time of patients as an independent factor affecting the prognosis of gastric cancer patients which result is consistent with that of Cr/CysC ratio. We also constructed height-calibrated Cr/CysC ratio and SMI and survival models. Studies have shown that although the Cr/CysC ratio is related to OS, the correlation is not as good as SMI. But its correlation is greater than SMI when it is used together with SMI as an indicator to measure the prognosis of patients with gastric cancer.This means that the prognosis of gastric cancer patients can be predicted by using the Cr/CysC ratio and SMI as a combined index.
In this study, we used the area of all skeletal muscle on the CT scan at the L3 level as the standard for estimating the patient's skeletal muscle mass. Many studies have confirmed that CT scans are an effective way to assess body composition and can predict sarcopenia in the population.It has been widely used in oncology as a highly feasible method. However, it is still subject to many limitations in actual clinical applications as a method of evaluating body composition, such as its high radioactivity and high cost. In addition, the measurement of grip strength and pace is often used to assess sarcopenia.But this method is very dependent on patient compliance and is often difficult to implement in clinical operations. However, early diagnosis and intervention are very important since sarcopenia can significantly affect the prognosis of patients with gastric cancer. Serum Cr/CysC ratio is a simple, easy and low-cost method that can initially screen patients for sarcopenia and assist subsequent treatment and intervention. If the Cr/CysC ratio is lower than 0.67, detailed examinations must be carried out by BIA, DEXA, CT or MRI.
This study also has certain limitations. First of all, it is a retrospective study and sometimes there are certain deficiencies when collecting follow-up information. Second,the sample size is insufficient because this study only included data from a tertiary center for statistical analysis. The detection of serum Cr and serum CysC will also be affected by reagents and instruments. In follow-up studies, prospective studies can be carried out around this point of view and verified in other centers. Third, this study only referred to the Chinese population. Due to the different criteria for sarcopenia, this limits the applicability of the conclusions, especially for Western populations. In follow-up research, how to determine the appropriate standards according to different groups of people to verify our conclusions is very important.