Paper: Higher platelet-to-lymphocyte ratio is prevalent in the presence of circulating tumor microemboli and is a potential prognostic factor for non-metastatic colon cancer.

Translational Oncology 14 (2021) 100932
https://doi.org/10.1016/j.tranon.2020.100932

Background and present state of implementation

Colorectal cancer is the third most commonly diagnosed cancer worldwide. In 2020, colon cancer accounted for 104,610 cases diagnosed in both genders in United States (Siegel, Miller & Jemal, 2020). The only curative treatment for localized disease is surgical resection. The 5-year survival rates for patients with stage I–III colon cancer range are high (71–90%), however, some patients experience local or distant recurrences (ACS, 2020). So, there is a need for biomarkers that can be used to identify which patients with non-metastatic tumors are likely to be responsive or resistant to therapies.

We have been working with CTCs (Circulating tumor cells; cells that leave primary tumor and invade the blood sytem early in the metastatic process) in metastatic colon disease for a long time and were able to show that CTCs counts and kinetics are prognostic factors in this scenario (OncoTargets and Therapy 2016:9 7503–7513; Diagnostics 2021, 11, 502). In the case of patients treated with target therapies, when primary tumor is not available for KRAS analysis, we showed that CTCs can be used as surrogates (Cancer Biology & Therapy 16:9, 1289-1295; 2015). In metastatic disease we also showed that protein analysis of genes related to resistance to chemotherapy (tymidilate synthase and multidrug resistance therapy-1) can be evaluated in CTCs and that their expression in these cells directly correlated with disease progression. Their expression in primary tumor and metastasis did not correlate with disease progression (Int. J. Cancer: 137, 1397–1405; 2015; Int. J. Cancer: 139, 890–898; 2016).

In the paper applied for the ICPerMed Recognition (Translational Oncology 14 (2021), we decided to work with early stage colon disease and showed that stages I-III release CTCs (median number of 69 patients=2.5 CTCs/mL), which was surprising, and that the levels were related to tobacco use. The circulating tumor microemboli (CTM, CTCs in clusters of three or more cells) presence was related to platelet-lymphocyte ratio (PLR). Patients with a high PLR (> 124) were mostly (75.6%) diagnosed with high-risk stages II/III cancer (stages I/low-risk II, 24.4%; p = 0.014). All 8 patients that had disease recurrence during follow-up had a high PLR (p = 0.02). The findings of this paper show that not only CTCs and CTM, but also PLR (an easy and old tool obtained by blood count analysis) may be clinically relevant for management and risk stratification of patients with early stage diseases, that is when any therapeutic or diagnostic intervention can be really useful to help patients and avoid tumor evolution.

We believe that our study can be useful for personalized medicne application, as we propose tools (CTCs, CTM and PLR) that can be individually evaluated along the disease time course, indicating for the clinican when to interview in each patient.

Contact information:

Ludmilla Thomé Domingos Chinen
Coordinator of Translational Medicine Laboratory of Núcleo de Ensino e Pesquisa da Rede São Camilo São Paulo, Brazil
Address: Av. Conselheiro Rodrigues Alves, 820 Vila Mariana, São Paulo, Brazil CEP: 04014-002
e-mail:  ltdchinen@gmail.com / ludmilla.chinen@hospitalsaocamilosp.org.br