Dataset Information

Specific gut microbiome signature predicts hepatitis B virus-related hepatocellular carcinoma patients with microvascular invasion.

ABSTRACT:

Background

We aimed to assess differences in intestinal microflora between patients with operable hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) with microvascular invasion (MVI) and those without MVI. Additionally, we investigated the potential of the microbiome as a non-invasive biomarker for patients with MVI.

Methods

We analyzed the preoperative gut microbiomes (GMs) of two groups, the MVI (n = 46) and non-MVI (n = 56) groups, using 16S ribosomal RNA gene sequencing data. At the operational taxonomic unit level, we employed random forest models to predict MVI risk and validated the results in independent validation cohorts [MVI group (n = 17) and non-MVI group (n = 15)].

Results

β diversity analysis, utilizing weighted UniFrac distances, revealed a significant difference between the MVI and non-MVI groups, as indicated by non-metric multidimensional scaling and principal coordinate analysis. We also observed a significant correlation between the characteristic intestinal microbial communities at the genus level and their main functions. Nine optimal microbial markers were identified, with an area under the curve of 79.76% between 46 MVI and 56 non-MVI samples and 79.80% in the independent verification group.

Conclusion

This pioneering analysis of the GM in patients with operable HBV-HCC with and without MVI opens new avenues for treating HBV-HCC with MVI. We successfully established a diagnostic model and independently verified microbial markers for patients with MVI. As preoperative targeted biomarkers, GM holds potential as a non-invasive tool for patients with HBV-HCC with MVI.

SUBMITTER: Peng YC

PROVIDER: S-EPMC10986448 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Specific gut microbiome signature predicts hepatitis B virus-related hepatocellular carcinoma patients with microvascular invasion.

Peng Yu-Chong YC Xu Jing-Xuan JX You Xue-Mei XM Huang Yi-Yue YY Ma Liang L Li Le-Qun LQ Qi Lu-Nan LN

Annals of medicine 20231219 2

<h4>Background</h4>We aimed to assess differences in intestinal microflora between patients with operable hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) with microvascular invasion (MVI) and those without MVI. Additionally, we investigated the potential of the microbiome as a non-invasive biomarker for patients with MVI.<h4>Methods</h4>We analyzed the preoperative gut microbiomes (GMs) of two groups, the MVI (<i>n</i> = 46) and non-MVI (<i>n</i> = 56) groups, using 16S ribosomal RN ...[more]

PMID: 38112540

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Project description:BackgroundWhether microvascular invasion is a prognosis factor for small hepatocellular carcinoma (sHCC) is controversial, and a preoperatively predictive model based on gadoxetate disodium (Gd-EOB-DTPA) MRI is clinically needed for MVI in sHCC.MethodsBetween March 2012 and September 2020, 455 consecutive patients with pathologically confirmed HCC ≤3 cm who underwent hepatectomy and preoperative Gd-EOB-DTPA MRI were retrospectively enrolled. Univariate and multivariate logistic regression combined with cox regression were conducted to find the confounding factors in the cohorts. Propensity score matching (PSM) was employed to balance the biases between MVI and non-MVI groups. Nomogram with C-index visualized the predictive model of MVI.ResultsMultivariate logistic regression identified that 5 characteristics (AFP, tumor size, tumor margin, peritumoral enhancement, radiologic capsule) were markedly associated with MVI of sHCC and incorporated into the nomogram with excellent predictive performance in the training (AUC/C-index: 0.884/0.874, n=288), validation (AUC/C-index: 0.845/0.828, n=123) and test cohorts (AUC/C-index: 0.903/0.954, n=44). Before PSM, histologic MVI independently affected tumor recurrence (hazard ratio: 1.555, 95% CI: 1.055-2.293, P=0.026). However, due to the confounder of tumor size, there was a significant bias between MVI-positive and MVI-negative groups (propensity score: 0.249±0.105 vs. 0.179±0.106, P<0.001). Meanwhile, the frequency of MVI significantly increased as tumor size growing (P<0.001). After PSM, 70 of 79 MVI cases matched with 171 non-MVI (total 332), and no biases were observed between the two groups (propensity score: 0.238±0.104 vs. 0.217±0.109, P=0.186). Although the median recurrence time in non-MVI sHCC was still longer than that in MVI group (74.3 vs. 43.0 months, P=0.063), MVI was not an independent risk factor for RFS in sHCC. Additionally, MVI was not independently vulnerable to mortality in our population.ConclusionsA preoperative model, mainly based on the peritumoral hallmarks of Gd-EOB-DTPA MRI, showed an excellent performance to predict the occurrence of MVI. Nevertheless, MVI was a potential but not an independent risk factor for recurrence and mortality in sHCC ≤3 cm.

Project description:In this study, a transcriptomic group classification based on a European population is tested on a Singapore cohort. The results highlight the genotype/phenotype correlation in a Southeast Asian population. The G1-G6 transcriptomic classification derived from hepatocellular carcinoma (HCC) resected from European patients, robustly reflected group-specific clinical/pathological features. We investigated the application of this molecular classification in Southeast Asian HCC patients.Gene expression analysis was carried out on HCC surgically resected in Singapore patients who were grouped into G1-G6 transcriptomic categories according to expression of 16 predictor genes (illustrated in Supplementary Table 1, http://links.lww.com/MD/B413 and Supplementary Fig. 1, http://links.lww.com/MD/B413) using quantitative reverse transcription polymerase chain reaction (RT-PCR). Univariate and multivariate polytomous logistic regression was used to investigate association between clinical variables and pooled transcriptomic classes G12, G3, and G456.HCC from Singapore (n?=?82) were distributed (%) into G1 (13.4), G2 (24.4), G3 (15.9), G4 (24.4), G5 (14.6), and G6 (7.3) subgroups. Compared to the European data, the Singapore samples were relatively enriched in G1-G3 versus G4-G6 tumors (53.7% vs 46.3%) reflecting the higher proportion of hepatitis B virus (HBV) patients in Singapore versus Europe samples (43% vs 30%). Pooled classes were defined as G12, G3, and G456. G12 was associated with higher alpha-fetoprotein (AFP) concentrations (OR?=?1.69, 95% CI: 1.30-2.20; P?<?0.0001) and G3 with microvascular invasion (OR?=?4.91, 95% CI: 1.06-24.8; P?=?0.047).The European and Singapore cohorts were generally similar relative to associations between transcriptomic groups and clinical features. This lends credence to the G1-G6 transcriptomic classifications being applicable regardless of the ethnic origin of HCC patients. The G3 group was associated with microvascular invasion and holds potential for investigation into the underlying mechanisms and selection for therapeutic clinical trials.

Project description:BackgroundThe association between gut microbiota and microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) remains unclarified. Hence, the microbiome analysis of patients with HCC might predict MVI development as an accurate, non-invasive, and convenient assessment. The aim of this study was to investigate the characteristics of gut microbiota in patients with HCC-MVI and establish a microbial prediction model of HCC-MVI based on a microbiome study.MethodsFecal samples were collected from 59 patients with HCC (24 of the total with MVI disease and 16 healthy controls) and were further analyzed by 16S rRNA amplicon sequencing followed by a comprehensive bioinformatic analysis. The diagnostic performance of microbiome characteristics in predicting MVI was assessed by receiver operating characteristic (ROC) curves. The correlation between gut microbiota and tumor microenvironment (TME) in the HCC-MVI group was further analyzed by using immunohistochemistry and immunofluorescence assay.ResultsA significant differentiation trend of microbiota composition and structure was observed between the HCC-MVI group and those without vascular invasion (HCC-NVI). Compared with HCC-NVI group and healthy controls, gut bacteria Klebsiella, Proteobacteria, Prevotellaceae, and Enterobacteriaceae were significantly enriched, whereas Firmicutes, Ruminococcus, and Monoglobaceae were significantly decreased in patients with HCC-MVI. Klebsiella was considered to be the key microbiome signature for patients with HCC-MVI. The area under the curve (AUC) of the established HCC-MVI microbial prediction model was 94.81% (95% CI: 87.63-100%). The percentage of M2-type tumor-associated macrophages (TAMs) was increased in the HCC-MVI group compared with the HCC-NVI group (p < 0.001). M2-type TAMs in TME were negatively correlated with Shannon and Simpson index of HCC-MVI gut microbiota (all p < 0.01). In addition, predicted KEGG pathways showed that the functional differences in the metabolic pathways of microbiota varied among the groups.ConclusionThe results indicated that differences existed in the fecal microbiome of patients with HCC-MVI and healthy controls. The prediction model of HCC-MVI established with certain gut bacterial signatures may have the potential to predict HCC-MVI outcome, and the characteristics of the fecal microbiome in patients with HCC may be associated with TME, though future larger-cohort studies are required to validate this supposition.

Project description:Background: Previous studies reported that stress-induced phosphoprotein 1 (STIP1) can be secreted by hepatocellular carcinoma (HCC) cells and is increased in the serum of HCC patients. However, the therapy-monitoring and prognostic value of serum STIP1 in HCC remains unclear. Here, we aimed to systemically explore the prognostic significance of serum STIP1 in HCC. Methods: A total of 340 HCC patients were recruited to this study; 161 underwent curative resection and 179 underwent transcatheter arterial chemoembolization (TACE). Serum STIP1 was detected by enzyme-linked immunosorbent assay (ELISA). Optimal cutoff values for serum STIP1 in resection and TACE groups were determined by receiver operating characteristic (ROC) analysis. Prognostic value was assessed by Kaplan-Meier, log-rank, and Cox regression analyses. Predictive values of STIP1 for objective response (OR) to TACE and MVI were evaluated by ROC curves and logistic regression. Results: Serum STIP1 was significantly increased in HCC patients when compared with chronic hepatitis B patients or health donors (both P < 0.05). Optimal cutoff values for STIP1 in resection and TACE groups were 83.43 and 112.06 ng/ml, respectively. High pretreatment STIP1 was identified as an independent prognosticator. Dynamic changes in high STIP1 status were significantly associated with long-term prognosis, regardless of treatment approaches. Moreover, post-TACE STIP1 was identified as an independent predictor for OR, with a higher area under ROC curve (AUC-ROC) than other clinicopathological features. Specifically, pretreatment STIP1 was significantly increased in patients with microvascular invasion (MVI), and was confirmed as a novel, powerful predictor for MVI. Conclusions: Serum STIP1 is a promising biomarker for outcome evaluation, therapeutic response assessment, and MVI prediction in HCC. Integration serum STIP1 detection into HCC management might facilitate early clinical decision making to improve the prognosis of HCC.

Dataset Information

Specific gut microbiome signature predicts hepatitis B virus-related hepatocellular carcinoma patients with microvascular invasion.

Background

Methods

Results

Conclusion

Publications

Specific gut microbiome signature predicts hepatitis B virus-related hepatocellular carcinoma patients with microvascular invasion.

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