Comprehensive analysis of the differences between left- and right-side colorectal cancer and respective prognostic prediction.

Background: Previous studies have reported that the tumor heterogeneity and complex oncogenic mechanisms of proximal and distal colon cancer (CRC) are divergent. Therefore, we aim to analyze the differences between left-sided CRC (L_cancer) and right-sided CRC (R_cancer), as well as constructing respective nomograms.

Methods: We enrolled 335 colon cancer patients (146 L_cancer patients and 189 R_cancer patients) from The Cancer Genome Atlas (TCGA) data sets, and 102 pairs of color cancer tissue and adjacent normal tissue (51 L_cancer patients and 51 R_cancer patients) from our hospital. Firstly, we analyzed the differences between the L_cancer patients and R_cancer patients, and then established the L_cancer and R_cancer prognostic models using LASSO Cox.

Results: R_cancer patients had lower survival than L_cancer patients. R_cancer patients had higher ESTIMATE and immune scores and lower tumor purity. These patterns of expression of immune checkpoint-related genes and TMB level were higher in R_cancer than in L_cancer patients. Finally, we using Lasso Cox regression analyses established a prognostic model for L_cancer patients and a prognostic model for R_cancer patients. The AUC values of the risk score for OS in L_cancer were 0.862 in the training set and 0.914 in the testing set, while those in R_cancer were 0.835 in the training set and 0.857 in the testing set. The AUC values in fivefold cross-validation were between 0.727 and 0.978, proving that the two prognostic models have great stability. The nomogram of L_cancer included prognostic genes, age, pathological M, pathological stage, and gender, the AUC values of which were 0.800 in the training set and 0.905 in the testing set. Meanwhile, the nomogram of R_cancer comprised prognostic genes, pathological N, pathological T, and age, the AUC values of which were 0.836 in the training set and 0.850 in the testing set. In the R_cancer patients, high-risk patients had a lower proportion of 'B cells memory', 'Dendritic cells resting', immune score, ESTIMATE score, immune checkpoint-related genes, and HLA-family genes, and a higher proportion of 'T cells follicular helper', 'Dendritic cells activated', and 'Mast cells activated'.

Conclusions: We found significant differences between L_cancer and R_cancer patients and established a clinical predictive nomogram for L_cancer patients and a nomogram for R_cancer patients. Additionally, R_cancer patients in low-risk groups may be more beneficial from immunotherapy.