1.Availability and use of child safety seats among children aged 0-3 years
CHEN Bo ; WANG Xihui ; QIU Fengqian ; YU Yan ; GAO Shuna ; HE Lihua ; LI Weiyi ; JI Yunfang ; CHEN Weihua
Journal of Preventive Medicine 2025;37(1):21-25
Objective:
To investigate the availability and use of child safety seats among children aged 0-3 years, so as to provide the basis for improving riding safety for children.
Methods:
Parents of children aged 0-3 years in Huangpu District, Shanghai Municipality, were recruited using the stratified multistage random sampling method from May to July 2024. Demographic information, family travel patterns, the use of child safety seat and related health beliefs were collected using questionnaire surveys. Factors affecting the use of child safety seats were identified using a multivariable logistic regression model.
Results:
Totally 514 valid questionnaires were recovered, with an effective rate of 96.98%. The respondents included 122 fathers (23.74%) and 392 mothers (76.26%), with a median age of 34.00 (interquartile range, 5.00) years. There were 446 families equipping with child safety seats, accounting for 86.77%; and 169 families using child safety seats, accounting for 32.88%. Multivariable logistic regression analysis showed that the parents who had children aged >1-2 years (OR=0.597, 95%CI: 0.366-0.973), travelled 2-4 times per month (OR=0.359, 95%CI: 0.213-0.607) or once per month or less (OR=0.384, 95%CI: 0.202-0.729), and scored high in perceived barrier (OR=0.634, 95%CI: 0.486-0.827) were less likely to use child safety seats; the parents who had children with local household registration (OR=2.506, 95%CI: 1.356-4.633), travelled 5-<10 km (OR=1.887, 95%CI: 1.148-3.101) or ≥10 km (OR=2.319, 95%CI: 1.355-3.967), always wore seat belts (OR=2.342, 95%CI: 1.212-4.524), scored high in perceived susceptibility (OR=1.392, 95%CI: 1.091-1.778) and self-efficacy (OR=1.413, 95%CI: 1.156-1.727) were more likely to use child safety seats.
Conclusions
Equipping family cars with child safety seats and using them can prevent and reduce traffic injuries among children aged 0-3 years. It is recommended to strengthen publicity to promote the use of child safety seats.
2.Long-Term Real-World Outcomes of Tenofovir Alafenamide in Chronic Hepatitis B: Detailed Analysis of Treatment-Naive and Experienced Patients
Yu-Xuan SONG ; Guang-Jun SONG ; Hui MA ; Bo FENG ; Yan-Di XIE
The Korean Journal of Gastroenterology 2025;85(1):64-72
Background/Aims:
This study assessed the long-term efficacy and safety of tenofovir alafenamide (TAF) in real-world settings.
Methods:
Patients who were candidates for TAF treatment and were followed up at 12-week intervals over 192 weeks were enrolled in this study.
Results:
One hundred and forty-four patients (50 treatment-naive and 94 treatment-experienced) were included in this study. The cumulative incidence rates of cirrhosis and hepatocellular carcinoma at 192 weeks were 3.9% and 0.7%, respectively. In treatment-naive patients, the rates of a virological response, HBeAg conversion, and HBsAg loss at 192 weeks were 100%, 33.3%, and 2%, respectively. The treatment-naive patients exhibited higher baseline HBsAg levels than the treatment-experienced patients (4.31 log10IU/mL vs. 3.97 log10IU/mL). A significant decrease in the HBsAg levels from the baseline was observed at 144 and 192 weeks in the treatment-naive patients (p=0.01). The baseline body mass index (BMI) <25 kg/m2 (p=0.02) and HBsAg <3.3 log10IU/mL (p=0.04) were identified as predictive factors for a decrease in HBsAg ≥0.5 log10IU/mL at 48 weeks. The eGFR levels were consistently lower in the treatment-experienced patients throughout the study. Although the treatment-naive patients showed no abnormal increases in urinary URBP, the treatment-experienced patients showed elevated urinary β2MG and NAG levels at the baseline, which decreased over the treatment course. The total cholesterol, triglyceride, and low-density lipoprotein levels were similar in both groups.
Conclusions
Prolonging the TAF treatment duration enhances the virological response rate. The decline in HBsAg levels was more significant in the treatment-naive patients than in the treatment-experienced patients. The baseline BMI <25 kg/m2 and HBsAg <3.3 log10IU/mL were predictive factors for a significant decline in HBsAg at 48 weeks. TAF has high renal safety and no significant impact on lipid levels.
3.Better Chemotherapeutic Response of Small Cell Lung Cancer in Never Smokers than in Smokers
Ha-Young PARK ; Hyung-Joo OH ; Hwa Kyung PARK ; Joon-Young YOON ; Chang-Seok YOON ; Bo Gun KHO ; Tae-Ok KIM ; Hong-Joon SHIN ; Chul-Kyu PARK ; Yong-Soo KWON ; Yu-Il KIM ; Sung-Chul LIM ; Young-Chul KIM ; In-Jae OH
Tuberculosis and Respiratory Diseases 2025;88(2):334-341
Background:
Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC.
Methods:
We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021.
Results:
Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers.
Conclusion
In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.
4.Shaoyaotang Containing Serum Mediates Fas/FasL Pathway to Inhibit Lipopolysaccharide Induced Inflammation and Apoptosis of Caco-2 Cells
Yuting YANG ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Nianjia XIE ; Bo ZOU ; Daguang CHEN ; Erle LIU ; Yi LU ; Zhaowen LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):62-69
ObjectiveTo investigate the effects of different concentrations of Shaoyaotang-containing serum on lipopolysaccharide (LPS)-induced inflammation of human colorectal adenocarcinoma (Caco-2) cells by inhibiting apoptosis via activating the tumor necrosis factor (TNF) receptor superfamily member 6 (Fas)/Fas ligand (FasL) pathway. MethodsCaco-2 cells were allocated into blank, model (LPS, 10 mg·L-1), Shaoyaotang-containing serum (5%, 10%, 15%, 20%), and Fas inhibitor (KR-33493, 20 mmol·L-1) groups. Except the blank group, the other groups were stimulated with 10 mg·L-1 LPS for 24 h for the modeling of inflammation. After successful modeling, the blank, Fas inhibitor, and model groups were treated with blank serum, and the Shaoyaotang-containing serum groups were treated with the serum samples at corresponding concentrations for 24 h. The Fas inhibitor group was subjected to KR-33493 pretreatment for 1 h. Cell proliferation and viability were examined by the cell-counting kit-8 (CCK-8) method. The levels of interleukin (IL)-6, IL-1β, and TNF-α were measured by enzyme-linked immunosorbent assay. Apoptosis was detected by flow cytometry. The protein and mRNA levels of Fas, FasL, cysteinyl aspartate-specific proteinase (Caspase)-3, Caspase-9, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), respectively. ResultsCompared with the blank group, the model group presented a decrease in cell survival rate (P<0.01). Compared with that in the model group, the cell survival rate showed no significant change in the 5% Shaoyaotang-containing serum group but increased in the 10%, 15%, and 20% Shaoyaotang-containing serum groups (P<0.01). Since there was no statistical difference between the 5% Shaoyaotang-containing serum group and the model group, 10%, 15%, and 20% Shaoyaotang-containing sera were selected for the follow-up study. Compared with the blank group, the model group showed risen levels of IL-6, IL-1β, and TNF-α (P<0.01), an increased apoptosis rate (P<0.01), up-regulated protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.01), and down-regulated protein and mRNA levels of Bcl-2 (P<0.01). Compared with the model group, the Fas inhibitor group and the 10%, 15%, and 20% Shaoyaotang-containing serum groups showed declined levels of IL-6, IL-1β, and TNF-α (P<0.01), decreased apoptosis rates (P<0.01), down-regulated protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.05, P<0.01), and up-regulated protein and mRNA levels of Bcl-2 (P<0.05, P<0.01). In addition, the 15% and 20% Shaoyaotang-containing serum groups had lower levels of IL-6, IL-1β, and TNF-α (P<0.05, P<0.01), lower apoptosis rates (P<0.05, P<0.01), lower protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.05, P<0.01), and higher protein and mRNA levels of Bcl-2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can reduce the content of inflammatory factors in Caco-2 cells, down-regulate the protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax, and up-regulate the protein and mRNA levels of Bcl-2 under the intervention of LPS by regulating the Fas/FasL pathway and inhibiting the apoptosis of intestinal epithelial cells in ulcerative colitis.
5.Shaoyaotang Alleviates Damage of Tight Junction Proteins in Caco-2 Cell Model of Inflammation by Regulating RhoA/ROCK Pathway
Nianjia XIE ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Yuting YANG ; Bo ZOU ; Da ZHAO ; Yi LU ; Mingsheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):70-77
ObjectiveTo investigate the protective effect and mechanism of Shaoyaotang (SYD) on the lipopolysaccharide (LPS)-induced damage of tight junction proteins in the human colorectal adenocarcinoma (Caco-2) cell model of inflammation via the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) pathway. MethodsCaco-2 cells were grouped as follows: Blank, model (LPS, 10 mg·L-1), SYD-containing serum (10%, 15%, and 20%), and inhibitor (Fasudil, 25 μmol·L-1). After 24 hours of intervention, the cell viability in each group was examined by the cell-counting kit 8 (CCK-8) method. Enzyme-linked immunosorbent assay was employed to determine the levels of endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of RhoA, ROCK2, claudin-5, and zonula occludens-1 (ZO-1) in cells of each group. ResultsCompared with the blank group, the model group showcased a marked reduction in the cell viability (P<0.01), elevations in the levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), declines in both mRNA and protein levels of ZO-1 and claudin-5 (P<0.01), and rises in mRNA and protein levels of RhoA and ROCK2 (P<0.01). Compared with the model group, the Shaoyaotang-containing serum (10%, 15%, and 20%) groups had enhanced cell viability (P<0.01), lowered levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), up-regulated mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and down-regulated mRNA and protein levels of RhoA and ROCK2 (P<0.01). Moreover, the inhibitor group and the 15% and 20% Shaoyaotang-containing serum groups had lower levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), higher mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and lower mRNA and protein levels of RhoA and ROCK2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can lower the levels of LPS-induced increases in levels of inflammatory cytokines and endothelin to ameliorate the damage of tight junction proteins of the Caco-2 cell model of inflammation by regulating the expression of proteins in the RhoA/ROCK pathway.
6.Shaoyaotang Containing Serum Mediates Fas/FasL Pathway to Inhibit Lipopolysaccharide Induced Inflammation and Apoptosis of Caco-2 Cells
Yuting YANG ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Nianjia XIE ; Bo ZOU ; Daguang CHEN ; Erle LIU ; Yi LU ; Zhaowen LYU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):62-69
ObjectiveTo investigate the effects of different concentrations of Shaoyaotang-containing serum on lipopolysaccharide (LPS)-induced inflammation of human colorectal adenocarcinoma (Caco-2) cells by inhibiting apoptosis via activating the tumor necrosis factor (TNF) receptor superfamily member 6 (Fas)/Fas ligand (FasL) pathway. MethodsCaco-2 cells were allocated into blank, model (LPS, 10 mg·L-1), Shaoyaotang-containing serum (5%, 10%, 15%, 20%), and Fas inhibitor (KR-33493, 20 mmol·L-1) groups. Except the blank group, the other groups were stimulated with 10 mg·L-1 LPS for 24 h for the modeling of inflammation. After successful modeling, the blank, Fas inhibitor, and model groups were treated with blank serum, and the Shaoyaotang-containing serum groups were treated with the serum samples at corresponding concentrations for 24 h. The Fas inhibitor group was subjected to KR-33493 pretreatment for 1 h. Cell proliferation and viability were examined by the cell-counting kit-8 (CCK-8) method. The levels of interleukin (IL)-6, IL-1β, and TNF-α were measured by enzyme-linked immunosorbent assay. Apoptosis was detected by flow cytometry. The protein and mRNA levels of Fas, FasL, cysteinyl aspartate-specific proteinase (Caspase)-3, Caspase-9, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), respectively. ResultsCompared with the blank group, the model group presented a decrease in cell survival rate (P<0.01). Compared with that in the model group, the cell survival rate showed no significant change in the 5% Shaoyaotang-containing serum group but increased in the 10%, 15%, and 20% Shaoyaotang-containing serum groups (P<0.01). Since there was no statistical difference between the 5% Shaoyaotang-containing serum group and the model group, 10%, 15%, and 20% Shaoyaotang-containing sera were selected for the follow-up study. Compared with the blank group, the model group showed risen levels of IL-6, IL-1β, and TNF-α (P<0.01), an increased apoptosis rate (P<0.01), up-regulated protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.01), and down-regulated protein and mRNA levels of Bcl-2 (P<0.01). Compared with the model group, the Fas inhibitor group and the 10%, 15%, and 20% Shaoyaotang-containing serum groups showed declined levels of IL-6, IL-1β, and TNF-α (P<0.01), decreased apoptosis rates (P<0.01), down-regulated protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.05, P<0.01), and up-regulated protein and mRNA levels of Bcl-2 (P<0.05, P<0.01). In addition, the 15% and 20% Shaoyaotang-containing serum groups had lower levels of IL-6, IL-1β, and TNF-α (P<0.05, P<0.01), lower apoptosis rates (P<0.05, P<0.01), lower protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax (P<0.05, P<0.01), and higher protein and mRNA levels of Bcl-2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can reduce the content of inflammatory factors in Caco-2 cells, down-regulate the protein and mRNA levels of Fas, FasL, Caspase-3, Caspase-9, and Bax, and up-regulate the protein and mRNA levels of Bcl-2 under the intervention of LPS by regulating the Fas/FasL pathway and inhibiting the apoptosis of intestinal epithelial cells in ulcerative colitis.
7.Shaoyaotang Alleviates Damage of Tight Junction Proteins in Caco-2 Cell Model of Inflammation by Regulating RhoA/ROCK Pathway
Nianjia XIE ; Dongsheng WU ; Hui CAO ; Yu ZHANG ; Yuting YANG ; Bo ZOU ; Da ZHAO ; Yi LU ; Mingsheng WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):70-77
ObjectiveTo investigate the protective effect and mechanism of Shaoyaotang (SYD) on the lipopolysaccharide (LPS)-induced damage of tight junction proteins in the human colorectal adenocarcinoma (Caco-2) cell model of inflammation via the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) pathway. MethodsCaco-2 cells were grouped as follows: Blank, model (LPS, 10 mg·L-1), SYD-containing serum (10%, 15%, and 20%), and inhibitor (Fasudil, 25 μmol·L-1). After 24 hours of intervention, the cell viability in each group was examined by the cell-counting kit 8 (CCK-8) method. Enzyme-linked immunosorbent assay was employed to determine the levels of endothelin-1 (ET-1), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of RhoA, ROCK2, claudin-5, and zonula occludens-1 (ZO-1) in cells of each group. ResultsCompared with the blank group, the model group showcased a marked reduction in the cell viability (P<0.01), elevations in the levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), declines in both mRNA and protein levels of ZO-1 and claudin-5 (P<0.01), and rises in mRNA and protein levels of RhoA and ROCK2 (P<0.01). Compared with the model group, the Shaoyaotang-containing serum (10%, 15%, and 20%) groups had enhanced cell viability (P<0.01), lowered levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.01), up-regulated mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and down-regulated mRNA and protein levels of RhoA and ROCK2 (P<0.01). Moreover, the inhibitor group and the 15% and 20% Shaoyaotang-containing serum groups had lower levels of ET-1, TNF-α, IL-1β, and IL-6 (P<0.05, P<0.01), higher mRNA and protein levels of ZO-1 and claudin-5 (P<0.05, P<0.01), and lower mRNA and protein levels of RhoA and ROCK2 (P<0.05, P<0.01) than the 10% Shaoyaotang-containing serum group. ConclusionThe Shaoyaotang-containing serum can lower the levels of LPS-induced increases in levels of inflammatory cytokines and endothelin to ameliorate the damage of tight junction proteins of the Caco-2 cell model of inflammation by regulating the expression of proteins in the RhoA/ROCK pathway.
8.Comparing haploidentical transplantation with post‑transplantation cyclophosphamide and umbilical cord blood transplantation using targeted busulfan in children and adolescents with hematologic malignancies
Kyung Taek HONG ; Bo Kyung KIM ; Hong Yul AN ; Jung Yoon CHOI ; Sang Hoon SONG ; Kyung‑Sang YU ; In‑Jin JANG ; Hyoung Jin KANG
Blood Research 2025;60():7-
Purpose:
This study compared the outcomes of haploidentical-related donor (HRD) and umbilical cord blood (UCB) hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematologic malignancies.
Methods:
Data on patients who underwent HRD HSCT with post-transplant cyclophosphamide (n = 41) and UCB HSCT (n = 24) after targeted busulfan-based myeloablative conditioning with intensive pharmacokinetic monitoring between 2009 and 2018 were retrospectively analyzed.
Results:
The median follow-up durations in the HRD and UCB groups were 7.0 and 10.9 years, respectively. The cumu‑ lative incidence of acute graft-versus-host disease (GVHD) grades II–IV and moderate-to-severe chronic GVHD did not differ significantly between the groups. However, the HRD group demonstrated significantly lower rates of acute GVHD grades III–IV (4.9% vs. 29.2%, p = 0.009) and non-relapse mortality (2.6% vs. 34.2%, p < 0.001) but a higher relapse incidence (32.1% vs. 8.8%, p = 0.004) than the UCB group. The 5-year event-free and overall survival rates were 65.8% and 54.2% (p = 0.204) and 78.0% and 65.7% (p = 0.142) for the HRD and UCB groups, respectively. Multivariate analysis identified disease status as a significant risk factor for overall survival (hazard ratio, 3.24; p = 0.016). Additionally, UCB HSCT exhibited a trend toward worse event-free survival compared to HRD HSCT (hazard ratio, 2.63; p = 0.05).
Conclusions
These findings indicate that HRD HSCT with post-transplant cyclophosphamide provides promising outcomes compared to UCB HSCT in pediatric patients, with a trend toward improved survival over a long-term follow-up period exceeding a median of 7 years. Thus, HRD HSCT may be a valuable option for pediatric patients with‑ out human leukocyte antigen-matched donors.
9.Frequent association of malignant effusions in plasmablastic lymphoma:a single‑institutional experience of nine cases in Taiwan
Bo‑Jung CHEN ; Yu‑Ting KUO ; Sheng‑Tsung CHANG ; Khin‑Than WIN ; Shang‑Wen CHEN ; Sheng‑Yen HSIAO ; Yin‑Hsun FENG ; Yen‑Chuan HSIEH ; Shih‑Sung CHUANG
Blood Research 2025;60():22-
Purpose:
Plasmablastic lymphoma (PBL) is a rare, aggressive lymphoma that is characterized by terminal B-cell differ‑ entiation. In the West, PBL usually occurs in patients with immunodeficiencies, particularly those induced by human immunodeficiency virus (HIV) infection. We investigated the clinicopathological features of PBL at a single institute in Taiwan, where HIV infection is rare.
Methods:
This retrospective chart review identified PBL cases that were treated at a single institute in southern Tai‑ wan between 2008 and 2024.
Results:
We identified nine patients (four males and five females; median age 71 years). Of the eight patients tested for HIV, only one tested positive. Pathologically, the tumors showed plasmablastic morphology and immunopheno‑ type, and three (33%) cases tested positive for Epstein–Barr virus. Six (67%) patients presented with Stage IV disease, including five (56%) with malignant effusion. Six patients were treated with chemotherapy and the remaining three received only supportive care. During a median follow-up of 10 months, five patients died of progressive disease, two died of unrelated diseases, and two were alive with PBL relapse.
Conclusion
In Taiwan, PBL constitutes a rare and aggressive clinical condition and is frequently associated with malignant effusion. In contrast to Western patients, the PBL in most patients from Taiwan was unrelated to HIV infection.
10.Integrated molecular characterization of sarcomatoid hepatocellular carcinoma
Rong-Qi SUN ; Yu-Hang YE ; Ye XU ; Bo WANG ; Si-Yuan PAN ; Ning LI ; Long CHEN ; Jing-Yue PAN ; Zhi-Qiang HU ; Jia FAN ; Zheng-Jun ZHOU ; Jian ZHOU ; Cheng-Li SONG ; Shao-Lai ZHOU
Clinical and Molecular Hepatology 2025;31(2):426-444
Background:
s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated.
Methods:
In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs.
Results:
Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment.
Conclusions
We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.


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