1.Application value of human epididymis protein 4 in the diagnosis and treatment of lung cancer
Yang YANG ; Kairu NI ; Chenhui GAO ; Hong HUANG ; Yizhen SHI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(10):597-602
Objective:To analyze the advantages of human epididymis protein 4 (HE4) compared with traditional tumor markers in the diagnosis and treatment of lung cancer.Methods:From February 2021 to June 2022, 230 lung cancer patients (138 males, 92 females; age (61.1±12.3) years), 96 benign lung disease patients (62 males, 34 females; age (60.2±14.8) years; including 43 cases of lung benign placeholder and 53 cases of pulmonary infection), and 60 healthy volunteers (40 males, 20 females; age (62.8±11.4) years) from the Second Affiliated Hospital of Soochow University were prospectively collected. Serum HE4, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cytokeratin 19 fragment (CYFRA21-1), pro-gastrin-releasing peptide (ProGRP) and carbohydrate antigen (CA)125 were detected by electrochemical analysis. The expression of HE4 in tumor tissues of 55 patients with lung cancer was detected by immunohistochemical method. χ2 test, Mann-Whitney U test, Kruskal-Wallis rank sum test and Bonferroni correction method were used to analyze data. The diagnostic efficiencies of HE4 and other tumor markers were evaluated by ROC curve analysis and the difference of AUCs was analyzed by Delong test. Results:The positive expression rate of HE4 in adenocarcinoma tissue was significantly higher than that in non-adenocarcinoma tissue (93.1%(27/29) vs 23.1% (6/26); χ2=28.01, P<0.001). The level of serum HE4 in the lung cancer group (70.70(51.93, 109.05) pmol/L) was significantly higher than that in the pulmonary benign placeholder group (59.80(48.20, 73.50) pmol/L) and the healthy control group (55.25(44.60, 74.25) pmol/L), and that in the pulmonary infection group (97.90(76.62, 155.00) pmol/L) was higher than that in the lung cancer group ( H=46.19, all P<0.008 (Bonferroni correction method)). The levels of serum HE4 were significantly different in age, sex, smoking, disease stage and pathological types in early stage ( z values: from -5.07 to 9.83, all P<0.05). The ROC curve analysis indicated that the optimal cut-off value of serum HE4 for diagnosing lung cancer was 79.22 pmol/L, with the sensitivity and specificity of 41.30%(95/230) and 83.33%(50/60). Compared with other traditional tumor markers, serum HE4 and CA125 showed the higher diagnostic value (AUC CA125 (0.695)>AUC HE4(0.656)>AUC CEA(0.614)>AUC CYFRA21-1(0.599)>AUC ProGRP (0.501)>AUC NSE (0.470)). The combination of HE4 with other traditional tumor markers significantly improved the diagnostic efficacy (AUC=0.750; z=2.75, P=0.006). Conclusions:HE4 is highly expressed in lung adenocarcinoma by immunohistochemistry. Serum HE4 exhibits a great application value in the differential diagnosis between benign and malignant pulmonary nodules, and plays an important role in assessment of patients′ conditions.
2.Preliminary exploration of the relationship between the serum anti-Müllerian hormone and the related clinical factors
Chenhui LEI ; Kairu NI ; Lijuan WU ; Shijian YAN ; Hong ZHANG ; Yizhen SHI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2022;42(4):221-225
Objective:To explore the relationship between serum anti-Müllerian hormone (AMH) level and related clinical factors in healthy females, and establish and validate equation of correlation between age and serum AMH level for healthy females.Methods:From March 2015 to December 2016, a total of 602 females who measured serum AMH level in Department of Nuclear Medicine, the Second Affiliated Hospital of Soochow University were retrospectively enrolled. All cases had relatively complete clinical data, and were divided into healthy group (484 cases, 20-52 years) and case group (118 cases, 20-42 years; patients with menstrual disorders). Relationships between serum AMH level and estradiol (E2), tesosterone (T), follicle stimulating hormone (FSH), luetinizing hormone (LH), body mass index (BMI) of healthy group were analyzed by Spearman rank correlation. Kruskal-Wallis rank sum test was used to analyze the relationship between history of gestation and serum AMH level. Serum AMH level of health group was processed to establish predictive equation for serum AMH level. Internal ( n=27) and external ( n=37) validation group were chosen from healthy females with serum AMH level measured to validate the equation, and signed rank test was used to analyze the data. Difference between serum AMH level in case group and healthy group with corresponding age was explored by independent-sample t test. Results:Serum AMH levels were positively correlated with E2 and T ( rs values: 0.263, 0.334, both P<0.001), and negatively correlated with FSH, LH, BMI ( rs values: from -0.515 to -0.110, all P<0.005). Predictive equation was established as LogAMH=-1.208+ 0.1×age-0.000 042×age 3 ( R2=0.735, P<0.001). No statistically significant difference was found between real serum AMH levels and calculated serum AMH levels in the internal and external validation groups ( z values: -1.62 and -1.52, both P>0.05). Females in case group ( n=118) and control group ( n=446) were divided into two sub-groups respectively (<35 years and ≥35 years), and serum AMH levels of case group were lower than those of control group with corresponding age ( t values: 18.64, 11.70, both P<0.001). Conclusions:In healthy females, serum AMH level is related to some clinical data. The equation between serum AMH level and age established in the study may provide reference for clinical diagnosis and treatment.
3.Preclinical study of a novel molecular probe 89Zr DFO-G4C2 for monitoring PD-1 expression levels
Yirong ZHU ; Weiwei KONG ; Jiaxi YOU ; Kairu NI ; Bing ZHANG ; Zengli LIU ; Yizhen SHI ; Zhihui HONG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(10):603-608
Objective:To design and synthesize 89Zr-deferoxamine(DFO)-G4C2, a novel molecular probe targeting programmed cell death receptor 1(PD-1), and evaluate its in vivo biodistribution and microPET/CT imaging characteristics in tumor-bearing mice. Methods:DFO-G4C2 was prepared by coupling DFO with G4C2, a monoclonal antibody targeting PD-1. The affinity and binding specificity of this amalgamation were subsequently assessed through the implementation of flow cytometry and surface plasmon resonance techniques. The molecular probe 89Zr-DFO-G4C2 was achieved by labeling DFO-G4C2 with the radioisotope 89Zr, and the labeling efficiency and in vitro stability of 89Zr-DFO-G4C2 were determined. Mouse models laden with CT26 colorectal cancer cells expressing PD-1 were established, followed by in vivo biodistribution and microPET/CT imaging studies, to explore the potential clinical value of 89Zr-DFO-G4C2. Additionally, the validity of this molecular probe was verified in 4T1 breast cancer models, affirming its efficacy as an imaging tool across different tumor models. Independent-sample t test was used to analyze the data. Results:DFO-G4C2 exhibited an affinity constant KD of (0.55±0.02) μmol/L, indicating a strong binding affinity. The binding rate to mouse PD-1 protein was determined to be (61.82±8.49)%. The labeling rate of 89Zr-DFO-G4C2 reached a high level of (98.76±0.51)%. Furthermore, the labeling rates in lysate and human serum after 144 h were measured to be (93.07±2.16)% and (83.42±3.21)%, respectively. MicroPET/CT imaging of CT26 tumor-bearing mice injected with 89Zr-DFO-G4C2 showcased pronounced radioactivity uptake in the tumor tissue. At 72 h post-injection, the tumor uptake value reached (10.47±0.34) percentage activity of injection dose per gram of tissue (%ID/g). The tumor uptake observed in the blocked experimental group, wherein an excess of unlabeled antibody was administered, was significantly lower at (6.26±1.03) %ID/g in comparison to the non-blocked group ( t=6.67, P=0.003). The in vivo biodistribution results were consistent with the observed microPET/CT imaging outcomes. MicroPET/CT imaging observations in the 4T1 breast cancer bearing mouse model were analogous to those obtained from the CT26 model. Conclusion:ImmunoPET based on the 89Zr-DFO-G4C2 molecular probe can non-invasively and visually assess the PD-1 expression level of tumors in vivo, and it is expected to be a new molecular imaging technique for immunotherapy monitoring of PD-1 inhibitors.