Serum Alpha-fetoprotein Research Articles

The hepatocyte nuclear factor 1 homeobox A (HNF1A) gene polymorphism and AFP serum levels in Egyptian HCC patients

BackgroundHepatocyte nuclear factors were first identified as liver-enriched transcription factors that might participate in various activities related to the transcription of genes unique to the liver.ObjectiveThe study aimed to reveal the impact of HNF1A gene variations on disease progression in hepatocellular carcinoma (HCC) patients and its relation to serum alpha-fetoprotein level.MethodsParticipants in the study were classified as Group I, 32 HCC patients; Group II, 36 chronic hepatitis C patients; and Group III, 26 healthy volunteers as a control group.Each patient underwent full history taking, thorough clinical examination, and radiological examination. Furthermore, tumor staging was done using BCLC staging system. HNF1A gene polymorphisms (rs 2,464,196 and rs 1,169,310) were genotyped by real-time PCR.ResultsThe findings revealed the highest frequency of AA and GA genotypes of HNF1A (rs2464196) polymorphism in both HCC (P = 0.002) and chronic HCV (P = 0.004) patients in comparison with controls. Regarding rs1169310gene polymorphism, no significant variation was observed across various genotypes when comparing the experimental groups to the control group. Additionally, HCC patients harboring the AA genotype for rs2464196 had significantly increased AFP (≥ 200 ng/ml) levels, whereas HCC patients with rs1169310 SNPs for HNF1A had no significant association regarding the AFP level.ConclusionThe rs2464196 polymorphism of HNF1 is associated with increased AFP levels and HCC disease progression, which may be a prognostic and diagnostic genetic indicator.

Characteristics of HCC patients with portal vein thrombosis: albumin and survival.

Presence of macroscopic portal vein thrombosis (PVT) in patients with hepatocellular carcinoma (HCC) has been found to be a major poor prognosis characteristic. To examine patients with PVT for their clinical characteristics and factors related to both PVT and to survival. A large HCC database containing 1094 patients with PVT and 2513 patients without PVT was examined. Patients had routine baseline serum liver parameters and alpha-fetoprotein (AFP) levels measured; radiological assessment of maximum tumor diameter (MTD), tumor number, presence of macroscopic portal vein thrombosis, plus survival. The percent of patients with PVT increased with increase in both MTD and serum AFP levels and liver parameter levels were worse in patients with PVT than without it. A logistic regression model showed that the combination of MTD>5cm plus AFP >100 IU/mL plus albumin <3.5 g/dL had an odds ratio of 10.988 for the presence of PVT. Normal serum albumin levels significantly reduced the hazard ratio for death in a Cox proportional hazard model and were associated with decreased liver failure. Logistic regression showed the significance of MTD, AFP and albumin on presence of PVT and the Cox model highlighted the importance of albumin levels in decreasing death.

Differences in second trimester risk estimates for trisomy 21 between Maglumi X3/Preaccu and Immulite/Prisca systems

Abstract Objectives Maternal serum alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) or free βHCG, and unconjugated estriol (uE3) concentrations are used to screen trisomy 21 in the second trimester. The performance of different analytical platforms has an impact on individual risk estimates. The aim of this study is to compare the multiple of median (MoM) values and risk estimates generated by Maglumi X3 analyzer/Preaccu software with the Immulite 2000 XPi device/Prisca software. Methods 164 pregnant women (including 20 pregnants with risk estimates above ≥1 in 250 for trisomy 21) analyzed with both platforms. Results Passing–Bablok indicated proportional bias (0.75 [95 % CI 0.70 to 0.82]) between AFP MoMs and both systematic (−0.20 [95 % CI –0.33 to −0.05]) and proportional (1.25 [95 % CI 1.06 to 1.44]) differences between the HCG/free βHCG MoMs, respectively. No significant differences (p=0.070) were present between calculated individual risks by both of the programmes (estimated median risk with Immulite/Prisca system was 1 in 1890 and 1 in 1220 with Maglumi X3/Preaccu system). The triple test result for three pregnant women was negative with the Prisca program, it was positive with the Preaccu. Conclusions Second trimester screening performance of Maglumi X3/Preaccu system achieves comparable performance. Determining regional median values before using will provide more accurate and reliable results.

Diagnostic features of pediatric testicular yolk sac tumors: a 13-year retrospective analysis

BackgroundTesticular yolk sac tumor (YST) is a rare neoplasm with limited practical guidance for preoperative diagnostic assessment. This study aims to conduct a retrospective analysis of the value of clinical profiles and MRI parameters in accurately diagnosing pediatric testicular YST while exploring characteristic indicators for these patients.MethodsThis retrospective study analyzed eighty patients with a testicular mass who underwent surgical treatment and preoperative MRI. Clinical characters (age, preoperative serum alpha-fetoprotein (AFP) levels), and radiology features were recorded and compared. Subsequently, patients were categorized into YST and non-YST groups based on histology. Comparative statistical analyses were then used to compare factors between the two groups. The receiver operating characteristic curve (ROC) analysis was conducted to evaluate the diagnostic performance of the indicators for pediatric testicular YST.ResultsForty patients (50%) were diagnosed with YST. In comparison to the non-YST group, patients with testicular YST were younger and had larger tumor sizes, accompanied by significantly elevated AFP levels. On MRI, most YST cases (n = 38) exhibited predominantly solid lesions, whereas non-YST tumors were more likely to contain cystic components. The bright dot sign and thickened spermatic cord might also be helpful in differentiating YST (p < 0.05). The optimal factor for diagnosing testicular YST was signal intensity, with an AUC value of 0.936 (95%CI: 0.877 ~ 0.995).ConclusionsA predominantly solid testicular mass with a bright dot sign, thickened spermatic cord ipsilaterally, and elevated AFP levels should raise suspicion for YST.

Diagnostic Value of Abnormal Prothrombin for Primary Liver Cancer

Objective: To investigate the diagnostic value of abnormal serum prothrombin levels in hepatocellular carcinoma (HCC). Methods: A total of 298 patients were diagnosed with HCC at Hunan Provincial People’s Hospital between January 1, 2019, and December 31, 2024, through imaging or liver biopsy, along with 100 patients with cirrhosis, 100 patients with chronic hepatitis B virus infection, and 89 healthy controls, were included in the study. Basic demographic information, as well as levels of abnormal serum prothrombin and alpha-fetoprotein (AFP), were collected. The levels of abnormal serum prothrombin and AFP across the four groups were compared, and their diagnostic efficacy for HCC was analyzed using ROC curve analysis. Results: Abnormal prothrombin levels were significantly higher in the liver cancer group compared to the cirrhosis, hepatitis, and healthy control groups (P &lt; 0.05). No significant differences in abnormal serum prothrombin levels were observed among the cirrhosis, hepatitis, and healthy control groups (P &gt; 0.05). Serum AFP levels were significantly higher in the liver cancer group compared to the cirrhosis, hepatitis, and healthy control groups (P &lt; 0.05) and were higher in the hepatitis group compared to the cirrhosis and healthy control groups (P &lt; 0.05). However, no significant difference in AFP levels was found between the cirrhosis and healthy control groups (P &gt; 0.05). ROC curve analysis indicated that the area under the curve (AUC) for abnormal serum prothrombin and AFP in diagnosing HCC was 0.925 (95% CI: 0.901–0.949) and 0.810 (95% CI: 0.775–0.845), respectively, with sensitivities and specificities of 84% and 75% for abnormal prothrombin and 94% and 76% for AFP. For the diagnosis of AFP-negative HCC, the AUC for abnormal serum prothrombin was 0.838 (95% CI: 0.774–0.901), with a sensitivity and specificity of 65% and 95%, respectively. Conclusion: Serum abnormal prothrombin levels are highly expressed in HCC patients and demonstrate strong diagnostic efficacy for HCC.

Serum Alpha-fetoprotein Associated with Treatment Efficacy of Immune Checkpoint Inhibitors in Patients with Hepatocellular Carcinoma: A Meta-Analysis and a Retrospective Cohort Study

Context: Serum alpha-fetoprotein (AFP) has been shown to be valuable in tumor staging and predicting survival outcomes. In this investigation, we conducted a retrospective cohort analysis and a meta-analysis to assess the predictive significance of initial AFP levels in patients with hepatocellular carcinoma (HCC) who underwent treatment with immune checkpoint inhibitors (ICIs). Methods: We searched databases from inception until 14 July 2024 to identify cohort studies involving ICI treatments in HCC patients with baseline AFP data. We also retrospectively analyzed patients with HCC treated with ICIs to assess the therapeutic effect in the high AFP (AFP ≥ 400 ng/mL) group and the low AFP (AFP &lt; 400 ng/mL) group in terms of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Results: In the meta-analysis, a total of 34 studies, comprising 8,799 patients, were included, while the retrospective cohort study encompassed 55 patients. In the meta-analysis, the summarized hazard ratios (HRs) of AFP ≥ 400 ng/mL versus AFP &lt; 400 ng/mL for ICI therapy indicated that the high AFP group had a poorer outcome compared to the low AFP group, with a pooled HR for OS of 1.69 (95% CI: 1.57 - 1.82, P &lt; 0.001) and a pooled HR for PFS of 1.47 (95% CI: 1.33 - 1.63, P &lt; 0.001). In the retrospective cohort study, higher AFP levels were associated with a lower DCR for ICIs, with a DCR of 42.9% in the high AFP group and 77.8% in the low AFP group (P = 0.008). Cox model analysis showed that higher serum AFP was an independent predictor for shorter OS (HR 3.584, 95% CI: 1.466 - 8.762, P = 0.005). The toxicity analysis also displayed a strong association between high AFP and the occurrence of immune-related adverse events (irAEs) (P = 0.008). Conclusions: Higher serum AFP is associated with poorer efficacy of ICI treatment in HCC patients.

Alpha-fetoprotein-producing intramucosal gastric cancer found during examination of metastatic lymph nodes.

Endoscopic resection has been applied as an absolute indication for early gastric cancer showing intramucosal cancer ≤ 2cm in diameter, differentiated-type adenocarcinoma without ulcerative findings. We describe the case of a 76-year-old man who underwent radical gastrectomy for alpha-fetoprotein-producing gastric cancer, in which the depth of invasion was clinically diagnosed as T1a after lymph node metastases were detected. Upper gastrointestinal endoscopy revealed a type 0-IIc tumor nearly 10mm in diameter at the antrum. Computed tomography showed a 47-mm nodule along the common hepatic artery and a 22-mm nodule in the infrapyloric area. Both were pathologically confirmed as adenocarcinoma by endoscopic ultrasound-guided aspiration. No evidence of malignancy elsewhere was seen on 18F-fluorodeoxyglucose positron emission tomography. Serum alpha-fetoprotein level was elevated. Postoperatively, microscopic examination revealed moderately differentiated adenocarcinoma confined to the mucosal layer without lymphovascular involvement. Immunohistochemical examination for alpha-fetoprotein revealed that the metastatic nodes were positive despite the primary tumor being negative. The patient died of exacerbation of myelodysplastic syndrome 5years 8months postoperatively with no recurrence. Our experience suggests the need for further studies to validate whether the indications for endoscopic resection can apply to alpha-fetoprotein-producing gastric cancer in the same manner as to conventional gastric cancer.

Nomogram for predicting testicular yolk sac tumor in children based on age, alpha-fetoprotein, and ultrasonography.

To establish a predictive model for distinguishing testicular benign or yolk sac tumors in children. We retrospectively analyzed data for 119 consecutive patients with unilateral testicular tumors treated at a single institution from June 2014 to July 2020. The patients were divided into the benign (n = 90) and yolk sac (n = 29) tumor groups based on the pathological diagnosis. We recorded patient age, serum markers [serum alpha-fetoprotein (AFP), human chorionic gonadotropin], and tumor ultrasonic findings (maximum diameter, ultrasonic echo, blood flow signal). Predictive factors were identified using descriptive statistical methods. A nomogram was established for preoperative prediction. An additional 46 patients were used as a validation cohort to verify the model. Patients with testicular yolk sac tumors were younger (median age: 14.0 vs. 34.0 months, P = 0.001) and had a higher incidence of elevated AFP levels (93.1% vs. 2.2%, P < 0.001). Ultrasonography indicated that testicular yolk sac tumors tended to have larger maximum diameters (26.5 ± 11.3 vs. 16.6 ± 9.2 cm, P < 0.001), a higher proportion of hypoechoic masses (44.8% vs. 8.9%, P < 0.001), and a higher incidence of masses with strong blood flow signals (93.1% vs. 5.6%, P < 0.001). A nomogram based on age, AFP levels, and ultrasound blood flow signals effectively predicted the probability of yolk sac tumor in children, with an accuracy of 0.98 (95% confidence interval: 0.984-1.003). The Brier score of the nomogram was 0.0002. A nomogram based on age, AFP levels, and ultrasound blood flow signals can effectively predict the probability of testicular yolk sac tumor preoperatively, aiding in clinical decision-making and patient counseling.

CK19 is associated with poor survival in patients with dual-phenotype hepatocellular carcinoma

Objective: To study the role of CK19 in the survival of patients diagnosed with DPHCC in Fujian, China, which has a high incidence of hepatocellular carcinoma (HCC). Methods: Patients with DPHCC (n=84) who had undergone surgical interventions at the 900th Hospital of Joint Logistic Support Force between 2013 and 2019 were retrospectively analyzed using the log-rank test and Kaplan-Meier method. Univariate and multivariate Cox model analyses were also conducted to further understand the correlation between CK19 and patient survival. Results: (1)Tumor size, differentiation, peripheral hepatic fibrosis, liver capsule invasion, microvascular invasion (MVI) and serum CA-199 level showed a correlation with CK19, as per the outcomes of Chi-squared tests. (2)According to the univariate analysis, the expression of CK19, MVI, the number of tumor lesions, necrosis, differentiation, peripheral hepatic fibrosis, and serum levels of both alpha-fetoprotein (AFP) and CA-199 showed a strong correlation with overall survival. (3)Necrosis and serum AFP levels were strongly related to an increased risk of death, according to the multivariate analysis. Conclusions: The expression of CK19 may correlate with the survival of patients with DPHCC and could potentially serve as a prognostic predictor of survival.

Dendritic mesoporous silica loaded with gold nanoclusters and their application in immunochromatographic assay.

Novel green-emitting fluorescent microspheres (GreFMPs) were assembled by loading highly luminescent gold nanoclusters (Arg/ATT/AuNCs) ondendritic mesoporous silica nanoparticles (DMSNs) via PEI-mediated electrostatic adsorption. The fluorescence microspheres exhibit excellent monodispersion with average diameters about (254.5 ± 34.6nm). Compared with free Arg/ATT/AuNCs, the GreFMPs have similar fluorescent properties and biocompatibility but superior environmental tolerance. Subsequently, an immunochromatographic assay based on GreFMPs (GreFMP-ICA) has been successfully developed, which is highly selective toward alphafetoprotein (AFP) in human serum. Under the optimal parameters, there is a good linear range between 0.5 and 160.0ng/mL, the limit of detection was found to be about 0.5ng/mL, and the recovery and relative standard deviation are 81.0 ~ 100.6% and 3.5 ~ 16.6%, respectively. These results manifested that the GreFMPs are beneficial for the rational design of the ICA platform, and the proposed GreFMP-ICA has the potential to screen AFP in clinical applications.

Ovarian Masses in Children: Surgical Experience and Outcomes.

This study aims to review our experience of treating ovarian masses in children with an emphasis on clinical presentation, diagnosis, treatment, and outcome. We retrospectively reviewed the electronic medical records of all patients below 18 years of age who underwent surgical treatment for ovarian masses at our institute between 2009 and 2023. Study variables included demography, clinical presentation, physical findings, tumor markers, radiologic features, operative details, histopathology, follow-up status, and overall survival. During the study period, 30 patients with a mean age of 10.07 years (range: 15 days-18 years) underwent surgical treatment for ovarian masses. Nonneoplastic ovarian masses were seen in 5 (16.7%) patients, whereas 25 (83.3%) patients had benign (10 [33.3%], borderline 3 [10%], or malignant 12 [40%]) ovarian neoplasms. The most common clinical presentation in the benign group was abdominal pain (n = 6), whereas painless abdominal mass (n = 6) was the predominant complaint in children with malignant tumors. A functional ovarian mass presenting with precocious puberty or virilization was seen in 5 (16.7%) patients. On imaging, nonneoplastic and benign lesions had a mean size of 4.33 (range: 3.1-6) cm and 12.63 (range: 2.8-28) cm, respectively, whereas borderline and malignant masses had a mean tumor size of 22.5 (range: 6.5-32) cm and 12.55 (range: 3.5-18.7) cm, respectively (P < 0.05). The cystic component was identified in all nonneoplastic and benign tumors, whereas the solid component was present in all borderline and malignant lesions (P < 0.05). Tumor markers such as serum alpha-fetoprotein and beta-human chorionic gonadotropin were raised in 8 (66.67%) of malignant tumors, whereas markers were normal in all benign lesions and borderline malignant lesions and 4 (33.33%) of malignant tumors. Lactate dehydrogenase (LDH) was also raised in all malignant masses (n = 12), whereas it was normal in all benign and borderline malignant masses (n = 18). In 6 (20%) patients with nonneoplastic and benign masses with maximum tumor size <6 cm, the laparoscopic approach was adopted, whereas open surgery was preferred in the rest of the patients. At a mean follow-up of 53.5 (range: 4-117) months, all patients are alive and disease free. Preoperative imaging characteristics (tumor size and solid component) and raised tumor markers may help us to differentiate between benign and malignant ovarian pathologies. The overall prognosis of pediatric ovarian tumors seems to be favorable.

Role of Serum Alpha-fetoprotein in Assessing the Resectability of Hepatocellular Carcinoma

Background: Serum AFP is a well-established tumor marker of hepatocellular carcinoma (HCC) which has already proved its acceptability in confirming the diagnosis and predicting the prognosis of HCC. Objective: The current study is aimed to evaluate the role of serum alpha-fetoprotein in assessing the resectability of HCC. Methods: This was a single-center, cross-sectional study done from September 2020 to August 2021 at the department of Hepatobiliary, pancreatic, and liver transplantation surgery at BSMMU. A total of 27 HCC patients who met the inclusion criteria were enrolled in the study. Clinical, laboratory, and imaging findings were obtained using a standardized data collecting sheet with the patients' informed agreement. AFP was measured by automated chemiluminescence analyzer (LIAISON XL, DiaSorin, Italy) in the Department of Biochemistry &amp; Molecular Biology, BSMMU. Based on the ROC curve of this study, the patients were divided into group 1 with AFP levels 38.45 ng/ml and group 2 with AFP levels &gt;38.45 ng/ml. According to the resectable criteria (TNM stage: I, II, BCLC stage: 0, A, B, CTP grade: A, B, ECOG PS: 0) established for the study, each AFP group was further subdivided into resectable and unresectable subgroups. Finally, the parameters (tumor size, number, location, CTP grade, fibrosis score, performance status, HBV positive, HBV DNA, BCLC and TNM stage) of the resectable and unresectable patients in each AFP group were evaluated. Statistical analyses were performed using SPSS version 22. Quantitative variables were expressed as mean±standard deviation and examined using an unpaired t-test. The qualitative data were represented by frequencies and percentages, and the Chi-Square test and Fisher exact test (where applicable) were used to determine any correlation. The statistical tests were conducted with a 95% confidence interval, and P0.05 was deemed statistically significant. Results: In this study, thirty seven percent (37%) patients ...........

Prevalence of Low FIB-4 in MASLD-Related Hepatocellular Carcinoma: A Multicentre Study.

Major society guidelines recommend the fibrosis-4 index (FIB-4) as the initial step to risk stratifying people with metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to evaluate the proportion of people with MASLD-related hepatocellular carcinoma (HCC) and a low FIB-4. This cohort study included 613 consecutive adults (33% female) diagnosed with MASLD-related HCC from January 2008 to August 2023 at seven international centres in Australia, India, Japan, South Korea, Singapore and the United States. The primary objective was to determine the proportion of participants with a low FIB-4, defined as FIB-4 < 1.3, or < 2 if age > 65 years, in people without cirrhosis. The mean (±SD) age and body mass index were 71 (±11) years and 27 (±7) kg/m2, respectively. Overall, 235 participants (38%) did not have known cirrhosis. The median FIB-4 was 3.90 (IQR 2.42-6.42). A total of 78 participants (13%) had a low FIB-4. Among participants without known cirrhosis (n = 235), 62 participants (26%) had a low FIB-4. Participants with a low FIB-4 had larger median total tumour diameter (p < 0.001) and lower median serum alpha-fetoprotein (p = 0.005), compared to participants without a low FIB-4. Cirrhosis was associated with lower odds of low FIB-4, but not other factors such as male sex, type 2 diabetes, or obesity. More than a quarter of those with MASLD-related HCC without cirrhosis have a low FIB-4. The proposed clinical care pathways may not identify these people for further evaluation.

Prognostic Role of Serum Vascular Endothelial Growth Factor and Hepatocyte Growth Factor Post Stereotactic Body Radiation in Advanced Hepatocellular Carcinoma

Stereotactic body radiation therapy (SBRT) has evolved as a treatment alternative for advanced hepatocellular carcinoma (HCC) patients who are ineligible for other local therapies. Posttreatment responses are assessed by imaging modalities, serum AFP, and protein induced by vitamin K absence-II (PIVKA) II levels. Despite good specificity, both AFP and PIVKA-II have low to medium sensitivity. The study aimed to find more effective biomarkers that have an impact on the survival outcomes of the patients. We have prospectively collected blood samples from 18 patients undergoing SBRT. Serum levels of hepatocyte growth factor (HGF) and vascular endothelial growth factor-A (VEGF-A) were analyzed kinetically pre-SBRT following day 5 and day 30 post-SBRT. Local control (LC), overall survival (OS), progression free survival (PFS), and postprocedure adverse events were recorded. The cohort had a median follow-up duration of 12.5 months (range 4-30 months). In the entire cohort, the estimated mean OS was 21.2 months (95% confidence interval [CI], 15.9-26.4), and the median progression free survival (mPFS) was 8 months (95% CI, 1.7-14.2). Patients with higher PIVKA-II levels (pre- and post-SBRT) also showed increased concentrations of VEGF-A and HGF. Patients with metastasis at presentation had higher HGF (P=0.028) and VEGF-A (P=0.027) concentrations compared to the nonmetastatic group. Patients with increased levels of VEGF-A and HGF at day 30 post-SBRT compared to day 5 had poor PFS. Indeed, the mPFS was 22 months vs 6 months (P=0.301) in patients with low VEGF-A post SBRT on day 30 compared to day 5. Similarly, mPFS in patients with increase in HGF was 6 months as compared to 22 months (P=0.326) in patients in whom HGF was reduced post-SBRT. We conclude that in addition to PIVKA-II, HGF, and VEGF-A can be used as prognostic and predictive markers for early progression of disease post-SBRT. However, further prospective trials are warranted in the future to validate the results.

Overall Survival of Young Patients with Hepatocellular Carcinoma in Barcelona Clinic Liver Cancer Stage B in a Retrospective Study Based on a Multicenter Cohort.

Hepatocellular carcinoma (HCC) is usually diagnosed in patients at the age of > 45years. We aimed to determine the prognosis of patients with HCC at the age of 30-44years compared with that of patients at a more senior age. Based on the Sun Yat-sen University Cancer Center database, a total of 1745 patients with HCC were retrospectively enrolled and were assigned to three age groups (30-44, 45-59, and 60-70years). The primary endpoint was overall survival. Among baseline characteristics, five variables including sex, serum albumin level, total bilirubin level, the maximum tumor diameter, and the number of tumor nodules were adjusted using propensity score matching. Patients aged 30-44years presented a worse overall survival, a greater number of HCC nodules, a greater maximum tumor diameter, and higher serum alpha-fetoprotein (AFP) concentration than those aged 45-59years in a crude analysis (p < 0.05). Using propensity score matching, the difference in overall survival between the two cohorts was canceled (p > 0.05). The prognosis of patients with HCC at age 30-44years was equal to that of patients aged 45-59years.

Tissue and Imaging Biomarkers of Response to Neoadjuvant Nivolumab or Nivolumab plus Ipilimumab in Patients with Resectable Hepatocellular Carcinoma

Introduction: Perioperative immunotherapy has shown promise in some patients with early-stage hepatocellular carcinoma (HCC). This study examined tissue and imaging biomarkers associated with pathologic response in a phase II clinical trial in patients with resectable HCC. Methods: Analysis included 18 patients with biopsy-proven resectable HCC treated with neoadjuvant nivolumab plus ipilimumab or nivolumab alone in a phase II clinical trial at MD Anderson Cancer Center (NCT03222076). Liver MRE (to measure tissue fibrosis) and biopsies (to evaluate immune activation markers) were obtained serially pretreatment and after completing neoadjuvant immunotherapy. A major pathologic response (MPR) was defined as tumor necrosis of more than 70%. Data comparing patients with MPR versus those without were summarized using descriptive statistics and compared using the Wilcoxon rank-sum test. Results: Patients with MPR after neoadjuvant immunotherapy tended to have larger tumors (mean 9.52 vs. 4.99 centimeters; p = 0.050). They had a significant reduction in tumor size posttreatment (14.67% reduction vs. 9.15% increase in size; p = 0.042) and a nonsignificant decrease in serum AFP (−24.20% vs. −14.00%; p = 0.085). Further, patients with MPR had a greater increase in intratumoral expression levels of CD8 (26.92% vs. −0.04%; p = 0.026), granzyme B (15.56% vs. −2.24%; p = 0.011), and PD-1 (20.17% vs. 0.40%; p = 0.048) but not PD-L1 (7.69% vs. 0.57%; p = 0.26). For imaging biomarkers, tumor and liver fibrosis were comparable before and after neoadjuvant therapy in patients with MPR versus nonresponders. Conclusion: Changes in tumor size, immune cell infiltration, and immune cell activation are candidate predictive markers of pathologic response to neoadjuvant immunotherapy in patients with resectable HCC.

TRIM55 restricts the progression of hepatocellular carcinoma through ubiquitin-proteasome-mediated degradation of NF90

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide. Tripartite motif containing 55 (TRIM55), also known as muscle-specific ring finger 2 (Murf2), belongs to the TRIM protein family and serves as an E3 ligase. Recently, the function and mechanism of TRIM55 in the advancement of solid tumors have been elucidated. However, the role of TRIM55 and its corresponding protein substrates in HCC remains incompletely explored. In this study, we observed a significant reduction in TRIM55 expression in HCC tissues. The downregulation of TRIM55 expression correlated with larger tumor size and elevated serum alpha-fetoprotein (AFP), and predicted unfavorable overall and tumor-free survival. Functional experiments demonstrated that TRIM55 suppressed the proliferation, migration, and invasion of HCC cells in vitro, as well as hindered HCC growth and metastasis in vivo. Additionally, TRIM55 exhibited a suppressive effect on HCC angiogenesis. Mechanistically, TRIM55 interacted with nuclear factor 90 (NF90), a double-stranded RNA-binding protein responsible for regulating mRNA stability and gene transcription, thereby facilitating its degradation via the ubiquitin-proteasome pathway. Furthermore, TRIM55 attenuated the association between NF90 and the mRNA of HIF1α and TGF-β2, consequently reducing their stability and inactivating the HIF1α/VEGF and TGFβ/Smad signaling pathways. In conclusion, our findings unveil the important roles of TRIM55 in suppressing the progression of HCC partly by promoting the degradation of NF90 and subsequently modulating its downstream pathways, including HIF1α/VEGF and TGFβ/Smad signaling.

Preoperative serum glutathione reductase activity and alpha-fetoprotein level are associated with early postoperative recurrence of hepatocellular carcinoma

Abstract Objectives The aim of this study is to investigate the correlation between preoperative serum glutathione reductase (GR) activity, alpha-fetoprotein (AFP) level, and early postoperative recurrence in patients diagnosed with hepatocellular carcinoma (HCC). Methods The data of 91 patients with HCC who underwent hepatectomy at Jinhua Hospital from January 2020 to December 2021 were retrospectively analyzed. A comparison of clinical characteristics between Non-Recurrent group and Recurrence group was conducted, and the association between GR activity, AFP levels, and early postoperative recurrence in HCC was investigated. Results Recurrence group (n=50) had a significantly higher AFP levels (median: 226.7 vs. 99.7 μg/L, p&lt;0.001) and significantly lower GR activity (median: 55.0 vs. 68.0 U/L, p&lt;0.0001) compared with Non-Recurrent group (n=41). The GR activity was negatively correlated with the AFP level (r=−0.4275, p&lt;0.01). Low GR activity (OR=0.948; 95 % CI: 0.910–0.988; p=0.011) and high AFP levels (OR=1.003; 95 % CI: 1.000–1.006; p=0.036) independently contribute to an increased risk of early postoperative recurrence in HCC patients. The area under receiver operating characteristic curve of GR activity and AFP level for predicting early postoperative recurrence of HCC was 0.790 and 0.708, respectively. Patients with GR &gt;60U/L had a higher early postoperative non-recurrence rate than patients with GR ≤60U/L (71.4 % [30/42] vs. 22.4 % [11/49]; HR=4.026; 95 % CI: 2.254–7.188; p&lt;0.01); Patients with AFP ≤100 μg/L had a higher early postoperative non-recurrence rate than patients with AFP &gt;100 μg/L (65.6 % [21/32] vs. 33.9 % [20/59]; HR=2.490; 95 % CI: 1.397–4.438; p&lt;0.01). Conclusions The preoperative serum GR activity and AFP level hold significant predictive value for early postoperative recurrence in HCC patients.

Clinical Rarity Unveiled: Adenocarcinoma with Enteroblastic Differentiation at the Gastroesophageal Junction in a Young Patient - A Diagnostic Challenge Shaping Therapeutic Paradigms

Abstract Introduction/Objective This report details a case of a young patient diagnosed with an adenocarcinoma with enteroblastic differentiation at the gastroesophageal junction (GEJ), characterized by Alpha-Fetoprotein (AFP) production. This manifestation previously rarely documented in young patients (25-44 years old), underscores the critical role of precise pathology diagnosis in guiding effective patient management. Methods/Case Report The patient’s clinical presentation included chest pain, abdominal pain, and weight loss, prompting imaging studies revealing liver masses, lesions in the lung and adrenal gland, and retroperitoneal adenopathy with unremarkable testicular findings. Rapidly progressing dysphagia led to a liver biopsy and esophagogastroduodenoscopy (EGD), where a fungating mass extending from the distal esophagus into the stomach was biopsied. A subsequent serologic test unveiled an elevated serum AFP level (approximally 31, 000 ng/ml). Results (if a Case Study enter NA) Histological examination revealed similarities between the liver and distal esophageal tumors, characterized by moderately differentiated carcinoma with solid and glandular growth patterns. The tumor cells, resembling fetal gut epithelium, exhibited positive immunostaining for SALL4, AFP, CK8-18, CK19, and CDX2. A diagnosis of adenocarcinoma with enteroblastic differentiation at the GEJ was determined, correlating with clinical and radiological assessments. Despite initiating one cycle of gastrointestinal related chemotherapy, the patient succumbed to tumor lysis syndrome within a month of diagnosis. Conclusion This case highlights the critical need for a comprehensive differential diagnosis when encountering young patients with AFP-producing malignancies. Although metastatic non-seminomatous germ cell cancer is a primary consideration, upper gastrointestinal adenocarcinoma with unique characteristics, as demonstrated in this case, requires distinct therapeutic approaches, emphasizing the importance of accurate and timely diagnosis.

Electrochemical immunosensor based on PtNPs/MoS2@rGO composite for the detection of alpha-fetoprotein in human serum.

An electrochemical biosensor was created to identify the liver cancer marker alpha-fetoprotein (AFP) by employing nanocomposite materials. Acombination of reduced graphene oxide (rGO) and molybdenum disulfide (MoS2) was selected as the substrate material for the sensor to prepare the PtNPs/MoS2@rGO electrochemical immunosensor. Among them, rGO has strong conductivity and MoS2 provides a large surface area for the anchoring of PtNPs for better attachment to the hybridized nanomaterials. Meanwhile, PtNPs exhibit consistent biocompatibility and excellent electrocatalytic activity. PtNPs also attach to hybrid nanomaterials and bind the antibody via the Pt-S bond, thereby furnishing the antibody with multiple binding sites for enhanced antibody adhesion. The immunosensor achieved ultra-sensitive AFP detection by exploiting the specific antigen-antibody binding. The structure and morphology of the PtNPs/MoS2@rGO composites were investigated by transmission electron microscopy (TEM), energy dispersive X-ray (EDS) spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy, and the sensor was electrochemically characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy(EIS). Under optimized conditions, using differential pulse voltammetry the biosensordetected AFP in serum within a linear range of 1 ~ 105pg/mL, with a correlation coefficient (r2) of 0.9989, and a detection limit of 0.12pg/mL (S/N = 3). The method offers a new approach for the ultrasensitive detection of serum AFP and is extremely selective, accurate, and precisewith a relative standard deviation (RSD) of less than 6%. It has been successfully appliedto the analysisof real human blood samples.