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Comparison of urine proteomes from tumor-bearing mice with those from tumor-resected mice

Heng Ziqi et al have developed a diagnostic tool using urine biomarker analysis for post tumor resection. The disappearance of protein biomarkers after resection helps in determining the success of the surgical procedure. For the purpose of the study, 10 mice were injected with the MC38 cell line into the right hind limb, and 5 mice served as healthy controls. They had similar surgical procedures to ensure that the changes due to wound healing do not overlap with the tumor resection process. There are some points that I would like to highlight in the study.

Major Issues regarding the study:

1. For chronic conditions (like cancer), the serum biomarker will not diminish immediately after treatment/surgery. If we consider appropriate time points, we can highlight different aspects of the pathophysiology condition of the subject. Hence we cannot discount the importance of blood biomarker discovery.

2. In order to test the reproducibility of the study, the consistency of biomarkers among different cell lines should be tested.

3. In order to eliminate the chances of false association of suggested biomarkers with the changes post-resection, multiple time points are required. If the changes in the tumor microenvironment hamper the wound healing response compared to healthy wildtype, then there is a chance that the biomarkers reported could be due to slow healing of the tissue.

4. If there would have been partial resection of the tumor, then we might get a few more biomarkers as the effect of tumor regrowth and the metastasis response by the body would have been more realistic scenario.

5. The changes in the urine proteome depend on various factors. If it is considered urine as a sink for waste disposal in case of chronic conditions, then the changes could be rapid. In such cases, the proteome should be monitored continuously to validate if the changes are really due to treatment or amelioration of the chronic condition.

6. The process of change in the urine proteome biomarker could be further elucidated from the data. Linking the results with the processes involved in the tissue damage repair mechanism and withdrawal of immune response can provide insight into the difference between complete resection and the condition between primary tumor disappearance and secondary tumor appearance.

Minor issues which could have been addressed in this article:

1. The cancer progression in different tissue should be considered while developing this diagnostic tool.

2. If the changes in the serum biomarker would have been considered, then this would have been a more comprehensive study.

3. In human cancer patients, the changes in urine biomarkers are largely affected by ongoing therapy, diet, and multiple surgical procedures. In that case, how does the author suggest that we should plan out urine collection?

4. With the MC38 cell lines the author has established the time period for this study. This ensures that the biomarker clears out in case of complete resection. But this does not consider the cases where cancer cell dormancy occurs.

Competing interests

The author declares that they have no competing interests.