The outcomes and prognostic factors of patients with hepatocellular carcinoma and normal serum alpha fetoprotein levels

Fu, Chia-Chu; Wei, Changyuan; Chu, Chi‐Jen; Lee, Pei‐Chang; Huo, Teh–Ia; Huang, Yi Hsiang; Chao, Yee; Hou, Ming‐Chih; Wu, Jaw‐Ching; Su, Chien–Wei

doi:10.1016/j.jfma.2022.11.006

Cited by 7 publications

(5 citation statements)

References 40 publications

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“…Fifth, in our study, the treatment modality emerged as a significant parameter in determining the OS of patients with early-stage HCC. The results were consistent with previous studies [ 9 , 10 , 49 ]. However, the proportion of patients receiving non-curative treatment modalities was relatively small, potentially impacting the significance of our analysis.…”

Section: Discussionsupporting

confidence: 94%

“…The results were consistent with previous studies. 9,10,49 However, the proportion of patients receiving non-curative treatment modalities was relatively small, potentially impacting the significance of our analysis. Lastly, some of the biomarkers involved in this study still lack universal acknowledgement of cutoff values and clinical applicability.…”

Section: Discussionmentioning

confidence: 99%

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Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma

Ho,

Tan,

Lee

et al. 2024

Clin Mol Hepatol

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma

Ho,

Tan,

Lee

et al. 2024

Clin Mol Hepatol

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“…Tumor markers play a crucial role in the diagnosis and prognosis of various cancers. In the context of HCC, AFP is the most extensively utilized biomarker for both diagnosis and prognostication [ 54 ]. Our study demonstrated a positive correlation of AFP levels and MKi67 expression in the TCGA cohort but not in the GSE76427.…”

Section: Discussionmentioning

confidence: 99%

High Ki67 Gene Expression Is Associated With Aggressive Phenotype in Hepatocellular Carcinoma

Ramos-Santillan,

Oshi,

Nelson

et al. 2024

World J Oncol

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Background Hepatocellular carcinoma (HCC) with high Ki67 protein expression, the most commonly used cell proliferation marker, is associated with an aggressive biologic phenotype; however, conventional immunostaining is hampered by variability in institutional protocol, specific antibody probe, and by assessor subjectivity. To this end, we hypothesized that Ki67 gene ( MKi67 ) expression would identify highly proliferative HCC, and clarify its association with oncologic outcome, tumor progression, and immune cell population in the tumor microenvironment (TME). Furthermore, we sought to identify the cell-cycle gene expression profile that confers this aggressive phenotype. Methods A total of 473 HCC patients with clinicopathological data associated with transcriptome were selected for this study: 358 patients from The Cancer Genome Atlas (TCGA) as the testing cohort, and 115 from GSE76427 as the validation cohort. Each cohort was divided into a highly proliferative group (MKi67-high) and the low MKi67 group (MKi67-low) by the median of Ki67 gene ( MKi67 ) expression levels. Results MKi67-high HCC patients had worse disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) independent of histological grade in the TCGA cohort. MKi67 expression correlated with histological grade and tumor size. MKi67 expression increased throughout the HCC carcinomatous sequence from normal liver, cirrhotic liver, early HCC, and advanced HCC. MKi67-high HCC was associated with higher intratumor heterogeneity, homologous recombination deficiency, and altered fraction as well as intratumoral infiltration of T helper type 1 (Th1) and Th2 cells, but lower interferon-gamma response and M2 macrophage infiltration. Cell proliferation-related gene sets in the Hallmark collection (E2F targets, G2M checkpoint, Myc target v1 and mitotic spindle), MTORC1 signaling, DNA repair, PI3K MTOR signaling, and unfolded protein response were all enriched in the MKi67-high HCC (false discovery rate (FDR) < 0.25). Conclusions High MKi67 gene expression identified highly proliferative HCC with aggressive biology involving classical pathways in cell cycle regulation and DNA repair, as well as poor overall oncologic outcomes. This suggests potential for personalized treatment strategies, but validation and refinement of these observations require further research to elucidate the underlying mechanisms and validate therapeutic targeting of these pathways in MKi67-high HCC tumors.

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“…All the demographic characteristics, baseline laboratory data, tumor factors, treatments, and outcomes of the enrolled patients were prospectively collected in the HCC registration system ( 22 – 25 ). We continued to follow-up the patients until patients had dead or lost to follow-up.…”

Section: Methodsmentioning

confidence: 99%

Prognostic nutritional index as a prognostic factor for very early-stage hepatocellular carcinoma

Ho,

Chia-Hui Tan,

Lee

et al. 2024

Clin Transl Gastroenterol

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Introduction: Field factors play more important roles in predicting the outcomes of patients compared with tumor factors in early-stage hepatocellular carcinoma (HCC). However, the prognostic ability of non-invasive serum marker scores for hepatic fibrosis and liver functional reserve on very early-stage HCC is still not yet determined. We aimed to investigate the performance of these serum marker scores in predicting the prognoses of patients with very early-stage HCC. Methods: A total of 446 patients with the very early-stage HCC from 2012 to 2022 were retrospectively enrolled. Serum biomarkers and prognostic scores determining overall survival (OS) were analyzed by Cox proportional hazards model. We compared the Akaike information criterion (AIC) among the prognostic nutritional index (PNI), AST to Platelet Ratio Index (APRI), albumin-bilirubin (ALBI) score, EZ (easy)-ALBI score, modified ALBI score, fibrosis (FIB)-4 score and lymphocyte-to-monocyte ratio (LMR) to determine the predictability on the OS. Results: After a median follow-up of 41.0 months (interquartile range IQR 36.9-45.1 months), 81 patients died, with a 5-year OS rate of 71.0%. Among the non-invasive serum marker scores, PNI had the best performance in predicting the OS with the lowest AIC (846.407) compared to other scores. Moreover, we stratified the patients into high-risk (PNI<45) and low-risk (PNI>=45) groups. It showed that the 5-year OS rates were 83.4% and 60.8% in the low-risk and high-risk PNI groups, respectively (p<0.001). Conclusions: PNI had the best performance in predicting the OS for patients with very early-stage HCC.

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The outcomes and prognostic factors of patients with hepatocellular carcinoma and normal serum alpha fetoprotein levels

Cited by 7 publications

References 40 publications

Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma

Conventional and machine learning-based risk scores for patients with early-stage hepatocellular carcinoma

High Ki67 Gene Expression Is Associated With Aggressive Phenotype in Hepatocellular Carcinoma

Prognostic nutritional index as a prognostic factor for very early-stage hepatocellular carcinoma

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