Abstract
Simple SummaryColorectal cancer (CRC) is one of the most common cancers worldwide. Novel markers have been investigated in order to better predict the course of disease and adjust the treatment. Markers associated with cancer-related inflammation (CRI), both in the bloodstream and the tumor tissue, have been in the spotlight for years. In this study, we investigate whether blood-based markers: lymphocyte-to-monocyte ratio, neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio, correlate with tissue-based markers, such as tumor-infiltrating lymphocytes. We retrospectively analyzed 87 patients with locally advanced left-sided CRC treated with radical surgery. Fifty patients were found suitable for the study. We compared the results of their blood tests from the time of the surgical intervention and the density of lymphocytes in the resected tumors. We found no correlation between local and peripheral markers of CRI. Further prospective studies are needed to confirm the results.Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Novel markers are required in order to select high-risk patients and better adjust the treatment. Both peripheral and local markers of cancer-related inflammation (CRI) such as lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR) and tumor-infiltrating lymphocytes (TILs) have been thoroughly investigated in recent years and deemed to be highly prognostic. We hypothesized that there is an association between local and peripheral CRI indices and that blood-based biomarkers may serve as a surrogate of TILs. We retrospectively analyzed 87 patients with locally advanced left-sided CRC treated with radical-intent surgery in the Maria Skłodowska-Curie National Research Institute of Oncology in Warsaw, Poland, between January 2014 and December 2015. Fifty patients were found eligible for the study. The patients were divided in terms of pre-treatment values of systemic inflammatory response (SIR) markers into LMR/NLR/PLR-high and low groups. We evaluated the resected specimens by immunohistochemistry in order to assess the densities of CD3+ and CD8+ lymphocytes in the center of the tumor and in the invasive margin. We found that the level of CD3+ lymphocytes in the center of the tumor was statistically significantly higher in patients with low pre-treatment NLR (p = 0.044); however, no correlation between any of the SIR markers and CD3+ or CD8+ TILs was observed. Five-year overall survival (OS) was longer in patients with high LMR (p < 0.001), low NLR (p = 0.001) and low PLR (p = 0.095). No correlation between the density of TILs and OS was demonstrated. In conclusion, based on our study, peripheral blood-based markers and CD3+ and CD8+ TILs are not interrelated.
Highlights
Colorectal cancer is the third most common cancer and the second most common cause of cancer-related death worldwide [1]
The “Immunoscore”—a value based on the density of CD3+ and CD8+ tumor-infiltrating lymphocytes (TILs) in the tumor center (CT) and the invasive margin (IM)—has been shown to be highly prognostic in colon cancer
We found no correlation between pre-treatment lymphocyte-tomonocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and the density of CD3+ and CD8+ TILs, Table 4
Summary
Colorectal cancer is the third most common cancer and the second most common cause of cancer-related death worldwide [1]. The Union for International Cancer Control (UICC) tumor node metastasis (TNM) staging system is the most reliable indicator of patient prognosis and is widely used among practitioners to determine the most appropriate therapy [3]. Cancer-related inflammation (CRI) indices, both in the peripheral blood and in the tumor microenvironment, may be suitable for this role. Peripheral systemic inflammatory response (SIR) markers such as LMR, NLR or PLR have potent prognostic value in many malignancies [4–6]. The “Immunoscore”—a value based on the density of CD3+ and CD8+ TILs in the tumor center (CT) and the invasive margin (IM)—has been shown to be highly prognostic in colon cancer. Some reports have suggested the superior role of the Immunoscore in predicting survival compared to the TNM staging system [7]. We tried to evaluate the correlation between local (TILs) and peripheral (LMR, NLR and PLR) CRI biomarkers in CRC patients
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