Is sarcosine a biomarker for prostate cancer?

Background

As a male-specific malignant tumor, the incidence of prostate cancer is gradually increasing. Its pathogenesis may be related to age, race, genetics, lifestyle, hormones and other factors. Previous studies have suggested that there are three main risk factors associated with prostate cancer, namely age, race and genetics Due to the long incubation period of prostate cancer, it is generally not easy to detect in the process of occurrence and development. Prostate cancer is found in 80 % of patients in China until distant metastasis occurs, thus missing the best treatment opportunity and poor prognosis [1]. Therefore, whether from the perspective of solving the problem of clinical diagnosis and treatment of prostate cancer, or from the perspective of improving the survival rate of cancer patients and reducing the cost of treatment, it is urgent to find biomarkers with higher specificity, especially those that can characterize the invasiveness of prostate cancer.

Research has shown that sarcosine levels are significantly elevated in patients with invasive prostate cancer. By collecting urine samples from these prostate cancer patients, sarcosine can be easily detected, making clinical testing sampling relatively easy. Further research has confirmed that when sarcosine is added to benign prostatic epithelial cells, the cells exhibit aggressive behavior, while reducing sarcosine levels in cancer cells can alleviate aggressive behavior [2]. These studies suggest that  sarcosine has great potential as a biomarker for characterizing the invasiveness and progression of prostate cancer[3].

With the increasing research on sarcosine, some results support sarcosine as a diagnostic biomarker for prostate cancer and have the potential to replace PSA; The other part holds a negative attitude [4-6]. Researchers suspect that the reason for these two views may be related to the detection method of sarcosine [5]. They inferred that there are many forms of alanine in the human body, which are very similar to sarcosine. However, the gas chromatography-mass spectrometry method used cannot effectively separate sarcosine and alanine, and cannot avoid the interference problem of alanine. Therefore, the conclusions of this study cannot guarantee their correctness.

If sarcosine can become an effective biomarker for the diagnosis of prostate cancer, once put into clinical application, it can not only greatly improve the accuracy and convenience of clinical diagnosis of prostate cancer, but also bring good news to patients, and the social and economic benefits will be considerable.

Research summary[7]

Objective: To establish a method for the determination of urinary sarcosine in Chinese healthy population by using liquid chromatography-tandem mass spectrometry (LC-MS/MS).Prostate cancer, and verify the feasibility of sarcosine as a biomarker for the diagnosis of prostate cancer.

Methods 

This study established a method for the determination of sarcosine (creatinine) and creatinine concentration in human urine by liquid chromatography-tandem mass spectrometry. The method was applied to detect sarcosine and creatinine, and had good specificity, accuracy,precision and sensitivity.329 cases of male patients who were not admitted to the prostate cancer and 167 patients with prostate cancer were enrolled in the Department of Urology, Xuhui District Central Hospital, Shanghai.

Results

The sarcosine detection method established in this study can effectively avoid the interference of alanine on sarcosine. High performance liquid chromatography uses post-column derivatization to quantitatively detect amino acids. Combined with stable isotope-labeled liquid chromatography tandem mass spectrometry, the content of sarcosine can be accurately quantified. The results obtained by this method are consistent with the results of Sreekumar et al.[2], indicating that sarcosine has the potential to be a diagnostic marker for prostate cancer.The accuracy, specificity, residual, extraction recovery, medium effect and stability of the analytical method were in accordance with the requirements. The levels of urinary sarcosine (mg/g creatinine) in the healthy population were (0.115±0.077) mg/g creatinine in the healthy population and 167 patients with prostate cancer were (0.797±0.909) mg/g creatinine, the median of 0.426mg/g creatinine. The median urinary creatinine (mg/g creatinine) level was (0.797±0.909) mg/g creatinine in patients with prostate cancer. The box distribution of urinary sarcosine in healthy people and prostate cancer patients is shown in Fig.1. It can be seen that the fluctuation of urinary sarcosine level in prostate cancer is greater than that in healthy people. Non-parametric K-S analysis showed that urinary sarcosine levels were skewed in both healthy and prostate cancer populations. The square distribution of urinary sarcosine in healthy people and prostate cancer patients is shown in Fig.2.

Conclusion

Urinary sarcosine levels in patients with prostate cancer were significantly higher than those in healthy subjects (p<0.001, t-test). The normal reference range for urinary sarcosine was set to <0.264 mg/g creatinine. Considering that the degree of urinary sarcosine in patients with prostate cancer is relatively large, a more stringent 99% percentile of urinary sarcosine, or 0.356 mg/g creatinine, is recommended for clinical diagnosis as a diagnostic threshold for prostate cancer. The area under the ROC curve of urinary sarcosine was 0.898 (95%CI 0.866-0.930, p<0.001). It was found that urinary sarcosine had a high diagnostic value for prostate cancer. Compared with localized prostate cancer, urinary sarcosine levels in metastatic prostate cancer were significantly higher (p<0.001). In the high degree of malignancy, urinary creatinine levels in the death cases were significantly increased. Urinary sarcosine levels are important for distinguishing prostate cancer malignancy, metastatic, and predictable clinical survival, and can characterize the invasive and progression of prostate cancer, noninvasive biomarkers.

References

[1]Ye DW, Epidemiology of prostate cancer and incidence trends in China. Chinese Journal of Surgery, 2006,44(6):362-364.

[2]Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature, 2009, 457(7231):910-914.

[3]Cernei N, Heger Z, Gumulec J, et al. Sarcosine as a potential prostate cancer biomarker--a review. Int J Mol Sci. 2013;14(7):13893-13908.

[4]Giuseppe Lucarelli, et al. Serum sarcosine increases the accuracy of prostate cancer detection in patients with total serum PSA less than 4.0 ng/ml. Prostate, 2012,72:1611-1621. 

[5]Issaq HJ, Veenstra TD. Is sarcosine a biomarker for prostate cancer? J.Sep.Sci, 2011,34:3619-3621. 

[6]Jentzmik F, Stephan C, et al. Sarcosine in prostate cancer tissue is not a differential metabolite for prostate cancer aggressiveness and biochemical progression.J Urol, 2011,185:706-711.

[7]Chen M. Exploration of new markers and diagnostic threshold range of sarcosine-prostate cancer [D].Shanghai University.2017,5:1-50.

You may like