Clinical significance of immune cell and biomarker changes in liver cancer

Primary liver cancer (PLC) is characterized by high malignancy, rapid disease progression, and persistent high incidence and mortality rates, posing a significant public health challenge worldwide. Early diagnosis and assessment of PLC are of great significance for guiding clinical treatment and improving patient prognosis. Alpha fetoprotein (AFP) and gamma-glutamyl transpeptidase (GGT) are commonly utilized tumor markers for the clinical diagnosis of PLC. They are ideal indicators for the detection of metastasis and recurrence after LC surgery. Nevertheless, not all patients with PLC secrete large amounts of AFP and GGT, which affects the accuracy of evaluating PLC by monitoring these two tumor markers alone. Cluster of differentiation 3 and 161 double-positive natural killer T (CD3⁺CD161⁺NKT) cell subsets are a class of molecules inextricably related to immune function and tumor occurrence and development. This research seeks to explore the clinical significance of CD3⁺CD161⁺NKT cell subsets combined with tumor markers AFP and GGT in the diagnosis of patients with PLC.

To probe the clinical significance of CD3⁺CD161⁺NKT cell subsets and AFP and GGT changes in the peripheral blood of individuals with PLC.

The PLC group comprised 30 patients diagnosed with PLC who were admitted to our hospital between July 2022 and December 2023, whereas the control group consisted of 30 healthy individuals undergoing routine physical examinations at our hospital. Peripheral blood samples were harvested from both cohorts of patients. The levels of CD4⁺NKT, CD8⁺NKT, CD3⁺CD56⁺NKT, CD8⁺CD56⁺NKT, CD3⁺CD161⁺NKT, and CD3^-CD161⁺NKT were measured by flow cytometry. Serum AFP content was determined using a fully automatic immunoassay analyzer, and serum GGT content was ascertained by a fully automatic biochemical analyzer. The diagnostic value of CD3⁺CD161⁺NKT cell subsets and AFP and GGT level alterations for PLC was evaluated by receiver operating characteristic curve analysis.

No significant disparities were observed in the counts of white blood cells, neutrophils, and platelets, as well as the levels of blood urea nitrogen and serum creatinine between the two groups (P > 0.05). Lymphocytes, red blood cells, hemoglobin, total protein, albumin, and globulin were more attenuated in the PLC group than in the control group, while glutamic-pyruvic transaminase, glutamic oxalacetic transaminase, and carcinoembryonic antigen levels were increased in the PLC cohort compared with the control cohort, with statistical significance (P < 0.05). No substantial difference was discovered in peripheral blood CD4⁺NKT, CD8⁺NKT, and CD3⁺CD56⁺NKT cells between the two cohorts (P > 0.05). The percentage of CD8⁺CD56⁺NKT cells (8.35% ± 1.01%), CD3⁺CD161⁺NKT cells (14.36% ± 1.55%), and CD3^-CD161⁺NKT cells (12.08% ± 1.34%) in the PLC group was higher than that in the control group (P < 0.05). The levels of AFP (335.71 ± 20.89 ng/mL) and GGT (136.87 ± 15.62 U/mL) in the PLC cohort were elevated within the PLC cohort compared with the control cohort (P < 0.05). The sensitivity of CD8⁺CD56⁺NKT, CD3⁺CD161⁺NKT, CD3^-CD161⁺NKT, AFP, and GGT alone for diagnosing PLC was 70.00%, 83.33%, 80.00%, 56.67%, and 53.33%, respectively (P < 0.05), with specificity rates of 66.67%, 80.00%, 76.67%, 76.67%, and 66.67%, respectively (P < 0.05). The area under the curve for combined detection was 0.898, with a sensitivity of 86.67% and a specificity of 80.00% (P < 0.05).

The levels of CD8⁺CD56⁺NKT, CD3⁺CD161⁺NKT, CD3^-CD161⁺NKT, AFP, and GGT in the peripheral blood of patients with PLC were markedly elevated. The combined detection of these five indicators can improve the sensitivity and specificity of PLC diagnosis, providing solid evidence for the early clinical diagnosis of PLC.