There is growing evidence indicating that, beyond the TNM stage, factors such as nutrition and inflammation play crucial roles in predicting the survival of patients with CRC (9, 10). We created and verified a classification system that incorporates data on cancer genes, supplementing information from nutritional and inflammatory factors. Our developed classification methods have shown strong performance in predicting postoperative outcomes for CRC patients. These user-friendly models are valuable for guiding treatment decisions and follow-up strategies for individuals with CRC.
We used serum albumin, lymphocyte counts, and RAS mutations as prognostic factors in this study. Hypoalbuminemia serves as an indicative marker for malnutrition and cachexia, with some studies demonstrating its correlation with adverse outcomes across diverse cancer types (11, 13). Lymphocytes play a crucial role in the host's immune function, and a reduction in their numbers corresponds to a decline in the host's antitumor immunity, resulting in a poorer prognosis (14, 15). The prognosis prediction using lymphocytes includes the NLR and LMR. It has been reported that each of these is an independent prognostic factor in patients with CRC (6, 7). Upon scrutinizing RAS mutants, it was observed that the G12V variant exhibited a diminished GTPase activity, amounting to 25% of the G12D mutant and a mere 10% of the wild-type form (16, 17). Additionally, these RAS mutations exhibited a decreased affinity for binding GTPase-activating proteins, further compromising GTPase function. This alteration in functionality modifies the threshold required for triggering cancer apoptosis, potentially amplifying the transformative capabilities of cells and evading apoptosis (18, 19). Consequently, colorectal cancer harboring G12V or G12C mutations has been associated with an unfavorable prognosis (4, 20).
Within the High-ALRI group, a higher incidence of right-sided colorectal cancer cases was observed, along with a greater representation of elderly patients. This observation aligns with a reported trend wherein a comparison of clinicopathological characteristics between right-sided and left-sided colorectal cancers revealed a higher prevalence of elderly patients on the right side of the colon (21). The High-ALRI group exhibited a higher incidence of lymphatic invasion and elevated levels of tumor markers, indicating a greater number of positive cases. This observation suggests that a significant portion of the patients in this group may be experiencing advanced stages of cancer. Further, ALRI demonstrated utility in Stage II and Stage III CRC patients, implying that in Stage I colorectal cancer, alterations in albumin and lymphocyte levels might be less pronounced, potentially due to the smaller tumor volume (11).
In comparison to current tools addressing immunonutritional interventions, our system stands out due to its superior performance. By integrating oncological, nutritional, and immunological parameters, it surpasses existing nutritional indices in predicting postoperative adverse events. Moreover, our system targets immunonutritional interventions specifically towards patients who stand to gain the most. Our study's findings suggest that proactively managing inflammation and providing nutritional support early on could enhance the prognosis for cancer patients. Identifying patient status before surgery holds various clinical benefits, including prognostic stratification and tailored treatment. Timely detection and improvement of malnutrition and inflammation have the potential to yield improved outcomes for patients (22).
This study has several limitations that merit consideration. First, the retrospective nature of the study inevitably introduced selection bias, despite the strict adherence to inclusion and exclusion criteria during sample selection. Additionally, the significance of ALRI should be confirmed through validation in other cohorts. Second, the evaluation was based on a relatively small number of patients. Thirdly, confounding factors like infection, ischemia, or acute coronary disease, which could impact serum ALB levels, were not taken into account. Fourthly, the examination of underlying diseases that might influence serum ALB levels, such as liver cirrhosis and chronic renal failure, was not conducted. Fifthly, the optimal cut-off value for the preoperative albumin level and total lymphocyte count remains unknown, despite setting it at 4.0 and 1400 in this study using ROC analysis. Therefore, a large prospective study is warranted to validate and further explore our findings.
In conclusion, this study proposes that preoperative ALRI can function as a straightforward and valuable predictor for gastric cancer prognosis. Furthermore, ALRI can be integrated into preoperative prognosis stratification and postoperative follow-up, contributing to the customization of individualized treatment strategies for CRC.