Evaluation of PDZD11 in hepatocellular carcinoma: prognostic value and diagnostic potential in combination with AFP

Abstract

Background: Hepatocellular carcinoma (HCC) is the most prevalent liver cancer, with a 5-year survival rate below 20% and an average survival time of 3-6 months. Identifying new biomarkers is crucial for early diagnosis and prognosis. The function of PDZ domain protein 11 (PDZD11) in HCC remains unclear.

Methods: In this study, PDZD11 was investigated as a potential biomarker for HCC using bioinformatic analysis of the TCGA and ICGC datasets. Furthermore, we assessed the potential of serum PDZD11 as a clinical diagnostic marker by enrolling a cohort comprising 78 HCC patients and 62 healthy controls (HC) using the ELISA analysis and combining its expression with common tumor markers.

Results: Our research found significantly higher PDZD11 mRNA expression in HCC tissues compared to tumor-adjacent tissues (p < 0.001), which was associated with lower overall survival (OS) rates (p < 0.01). Multivariate evaluation methods established PDZD11 as a standalone predictor of prognosis. A nomogram incorporating PDZD11 expression and clinicopathological factors predicted OS rates for HCC patients over various years. Patients with HCC exhibited notably elevated serum PDZD11 levels compared to HC, with these levels rising further in advanced disease stages and deteriorating performance status (PS). ROC analysis showed high diagnostic accuracy when PDZD11 is combined with AFP (AUC = 0.958).

Conclusion: PDZD11 is more sensitive than AFP in assessing HCC prognosis. In conclusion, PDZD11 is a promising supplementary biomarker for HCC diagnosis and prognosis alongside AFP.

Keywords: AFP; PDZD11; hepatocellular carcinoma; prognosis; serological biomarker.

Figure 1

Elevated levels of PDZD11 were indicative of a poor prognosis in HCC. (A) Boxplot depicting PDZD11 expression levels in HCC versus adjacent tissues from the TCGA dataset. (B) Pairwise boxplot depicting the comparative expression of PDZD11 between HCC and adjacent tissues in the TCGA dataset. (C) Kaplan-Meier survival analysis of PDZD11 utilizing the TCGA dataset. (D) An analysis of the ICGC dataset to examine the effects of PDZD11 expression in patients with HCC on OS. (E) The ROC curve illustrated the diagnostic value of PDZD11 in HCC patients.

Figure 2

To explore the link between PDZD11 levels and OS in HCC patients, both univariate (A) and multivariate (B) COX proportional hazards models were utilized.

Figure 3

A nomogram for predicting OS in patients with HCC. (A) Development of a nomogram incorporating PDZD11 and clinicopathologic variables. For each patient, two lines were drawn to get points from the predictors (stage and PDZD11) in the nomogram. These points were summed and located on the ‘Total Points’ axis. A line was then drawn downwards to determine the 1-, 3-, and 5-year overall survival probabilities for HCC. (B) Calibration curves for 1-year predictions. (C) Calibration curves for 3-year predictions. (D) Calibration curves for 5-year predictions. Nomogram-predicted survival could be visualized on the X-axis, while actual survival can be seen on the Y-axis.

Figure 4

The expression levels of serum PDZD11 in HCC by subgroup. (A) Serum PDZD11 levels in HCC and HC groups. (B) Serum PDZD11 levels across various clinical stages of HCC. (C) Serum PDZD11 levels in HCC patients stratified by performance status. Statistical significance was used by the Mann–Whitney U-test. ****p < 0.0001.

Figure 5

The role of serum PDZD11 levels in the diagnosis and evaluation of therapeutic response. (A) The performance of PDZD11 and AFP in ROC curve analysis for the diagnosis of HCC. (B) Analysis of clinical indices linked to PDZD11 expression using PCA in groups with high and low expression levels. (C) Univariate logistic regression analysis of PDZD11 levels and clinical indices. (D) Comparison of serum PDZD11 levels pre- and post-progression. (E) Monitoring of the HCC patient using PDZD11 and AFP analysis in conjunction with the abdominal CT. The lesion on the abdominal CT was indicated by a red arrow. ***p < 0.0001.