Baumgartner et al. first proposed the concept of "sarcopenia"  in 1998 to describe muscle mass decrease in older patients, as they age. Sarcopenia is closely related to age and specific physiological conditions, and has recently received extensive attention. Several studies have shown that sarcopenia is associated with an increased risk of recurrence , shortened survival time [24–25], and increased other causes of death  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 owing to the impact of the tumor at the time of diagnosis . Furthermore, an inability to maintain weight is considered 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. reported that the Cr/CysC ratio of patients with amyotrophic lateral sclerosis was lower than that of healthy people . In Japanese older people without severe renal impairment, Cr/CysC ratio is positively correlated with muscle mass and physical function . Low Cr/CysC ratio is considered a predictor of sarcopenia in patients with type 2 diabetes and chronic obstructive pulmonary disease (COPD) [32–33]. Recent studies showed that Cr/CysC ratio can also predict malnutrition, weakness, and poor clinical outcomes in intensive care unit patients [34–36]. However, to our knowledge, no reports have confirmed an association between Cr/CysC ratio and sarcopenia in patients with gastric cancer.
This study showed that serum Cr/CysC ratio is a useful predictor of sarcopenia compared with other biomarkers, such as serum Cr and CysC, individually. In addition, the best cut-off value for serum Cr/CysC ratio was 0.67, and in patients with a Cr/CysC ratio ≥ 0.67, sarcopenia can essentially be ruled out.
We found that the Cr/CysC ratio is the most predictive of sarcopenia in patients with gastric cancer, and that the ratio was positively correlated with SMI and SMA among the three biomarkers, serum Cr, serum CysC, and serum Cr/CysC ratio. Previous studies have shown that serum Cr is related to muscle mass [37–38]. In our study, serum Cr was positively correlated with SMI and SMA, consistent with findings in previous studies. Serum CysC showed no correlation with muscle mass. As an indicator of renal function, serum CysC has recently received greater attention. Serum CysC is a low-molecular-weight protein with a stable production rate and it can be freely filtered by glomeruli . Therefore, Cr/CysC ratio is not affected by muscle mass and can predict sarcopenia.
We found that the best cut-off value for the optimal serum Cr/CysC ratio for predicting sarcopenia in patients with gastric cancer is 0.67. A previous study found that the optimal cut-off value for Cr/CysC ratio in diabetic patients for predicting sarcopenia was 0.9 , while another study found that the optimal cut-off value was 0.71 in COPD patients . However, to our knowledge, no studies have determined the optimal cut-off value for sarcopenia in gastric cancer patients.
The OS of the high serum Cr/CysC group defined by the optimal cut-off value was significantly longer than that of the low serum Cr/CysC group. Sarcopenia shortened gastric cancer patients’ OS as an independent factor affecting the prognosis. And the results of both are consistent. We also determined the height-calibrated Cr/CysC ratio and SMI, and created survival models. Studies have shown that although Cr/CysC ratio is related to OS, the correlation is not as good as with SMI. However, the ratio’s correlation is greater than that for SMI when the ratio is used with SMI as an indicator of prognosis in patients with gastric cancer. This means that the prognosis of gastric cancer patients can be predicted using the Cr/CysC ratio and SMI as a combined index.
In this study, we used the area of all skeletal muscle on CT images at the L3 level as the standard for estimating a patient's skeletal muscle mass. Several studies have confirmed that CT is effective for assessing body composition, and that CT can predict sarcopenia in the general population. CT is widely used in oncology as a highly feasible method; however, CT is limited clinically as a method of evaluating body composition because of the high radiation level and cost. As an alternative, measuring 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 clinically. However, early diagnosis and intervention for sarcopenia are very important because 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 be used to screen patients for sarcopenia and assist in determining subsequent treatment and intervention. If the Cr/CysC ratio is < 0.67, detailed examinations must be performed, such as bioelectrical impedance analysis, dual energy X-ray absorptiometry, CT, or magnetic resonance imaging.
This study has certain limitations. First, this was a retrospective study, and there were deficiencies when collecting the patients’ follow-up information. Second, the sample size was insufficient because we included data only from a tertiary center, for the statistical analysis. Additionally, serum Cr and serum CysC measurements are affected by reagents and instruments. Future prospective studies in multiple centers are needed to address these issues. Third, this study involved only the Chinese population, and different criteria for sarcopenia limit the applicability of our conclusions, especially for Western populations. Studies determining appropriate standards for determining sarcopenia according to different populations are very important.