Colorectal cancer (CRC) is the second most common malignant tumor in terms of incidence worldwide. Studies have shown that iron metabolism is involved in multiple aspects of tumor progression, such as tumor cell proliferation and immune microenvironment regulation. Clinically, most CRC patients are accompanied by abnormal serum iron status, among which low serum iron levels are more common. Exploring the correlation between low iron status and colorectal cancer is of great significance for the individualized treatment of colorectal cancer.

This study aims to comprehensively and systematically investigate the relationship between the internal environment low iron status and various clinical characteristics in patients with colorectal adenocarcinoma.

Based on a single-center registered retrospective cohort study, 712 patients who were pathologically diagnosed with colorectal adenocarcinoma after surgery at Sichuan Cancer Hospital from January 2017 to June 2023 were consecutively included as research subjects. Indicators including serum iron, transferrin saturation, and various clinical characteristics were collected. Patients were divided into the low iron status group (low iron group, n=363) and the control group with normal iron status (n=349) according to the preoperative serum iron expression level. Propensity score matching (PSM) was used for 1∶1 matching of patients, with a caliper set at 0.2. Finally, 698 matched samples were included (349 cases in both the low iron group and the control group). Univariate and multivariate Logistic regression analysis were used to explore the correlation between low iron status and clinical characteristics.

Among the 712 patients, 363 cases (50.98%) had low iron status in the internal environment. Before PSM matching, there were statistically significant differences between the control group and the low iron group in the American Society of Anesthesiologists (ASA) classification, the proportion of cancer obstruction, and the proportion of anemia (P<0.05); after PSM matching, the differences in ASA classification, the proportion of cancer obstruction, and the proportion of anemia between the two groups were still statistically significant (P<0.05). After PSM, the expression levels of white blood cell count (WBC), C-reactive protein (CRP), plateletcrit (PCT), and carcinoembryonic antigen (CEA) in the low iron status group were higher than those in the control group, while the levels of lymphocyte count (LY), albumin (ALB), and serum total cholesterol (TC) were lower than those in the control group (P<0.05). Before and after PSM, there were statistically significant differences between the two groups in tumor location, International Union Against Cancer (UICC) TNM stage, degree of differentiation, mismatch repair (MMR) expression status, microsatellite stability status, nerve and vascular invasion, liver and lung metastasis rates, and tumor length (P<0.05). After controlling for baseline confounding factors using PSM, anemia was separated as an independent predictive variable for multivariate Logistic regression analysis. The results showed that when anemia was not included, tumor location rectum (OR=0.41, 95%CI=0.25-0.67, P<0.01), UICC stageⅣ (OR=3.50, 95%CI=1.65-7.82, P<0.01), vascular invasion (OR=1.63, 95%CI=1.01-2.63, P=0.04), tumor length (OR=1.16, 95%CI=1.03-1.30, P<0.01), ALB (OR=0.90, 95%CI=0.85-0.95, P<0.01), PCT (OR=1.12, 95%CI=1.08-1.15, P<0.01), and LY (OR=0.51, 95%CI=0.35-0.72, P<0.01) were independent influencing factors for low iron status in patients with colorectal adenocarcinoma. When anemia was included in the multivariate Logistic regression analysis, anemia (OR=7.03, 95%CI=4.40-11.25, P<0.01) became an independent influencing factor for low iron status, while tumor location was no longer an independent influencing factor. The remaining factors, including tumor length, UICC stageⅣ, vascular invasion, and peripheral blood LY, PCT, and ALB, were still independent factors associated with low iron status in patients with colorectal adenocarcinoma (P<0.05).

The internal environment iron status of patients with colorectal adenocarcinoma is closely associated with tumor invasiveness (including tumor stage, neurovascular invasion, and tumor length) as well as inflammatory indicators. Rectal tumor location, along with higher levels of ALB and LY, are protective factors against low iron status in patients with colorectal adenocarcinoma. In contrast, anemia, UICC stageⅣ, vascular invasion, longer tumor length, and higher PCT are risk factors for low iron status.