Serum ZFPL1 as a clinical biomarker for diagnosis, progression tracking, and treatment response in lung cancer.

[OBJECTIVE] Zinc finger protein-like protein 1 (ZFPL1) is a key protein involved in various biological processes such as cell growth, migration, proliferation, and metabolism. It plays a significant role in the development and progression of multiple malignancies, including endometrial cancer and gastric cancer. However, research on ZFPL1 in lung cancer remains relatively limited. This study aimed to investigate the clinical application value of serum ZFPL1 in the diagnosis, disease monitoring, and therapeutic evaluation of lung cancer by detecting its expression levels in the peripheral blood of lung cancer patients using enzyme-linked immunosorbent assay (ELISA).

[METHODS] Serum ZFPL1 levels were measured by ELISA in 75 lung cancer patients (including 32 cases of lung adenocarcinoma, 31 cases of squamous cell carcinoma, and 12 cases of small cell lung cancer) and 75 healthy controls. Differences in serum ZFPL1 expression were analyzed based on various clinical characteristics (gender, age, smoking history, pathological type, tumor location, and TNM stage). Bioinformatics analysis was performed to explore ZFPL1-related signaling pathways. Serum ZFPL1 levels were dynamically monitored before and after treatment in 57 patients receiving two chemotherapy cycles and 18 patients undergoing surgery. The diagnostic efficacy of serum ZFPL1 for different types and stages of lung cancer was evaluated using receiver operating characteristic (ROC) curve analysis.

[RESULTS] Serum ZFPL1 levels showed no significant differences among lung cancer patients stratified by gender, age, smoking history, pathological type, or tumor location. Bioinformatics analysis revealed that ZFPL1 was significantly enriched in pro-oncogenic signaling pathways such as mTORC1, E2F, MYC, PI3K/Akt, and the reactive oxygen species pathway. Serum ZFPL1 levels were significantly higher in the lung cancer group than in the healthy control group (P < 0.05) and paradoxically higher in early stages (I-II) vs. advanced (III-IV). Both chemotherapy and surgical treatment significantly reduced serum ZFPL1 levels (P < 0.05). The objective response rate (ORR) and disease control rate (DCR) in the chemotherapy group were 17.54 % and 89.47 %, respectively, while the surgical group achieved a 100 % efficacy rate. The area under the ROC curve (AUC) for serum ZFPL1 in diagnosing lung cancer was 0.921 (sensitivity 78.67 %, specificity 98.67 %). The AUC values for diagnosing lung adenocarcinoma, squamous cell carcinoma, and small cell lung cancer were 0.920, 0.912, and 0.951, respectively. The AUC for differentiating early-stage from mid-to-late-stage lung cancer was 0.657 (sensitivity 91.23 %, specificity 44.44 %).

[CONCLUSION] Serum ZFPL1 may serve as a novel serological biomarker for lung cancer diagnosis. Changes in serum ZFPL1 levels can effectively evaluate the efficacy of chemotherapy and surgical treatment, and serum ZFPL1 has potential predictive value for disease progression in lung cancer.