Low Cholinesterase Is a Potential Poor Prognostic Factor in Colorectal Cancer Presenting With Tumor Markers Negative

Background

Colorectal cancer (CRC) is the third most common malignant tumor in the world and has the second highest mortality rate. Tumor markers are proteins used to diagnose and monitor cancer. Serum cholinesterase (CHE) is a nutritional indicator indicating the liver''s ability to synthesize proteins and is a predictor of CRC. Butyrylcholinesterase (BCHE), a CHE enzyme encoded by the BCHE gene, is synthesized by the liver and released into the serum.

Objective

To study the association between CHE and survival prognosis in CRC with tumor markers negative (TMN). The relationship between the BCHE gene and immune cell infiltration was also explored.

Methods

The clinical data of patients with CRC were collected. The data included tumor markers and biochemical indicators. Patients were divided into different groups for prognosis analysis. CHE levels were used as the cutoff for classification. Further analysis was conducted on the all-TMN group. CHE was found to be correlated with survival prognosis. This study also analyzed BCHE gene expression in cancer and normal tissues. A correlation analysis was conducted with other factors.

Results

(1) Among 1140 patients who met the criteria, the TMN group (n = 369) had a higher survival rate (89.7%) than the TMP group (n = 771, 83.3%; p = 0.035). (2) Among 1140 CHE, the low cholinesterase (CHE^Low) group (n = 165) had worse survival (73.9%) compared to the high cholinesterase (CHE^High) group (n = 975, 87.3%; p < 0.001). (3) In the TMN group, CHE^Low (n = 48) had worse survival (79.2%) than CHE^High (n = 321, 91.3%; p = 0.008). Similarly, in the TMP group, CHE^Low (n = 117) showed poorer survival (71.8%) compared to CHE^High (n = 654, 85.3%; p < 0.001). (4) In colorectal cancer with all TMN, CHE ≤ 5.4 U/L, BMI < 18.5 kg/m², and pN2 were independent detrimental prognostic factors for overall survival (OS) (p < 0.05). (5) BCHE expression differs between cancer and normal CRC tissues. BCHE expression correlated with pathological stage and progression-free survival. BCHE expression positively correlated with immune cell infiltration (p = 2.7e⁻²⁸, r = 0.59), distinctively M2 macrophage infiltration (p < 0.0001).

Conclusion

In CRC with TMN, CHE is an independent detrimental prognostic factor. BCHE may serve as a biomarker for CRC to help predict its prognosis and may have an essential impact on immunotherapy.