Outcomes of endoscopic submucosal dissection versus esophagectomy for poorly differentiated superficial esophageal squamous cell carcinoma: A 10-year cohort study.

BACKGROUNDS: The efficacy of endoscopic submucosal dissection (ESD) to treat poorly differentiated superficial esophageal squamous cell carcinoma (SESCC) is unclear. AIMS: To exploring the efficacy and prognosis of ESD treatment poorly differentiated SESCC compared with esophagectomy. METHODS: A retrospective cohort study was conducted, the data of poorly differentiated SESCC patients who received ESD or esophagectomy from Jan 2011 to Jan 2021 were analyzed. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and procedure-related variables were compared between ESD and esophagectomy group. RESULTS: 95 patients underwent ESD, while 86 underwent esophagectomy. No significant differences were found between the two groups in OS (P = 0.587), DSS (P = 0.172), and RFS (P = 0.111). Oncologic outcomes were also similar between the two groups in propensity score-matched analysis. For T1a ESCC, the rates of R0 resection, LVI or nodal metastasis and additional therapy were similar between ESD and esophagectomy groups. But for T1b ESCC, the rates of positive resection margin and additional therapy were significantly higher in ESD group than those in esophagectomy group. CONCLUSIONS: ESD is a minimally invasive procedure that has comparable oncologic outcomes with esophagectomy for treatment poorly differentiated T1a ESCC. However, ESD is not suitable for poorly differentiated T1b ESCC, additional surgery or radiochemotherapy should be required.

HPLC with chiral stationary phase for separation and kinetics study of aspartic acid epimerization in Peroxiredoxin 2 active site peptide.

Amino acid epimerization, a process of converting L-amino acids to D-amino acids, will lead to modification in the protein structure and, subsequently, its biological function. This modification causes no change in protein m/z and may be overlooked during protein analysis. Aspartic Acid Epimerization (AAE) is faster than other amino acids and could be accelerated by free radicals and peroxides. In this work, a novel and site-specific HPLC method using a chiral stationary phase for determining the AAE in the active site model peptide (AP) of Peroxiredoxin 2 has been developed and validated. The developed method showed good linearity (1 - 200 µg/mL) and recoveries of the limit of quantification (LOQ), low, medium, and high concentrations were between 85% and 115%. The Kinetics of AAE in AP were studied using the developed method, and the results showed that when ascorbic acid and Cu2+ coexisted, the AP epimerized rapidly. The AAE extent increased with time and was positively correlated with hydrogen peroxide generation.

Enhancing Stability and Antioxidant Activity of Resveratrol-Loaded Emulsions by Ovalbumin-Dextran Conjugates.

A reliable strategy for improving the stability and shelf life of protein-stabilized systems is by covalently attaching the protein onto a polysaccharide. In this study, ovalbumin (OVA) was modified with dextran (DEX) of different molecular weights by the Maillard reaction, and was used to enhance the stability of emulsions loaded with resveratrol. The surface hydrophobicity, thermal stability, and FT-IR spectroscopy of the OVA-DEX conjugates were evaluated. The results showed that the surface hydrophobicity of OVA decreased, while the thermal stability of OVA was significantly improved after DEX covalent modification. The OVA-DEX1k-stabilized emulsion exhibited high encapsulation efficiency of resveratrol, with the value of 89.0%. In addition, OVA-DEX was considerably more effective in droplet stabilization against different environmental stresses (heat, pH, and ionic strength). After 28 days of storage at 25 °C, the OVA-stabilized emulsion showed faster decomposition of resveratrol, whereas the OVA-DEX-conjugate-stabilized emulsion had approximately 73% retention of resveratrol. Moreover, the antioxidant activity of resveratrol-loaded emulsions stabilized by OVA-DEX was higher during storage under different temperatures. These results proved that the OVA-DEX conjugates had the potential to form stable, food-grade emulsion-based delivery systems against environmental stresses, which strongly supports their potential in the field of food and biomedical applications.

A multifunctional dual cation doping strategy to stabilize high-voltage medium-nickel low-cobalt lithium layered oxide cathode.

High-voltage medium-nickel low-cobalt lithium layered oxide cathode materials are intriguing for lithium-ion batteries (LIBs) applications because of their relatively low cost and high capacity. Unfortunately, high charging voltage induces bulk layered structure decline and interface environment deterioration, low cobalt content reduces lithium diffusion kinetics, severely limiting the performance liberation of this kind of cathode. Here, a multifunctional Al/Zr dual cation doping strategy is employed to enhance the electrochemical performance of LiNi0.6Co0.05Mn0.35O2 (NCM) cathode at a high charging cut-off voltage of 4.5 V. On the one hand, Al/Zr co-doping weakens the Li+/Ni2+ mixing through magnetic interactions due to the inexistence of unpaired electrons for Al3+ and Zr4+, thereby increasing the lithium diffusion rate and suppressing the harmful coexistence of H1 and H2 phases. On the other hand, they enhance the lattice oxygen framework stability due to strong Al-O and Zr-O bonds, inhibiting the undesired H2 to H3 phase transition and interface lattice oxygen loss, thereby enhancing the stability of the bulk structure and cathode-electrolyte interface. As a result, Al/Zr co-doped NCM (NCMAZ) shows a 94.2 % capacity retention rate after 100 cycles, while that of NCM is only 79.4 %. NCMAZ also exhibits better rate performance than NCM, with output capacities of 92 mAh/g and 59 mAh/g at a high current density of 5C, respectively. The modification strategy will make the high-voltage medium-nickel low-cobalt cathode closer to practical applications.

Exploring the mechanism of LncRNA CASC15 affecting hepatocellular carcinoma through miRNA.

This study aimed to determine the potential mechanisms through which long noncoding (Lnc) RNA cancer susceptibility candidate 15 (CASC15) affects hepatocellular carcinoma (HCC). We retrieved HCC RNA-seq and clinical information from the UCSC Xena database. The differential expression (DE) of CASC15 was detected. Overall survival was analyzed using Kaplan-Meier (K-M) curves. Molecular function and signaling pathways affected by CASC15 were determined using Gene Set Enrichment Analysis. Associations between CASC15 and the HCC microenvironment were investigated using immuno-infiltration assays. A differential CASC15-miRNA-mRNA network and HCC-specific CASC15-miRNA-mRNA ceRNA network were constructed. The overexpression of CASC15 in HCC tissues was associated with histological grade, clinical stage, pathological T stage, poor survival, more complex immune cell components, and 12 immune checkpoints. We identified 27 DE miRNAs and 270 DE mRNAs in the differential CASC15-miRNA-mRNA network, and 10 key genes that were enriched in 12 cancer-related signaling pathways. Extraction of the HCC-specific CASC15-miRNA-mRNA network revealed that IGF1R, MET, and KRAS were associated with HCC progression and occurrence. Our bioinformatic findings confirmed that CASC15 is a promising prognostic biomarker for HCC, and elevated levels in HCC are associated with the tumor microenvironment. We also constructed a disease-specific CASC15-miRNA-mRNA regulatory ceRNA network that provides a new perspective for the precise indexing of patients with elevated levels of CASC15.

Single-Cell Characterization of the Tumor Ecosystem in Liver Cancer.

Tumor heterogeneity along with the complex landscape of the tumor microenvironment create critical challenges for effective liver cancer interventions. Characterizing the tumor ecosystem at the single-cell level may provide insight into the collective behaviors of tumor cells and their interplays with stromal and immune cells. Here we introduce the experimental protocol and computational methods for the single-cell study of liver cancer, which may be essential for a mechanistic understanding of the tumor ecosystem in liver cancer and further pave the way for developing novel therapeutics.

Clinical Features and Influencing Factors of Acute Kidney Injury in Patients with Intestinal Obstruction: A Meta-Analysis.

Background: Intestinal obstruction frequently leads to acute kidney injury (AKI), yet understanding the specific clinical features and influencing factors in these patients remains limited. Objective: This study aims to comprehensively evaluate the clinical features and affecting factors of AKI in patients with intestinal obstruction. Methods: We conducted a systematic search of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service platform, VIP, and China Biology Medicine Literature Database from 2010 to the present. Relevant literature addressing the clinical features or affecting factors of AKI in patients with intestinal obstruction was retrieved. The study group (SG) comprised patients with intestinal obstruction complicated by AKI, while the control group (CG) included patients without AKI after intestinal obstruction. Meta-analysis was performed to investigate the clinical features of both patient groups and funnel plots were employed to assess publication bias. Results: This study included 5 articles with a total of 7583 patients (1472 in the SG and 6111 in the CG). Meta-analysis results indicated a higher prevalence of hypertension (OR=1.80, 95% CI: 1.59-2.04, P < .00001), cardiovascular disease (OR=1.60, 95% CI: 1.06-2.41, P = .03), and diabetes (OR=1.61, 95% CI: 1.35-1.91, P < .00001) in both groups. Additionally, factors such as infection rate (OR=4.03, 95% CI: 2.10-7.73, P < .0001), age (OR=2.90, 95% CI: 1.07-7.90, P = .04), and BMI (OR=1.31, 95% CI: 1.15-1.48, P < .0001) significantly influenced AKI occurrence. No significant difference was observed in the history of pelvic surgery between both groups (OR=0.91, 95% CI: 0.53-1.55, P = .73). Funnel plot analysis suggested minimal publication bias. Conclusions: Age, BMI, hypertension, cardiovascular disease, diabetes mellitus, and infection emerge as primary influencing factors for AKI in patients with intestinal obstruction. Our findings advocate for early interventions to mitigate the global incidence of AKI in this patient population.

Lineage and ecology define liver tumor evolution in response to treatment.

A tumor ecosystem constantly evolves over time in the face of immune predation or therapeutic intervention, resulting in treatment failure and tumor progression. Here, we present a single-cell transcriptome-based strategy to determine the evolution of longitudinal tumor biopsies from liver cancer patients by measuring cellular lineage and ecology. We construct a lineage and ecological score as joint dynamics of tumor cells and their microenvironments. Tumors may be classified into four main states in the lineage-ecological space, which are associated with clinical outcomes. Analysis of longitudinal samples reveals the evolutionary trajectory of tumors in response to treatment. We validate the lineage-ecology-based scoring system in predicting clinical outcomes using bulk transcriptomic data of additional cohorts of 716 liver cancer patients. Our study provides a framework for monitoring tumor evolution in response to therapeutic intervention.

Vaginal reconstruction by collagen scaffolds loaded with vaginal epithelial and smooth muscle cells in pigs.

In women, a healthy and functional vagina is important for the maintenance of a good quality of life. Various factors, including congenital anomalies, cancer, trauma, infections, inflammation, or iatrogenic injuries, can lead to damage or loss of the vaginal structure, necessitating repair or replacement. Often, such reconstruction procedures involve the use of nonvaginal tissue substitutes, like segments of the large intestine or skin, which are less than ideal both anatomically and functionally. Therefore, there is an urgent need to develop new methods of vaginal reconstruction. In this study, we established a new method for isolation and expansion of vaginal epithelial and smooth muscle cells. Subsequently, collagen scaffolds designed for vaginal reconstruction were loaded with vaginal epithelial and smooth muscle cells in vitro and tested in vivo using the vaginal excision pig model. The results showed that the collagen scaffold loaded with vaginal epithelial and smooth muscle cells significantly promotes the reconstruction of the vagina compared with small intestinal submucosa (SIS) membrane or bare collagen scaffold. Notably, the reconstructed vaginal tissues exhibit remarkable similarity to their normal counterparts, encompassing not only the vaginal epithelium and smooth muscle but also the intricate networks of blood vessels and nerves. These compelling results underscore the feasibility of a tissue engineering approach in vaginal reconstruction, offering promising prospects for improving the quality of life in affected individuals.

The value of an MRI-based radiomics model in predicting the survival and prognosis of patients with extrahepatic cholangiocarcinoma.

OBJECTIVES: The study aimed to establish radiomics models based on magnetic resonance imaging (MRI) multiparameter images to predict the survival and prognosis of patients with extrahepatic cholangiocarcinoma (ECC). METHODS: Seventy-eight patients with ECC confirmed by pathology were collected retrospectively. The radiomics model_a/b/c were constructed based on the 1/2/3-year survival of patients with ECC. The best texture features were selected according to postoperative survival time and ECC patient status to calculate the radiomics score (Rad-score). A cutoff value was selected, and patients were divided into high-risk and low-risk groups. RESULTS: Model_a, model_b, and model_c were used to predict 1-, 2-, and 3-year postoperative survival rates, respectively. The area under the curve values in the training and test groups were 1.000 and 0.933 for model_a, 0.909 and 0.907 for model_b, 1.000 and 0.975 for model_c, respectively. The survival prediction model based on the Rad-score showed that the postoperative mortality risk differed significantly between risk groups (p < 0.0001). CONCLUSIONS: The MRI radiomics model could be used to predict the survival and prognosis of patients with ECC.

Survival analysis of patients with extrahepatic cholangiocarcinoma: a nomogram for clinical and MRI features.

BACKGROUND: This study aimed to establish a predictive model to estimate the postoperative prognosis of patients with extrahepatic cholangiocarcinoma (ECC) based on preoperative clinical and MRI features. METHODS: A total of 104 patients with ECC confirmed by surgery and pathology were enrolled from January 2013 to July 2021, whose preoperative clinical, laboratory, and MRI data were retrospectively collected and examined, and the effects of clinical and imaging characteristics on overall survival (OS) were analyzed by constructing Cox proportional hazard regression models. A nomogram was constructed to predict OS, and calibration curves and time-dependent receiver operating characteristic (ROC) curves were employed to assess OS accuracy. RESULTS: Multivariate regression analyses revealed that gender, DBIL, ALT, GGT, tumor size, lesion's position, the signal intensity ratio of liver to paraspinal muscle (SIRLiver/Muscle), and the signal intensity ratio of spleen to paraspinal muscle (SIRSpleen/Muscle) on T2WI sequences were significantly associated with OS, and these variables were included in a nomogram. The concordance index of nomogram for predicting OS was 0.766, and the AUC values of the nomogram predicting 1-year and 2-year OS rates were 0.838 and 0.863, respectively. The calibration curve demonstrated good agreement between predicted and observed OS. 5-fold and 10-fold cross-validation show good stability of nomogram predictions. CONCLUSIONS: Our nomogram based on clinical, laboratory, and MRI features well predicted OS of ECC patients, and could be considered as a convenient and personalized prediction tool for clinicians to make decisions.

Long-term survival of stage Ib lung adenocarcinoma with postoperative brain oligometastasis: a case report and literature review.

Lung adenocarcinoma remains one of the most frequent and deadly tumour entities. Early-stage lung adenocarcinoma is extremely difficult to detect and is also easy to recur or metastasize after treatment. Since the new adenocarcinoma classification was presented in 2011, several studies have shown that patients with solid and/or micropapillary (S/MP) predominant patterns showed a worse prognosis. Here we report the case of a 54-year-old woman who was diagnosed with stage Ib lung adenocarcinoma with S/MP components and developed an isolated brain oligometastasis after resection and adjuvant therapy. A craniocerebral operation was performed, combined with radiotherapy and targeted therapy, and the patient eventually achieved a good quality of life. Our work reviews the clinical features of lung cancer complicated with S/MP components, the relationship between MP and epidermal growth factor receptor (EGFR) mutation, as well as treatment strategies for such a patient with postoperative brain oligometastasis of lung adenocarcinoma complicated with EGFR Exon19del mutation.

The trend of allogeneic tendon decellularization: literature review.

Tendon injuries repair is a significant burden for orthopaedic surgeons. Finding a proper graft material to repair tendon is one of the main challenges in orthopaedics, for which the requirement of substitute for tendon repair would be different for each clinical application. Among biological scaffolds, the use of decellularized tendon increasingly represents an interesting approach to treat tendon injuries and several articles have investigated the approaches of tendon decellularization. To understand the outcomes of the the approaches of tendon decellularization on effect of tendon transplantation, a literature review was performed. This review was conducted by searching in Pubmed and Embase and 64 studies were included in this study. The findings revealed that the common approaches to decellularize tendon include chemical, physical, and enzymatic decellularization methods or their combination. With the development of tissue engineering, researchers also put forward new theories such as automatic acellular machine, 3D printing technology to manufacture acellular scaffold.

1,2,4-Triazole benzamide derivative TPB against Gaeumannomyces graminis var. tritici as a novel dual-target fungicide inhibiting ergosterol synthesis and adenine nucleotide transferase function.

BACKGROUND: Isopropyl 4-(2-chloro-6-(1H-1,2,4-triazol-1-yl)benzamido)benzoate (TPB) was a 1,2,4-triazole benzoyl arylamine derivative with excellent antifungal activity, especially against Gaeumannomyces graminis var. tritici (Ggt). Its mechanism of action was investigated by transmission electron microscopy (TEM) observation, assays of sterol composition, cell membrane permeability, intracellular ATP and mitochondrial membrane potential, and mPTP permeability, ROS measurement, RNA sequencing (RNA-seq) analysis. RESULTS: TPB interfered with ergosterol synthesis, reducing ergosterol content, increasing toxic intermediates, and finally causing biomembrane disruption such as increasing cell membrane permeability and content leakage, and destruction of organelle membranes such as coarse endoplasmic reticulum and vacuole. Moreover, TPB destroyed the function of adenine nucleotide transferase (ANT), leading to ATP transport obstruction in mitochondria, inhibiting mPTP opening, inducing intracellular ROS accumulation and mitochondrial membrane potential loss, finally resulting in mitochondrial damage including mitochondria swelled, mitochondrial membrane dissolved, and cristae destroyed and reduced. RNA-seq analyses showed that TPB increased the expression of ERG11, ERG24, ERG6, ERG5, ERG3 and ERG2 genes in ergosterol synthesis pathway, interfered with the expression of genes (NDUFS5, ATPeV0E, NCA2 and Pam17) related to mitochondrial structure, and inhibited the expression of genes (WrbA and GST) related to anti-oxidative stress. CONCLUSIONS: TPB exhibited excellent antifungal activity against Ggt by inhibiting ergosterol synthesis and destroying ANT function. So, TPB was a novel compound with dual-target mechanism of action and can be considered a promising novel fungicide for the control of wheat Take-all. The results provided new guides for the structural design of active compounds and powerful tools for pathogen resistance management. © 2023 Society of Chemical Industry.

Spatial proximity of tumor-immune interactions predicts patient outcome in hepatocellular carcinoma.

BACKGROUND AND AIMS: The fitness and viability of a tumor ecosystem are influenced by the spatial organization of its cells. We aimed to study the structure, architecture, and cell-cell dynamics of the heterogeneous liver cancer tumor microenvironment using spatially resolved multiplexed imaging. APPROACH AND RESULTS: We performed co-detection by indexing multiplexed immunofluorescence imaging on 68 HCC biopsies from Thai patients [(Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC)] as a discovery cohort, and then validated the results in an additional 190 HCC biopsies from Chinese patients [Liver Cancer Institute (LCI)]. We segmented and annotated 117,270 and 465,632 cells from the TIGER-LC and LCI cohorts, respectively. We observed 4 patient groups of TIGER-LC (IC1, IC2, IC3, and IC4) with distinct tumor-immune cellular interaction patterns. In addition, patients from IC2 and IC4 had much better overall survival than those from IC1 and IC3. Noticeably, tumor and CD8 + T-cell interactions were strongly enriched in IC2, the group with the best patient outcomes. The close proximity between the tumor and CD8 + T cells was a strong predictor of patient outcome in both the TIGER-LC and the LCI cohorts. Bulk transcriptomic data from 51 of the 68 HCC cases were used to determine tumor-specific gene expression features of our classified subtypes. Moreover, we observed that the presence of immune spatial neighborhoods in HCC as a measure of overall immune infiltration is linked to better patient prognosis. CONCLUSIONS: Highly multiplexed imaging analysis of liver cancer reveals tumor-immune cellular heterogeneity within spatial contexts, such as tumor and CD8 + T-cell interactions, which may predict patient survival.

Adapting the inoculation methods of kiwifruit canker disease to identify efficient biocontrol bacteria from branch microbiome.

Pseudomonas syringae pv. actinidiae (Psa), the bacterium that causes kiwifruit bacterial canker, is a common field occurrence that is difficult to control globally. Currently, exploring the resources for efficient biocontrol bacteria is a hot spot in the field. The common strategy for isolating biocontrol bacteria is to directly isolate biocontrol bacteria that can secrete diffusible antibacterial substances, most of which are members of Bacillus, Pseudomonas and Streptomycetaceae, from disease samples or soil. Here, we report a new approach by adapting the typical isolation methods of kiwifruit canker disease to identify efficient biocontrol bacteria from the branch microbiome. Using this unique approach, we isolated a group of kiwifruit biocontrol agents (KBAs) from the branch microbiome of Psa-resistant varieties. Thirteen of these showed no antagonistic activity in vitro, which depends on the secretion of antibacterial compounds. However, they exhibited antibacterial activity via cell-to-cell contacts mimicked by co-culture on agar plates. Through biocontrol tests on plants, two isolates, KBA13 and KBA19, demonstrated their effectiveness by protecting kiwifruit branches from Psa infection. Using KBA19, identified as Pantoea endophytica, as a representative, we found that this bacterium uses the type VI secretion system (T6SS) as the main contact-dependent antibacterial weapon that acts via translocating toxic effector proteins into Psa cells to induce cell death, and that this capacity expressed by KBA19 is common to various Psa strains from different countries. Our findings highlight a new strategy to identify efficient biocontrol agents that use the T6SS to function in an antibacterial metabolite-independent manner to control wood diseases.

Study on articular surface morphology of atlantoaxial lateral mass based on differential manifold.

OBJECTIVES: To propose a surface reconstruction algorithm based on a differential manifold (a space with local Euclidean space properties), which can be used for processing of clinical images and for modeling of the atlantoaxial joint. To describe the ideal anatomy of the lateral atlantoaxial articular surface by measuring the anatomical data. METHODS: Computed tomography data of 80 healthy subjects who underwent cervical spine examinations at our institution were collected between October 2019 and June 2022, including 46 males and 34 females, aged 37.8 ± 5.1 years (28-59 years). A differential manifold surface reconstruction algorithm was used to generate the model based on DICOM data derived by Vision PACS system. The lateral mass articular surface was measured and compared in terms of its sagittal diameter, transverse diameter, articular surface area, articular curvature and joint space height. RESULTS: There was no statistically significant difference between left and right sides of the measured data in normal adults (P > 0.05). The atlantoaxial articular surface sagittal diameter length was (15.83 ± 1.85) and (16.22 ± 1.57) mm on average, respectively. The transverse diameter length of the articular surface was (16.29 ± 2.16) and (16.49 ± 1.84) mm. The lateral articular surface area was (166.53 ± 7.69) and (174.48 ± 6.73) mm2 and the curvature was (164.03 ± 5.27) and (153.23 ± 9.03)°, respectively. The joint space height was 3.05 ± 0.11mm, respectively. There is an irregular articular space in the lateral mass of atlantoaxial, and both upper and lower surfaces of the articular space are concave. A sagittal plane view shows that the inferior articular surface of the atlas is mainly concave above; however, the superior articular surface of the axis is mainly convex above. In the coronal plane, the inferior articular surface of the atlas is mostly concave above, with most concave vertices located in the medial region, and the superior articular surface of the axis is mainly concave below, with most convex vertices located centrally and laterally. CONCLUSION: A differential manifold algorithm can effectively process atlantoaxial imaging data, fit and control mesh topology, and reconstruct curved surfaces to meet clinical measurement applications with high accuracy and efficiency; the articular surface of the lateral mass of atlantoaxial mass in normal adults has relatively constant sagittal diameter, transverse diameter and area. The distance difference between joint spaces is small, but the shape difference of articular surfaces differs greatly.

Pan-viral serology uncovers distinct virome patterns as risk predictors of hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

This study evaluates the pan-serological profiles of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) compared to several diseased and non-diseased control populations to identify risk factors and biomarkers of liver cancer. We used phage immunoprecipitation sequencing, an anti-viral antibody screening method using a synthetic-phage-displayed human virome epitope library, to screen patient serum samples for exposure to over 1,280 strains of pathogenic and non-pathogenic viruses. Using machine learning methods to develop an HCC or iCCA viral score, we discovered that both viral scores were positively associated with several liver function markers in two separate at-risk populations independent of viral hepatitis status. The HCC score predicted all-cause mortality over 8 years in patients with chronic liver disease at risk of HCC, while the viral hepatitis status was not predictive of survival. These results suggest that non-hepatitis viral infections may contribute to HCC and iCCA development and could be biomarkers in at-risk populations.

Genome-wide profiling of transcription factor activity in primary liver cancer using single-cell ATAC sequencing.

Primary liver cancer (PLC) consists of two main histological subtypes; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). The role of transcription factors (TFs) in malignant hepatobiliary lineage commitment between HCC and iCCA remains underexplored. Here, we present genome-wide profiling of transcription regulatory elements of 16 PLC patients using single-cell assay for transposase accessible chromatin sequencing. Single-cell open chromatin profiles reflect the compositional diversity of liver cancer, identifying both malignant and microenvironment component cells. TF motif enrichment levels of 31 TFs strongly discriminate HCC from iCCA tumors. These TFs are members of the nuclear/retinoid receptor, POU, or ETS motif families. POU factors are associated with prognostic features in iCCA. Overall, nuclear receptors, ETS and POU TF motif families delineate transcription regulation between HCC and iCCA tumors, which may be relevant to development and selection of PLC subtype-specific therapeutics.