Abstract
BackgroundClinical and molecular characteristics differ between right-sided and left-sided colorectal cancer (CRC). This study aimed to clarify the correlation between CRC sidedness and tumor immunity.MethodsA total of 102 patients who underwent curative colectomy for stage II/III CRC were included in this study. The expression of programmed cell death (PD)-1, PD1-ligand 1 (PD-L1), forkhead box P3 (Foxp3), transforming growth factor (TGF)-β, and indoleamine-pyrrole 2,3-dioxygenase (IDO) were examined using immunohistochemistry and the relationships between sidedness and several prognostic factors were examined.ResultsClinicopathological factors were not significantly different between right- and left-sided CRC. The tumor immunity-related molecule PD-L1 was more highly expressed in right-sided than in left-sided CRC (62.9% vs. 30.6%, p<0.01). No significant difference was found in overall survival (OS) and disease-free survival (DFS) by sidedness. PD-1 and Foxp3 expression were significant prognostic factors for OS. Lymph node metastasis (N), lymphatic invasion (ly), and PD-L1 expression were significant prognostic factors for DFS. In right-sided CRC, IDO-positive patients had a poor OS (p<0.05), and IDO was the only independent prognostic indicator for OS. N and venous invasion were identified as independent prognostic indicators for DFS. In left-sided CRC, univariate analysis identified PD-1, PD-L1, and Foxp3 expression as significant predictors of poor OS. Multivariate analysis confirmed PD-L1 expression as an independent prognostic indicator. N, ly, and PD-L1 expression levels were identified as significant predictors of poor DFS.ConclusionsThe prognostic factors were IDO in right-sided CRC and PD-L1 and Foxp3 in left-sided CRC. These findings indicated that tumor immunity might play different roles depending upon sidedness. Tumor location may be an important factor to consider when assessing immune response and therapeutic decisions in CRC patients.
Highlights
Colorectal cancer (CRC) is one of the most common cancers in both men and women worldwide
The tumor immunity-related molecule programmed cell death (PD)-L1 was more highly expressed in rightsided than in left-sided colorectal cancer (CRC) (62.9% vs. 30.6%, p
No significant difference was found in overall survival (OS) and disease-free survival (DFS) by sidedness
Summary
Colorectal cancer (CRC) is one of the most common cancers in both men and women worldwide. Accumulating evidence indicates that CRC shows differences in pathogenesis, molecular pathways, and prognosis depending on the sidedness [1]. Kirsten rat sarcoma viral oncogene homolog (KRAS) and p53 mutations have been characterized as left-sided CRC [2]. Microsatellite instability (MSI)-high, B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutation, and CpG island methylator phenotype (CIMP)-high are often characterized as right-sided CRC [1, 3]. The aim of this study was to reveal the correlation of CRC sidedness with tumor immunity. Clinical and molecular characteristics differ between right-sided and left-sided colorectal cancer (CRC). This study aimed to clarify the correlation between CRC sidedness and tumor immunity
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