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World Journal of Hepatology May 2024Liver cancer, primarily hepatocellular carcinoma, remains a global health challenge with rising incidence and limited therapeutic options. Genetic factors play a pivotal... (Review)
Review
Liver cancer, primarily hepatocellular carcinoma, remains a global health challenge with rising incidence and limited therapeutic options. Genetic factors play a pivotal role in the development and progression of liver cancer. This state-of-the-art paper provides a comprehensive review of the current landscape of genetic screening strategies for liver cancer. We discuss the genetic underpinnings of liver cancer, emphasizing the critical role of risk-associated genetic variants, somatic mutations, and epigenetic alterations. We also explore the intricate interplay between environmental factors and genetics, highlighting how genetic screening can aid in risk stratification and early detection using liquid biopsy, and advancements in high-throughput sequencing technologies. By synthesizing the latest research findings, we aim to provide a comprehensive overview of the state-of-the-art genetic screening methods for liver cancer, shedding light on their potential to revolutionize early detection, risk assessment, and targeted therapies in the fight against this devastating disease.
PubMed: 38818292
DOI: 10.4254/wjh.v16.i5.716 -
World Journal of Hepatology May 2024Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer associated with an appalling prognosis. The diagnosis and management of this entity... (Review)
Review
Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer associated with an appalling prognosis. The diagnosis and management of this entity have been challenging to physicians, radiologists, surgeons, pathologists, and oncologists alike. The diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin, a progenitor cell marker, have been explored recently. With a better understanding of biology and the clinical course of cHCC-CCA, newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare disease. In this review, we give an account of the recent developments in the pathology, diagnostic approach, and management of cHCC-CCA.
PubMed: 38818284
DOI: 10.4254/wjh.v16.i5.766 -
Journal of Cancer 2024Tumor angiogenesis is closely related to the progression of clear cell renal cell carcinoma (ccRCC). Long non-coding RNAs (lncRNAs) regulating angiogenesis could be...
Tumor angiogenesis is closely related to the progression of clear cell renal cell carcinoma (ccRCC). Long non-coding RNAs (lncRNAs) regulating angiogenesis could be potential biomarkers for predicting ccRCC prognosis. With this study, we aimed to construct a prognostic model based on lncRNAs and explore its underlying mechanisms. RNA data and clinical information were obtained from The Cancer Genome Atlas (TCGA) database. Angiogenesis-related genes (ARGs) were extracted from the Molecular Signatures database. Pearson correlation and LASSO and COX regression analyses were performed to identify survival-related AR-lncRNAs (sAR-lncRNAs) and construct a prognostic model. The predictive power of the prognostic model was verified according to Kaplan‒Meier curve, receiver operating characteristic (ROC) curve and nomogram analyses. The correlation between the prognostic model and clinicopathological characteristics was assessed via univariate and multivariate analyses. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was subsequently performed to elucidate the mechanisms of the sAR-lncRNAs. In vitro qPCR, immunohistochemistry, migration and invasion assays were conducted to confirm the angiogenic function of sAR-lncRNAs. Three sAR-lncRNAs were used to construct a prognostic model. The model was moderately accurate in predicting 1- , 3- and 5-year ccRCC prognosis, and the risk score according to this model was closely related to clinicopathological characteristics such as T grade and T stage. A nomogram was constructed to precisely estimate the overall survival of ccRCC patients. KEGG enrichment analysis indicated that the MAPK and Notch pathways were highly enriched in high-risk patients. Additionally, we found that the expression of the lncRNAs AC005324.4 and AC104964.4 in the prognostic model was lower in ccRCC cell lines and cancer tissues than in the HK-2 cell line and paracancerous tissues, while the expression of the lncRNA AC087482.1 showed the opposite trend. In a coculture model, knockdown of lncRNA AC005324.4 and lncRNA AC104964.4 significantly promoted the migration and invasion of human umbilical vein endothelial cells (HUVECs), but siR-AC087482.1 transfection alleviated these effects. We constructed a prognostic model based on 3 sAR-lncRNAs and validated its value in clinicopathological characteristics and prognostic prediction of ccRCC patients, providing a new perspective for ccRCC treatment decision making.
PubMed: 38817877
DOI: 10.7150/jca.94685 -
Journal of Cancer 2024Stomach adenocarcinoma (STAD) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Cancer-testis antigens (CTAs) participate...
Stomach adenocarcinoma (STAD) is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Cancer-testis antigens (CTAs) participate in the pathogenesis and development of multiple cancers and are aberrantly overexpressed in various types of cancer. This study aimed to develop a CTA-related gene signature (CTARSig) to predict prognosis in STAD patients and explore its underlying mechanisms. We performed differential and prognostic analyses of CTA-related genes and constructed a CTA-related signature (CTARSig) along with a novel nomogram to predict the prognosis of patients with STAD based on the Cox and The Least Absolute Shrinkage and Selection Operator. CTARSig was further validated in an external cohort (GSE84437). Additionally, univariate and multivariate Cox regression, as well as receiver operating characteristic (ROC) analyses, were performed to assess the CTARSig systematically. Single-sample gene set enrichment analysis and ESTIMATE were used to characterise the Tumor Immune Microenvironment (TIME) in patients with STAD. Furthermore, Gene Set Variation Analysis, Kyoto Encyclopedia of Genes and Genomes, and Gene Ontology analyses revealed the biological functions and signalling pathways associated with CTARSig. Finally, the human gastric cancer cell lines, HCG-27 and AGS, were used for and experiments, respectively, to further validate the role of ELOVL4. Eleven CTA-related genes were identified to construct the CTARSig. Kaplan-Meier curves, independent prognostic analysis, and ROC curves revealed that CTARSig could better predict survival in patients with STAD. Moreover, in our study, we demonstrated that ELOVL4 is upregulated in gastric cancer tissues and that its high expression is associated with poor survival. Additionally, and experiments demonstrated that ELOVL4 promotes the metastatic and invasive potential of STAD cells, suggesting it may be a potential therapeutic target for STAD. In this study, a novel signature associated with CTAs was constructed for STAD, which may be a good predictor of patient prognosis. Thus, ELOVL4 may be a potential therapeutic target for gastric cancer. This study provides new insights into the potential roles of CTAs in gastric cancer.
PubMed: 38817874
DOI: 10.7150/jca.91842 -
Journal of Cancer 2024The innate immune system serves as the body's primary physiological defense against the intrusion of pathogenic microorganisms, playing a pivotal role in restricting...
The innate immune system serves as the body's primary physiological defense against the intrusion of pathogenic microorganisms, playing a pivotal role in restricting viral infections. However, current research on the interplay between innate immune pathways and cancer is limited, with reported effects often inconsistent. Therefore, we aimed to elucidate the relationship between innate immune pathways and tumors through an amalgamation of bioinformatics and extensive data analysis. Conducting a pan-cancer analysis encompassing expression, genomic alterations, and clinical prognosis, we identified a close association between the innate immune pathway and cholangiocarcinoma. Subsequently, our focus shifted to unraveling the role of innate immune pathway proteins in cholangiocarcinoma. TIMER database analysis showed that the innate immune pathway predominantly influences the infiltration of macrophages and B cells in cholangiocarcinoma. Additionally, gene ontology (GO) and pathway analyses were performed for significantly differentially expressed genes correlated with the innate immune pathway in cholangiocarcinoma. Single-cell transcriptome analysis in cholangiocarcinoma demonstrated that genes in the innate immune pathway are primarily expressed in malignant cells, endothelial cells, monocytes and macrophages. To further validate the expression of proteins in the innate immune pathway in the tumor tissues of patients with cholangiocarcinoma, tumor tissue slices from patients with liver intrahepatic cholangiocarcinoma and normal tissue slices from the HPA database were analyzed. These results indicated pronounced activation of the innate immune pathway in the tumor tissues of patients with cholangiocarcinoma. Finally, proteomic data from patients with or without intrahepatic cholangiocarcinoma metastasis were analyzed. The results revealed a significant correlation between the expression and phosphorylation of IKKε and the occurrence of intrahepatic cholangiocarcinoma metastasis. These findings not only demonstrate the significance of the innate immune pathway in cholangiocarcinoma but also its potential as a prospective prognostic biomarker and therapeutic target for this malignancy.
PubMed: 38817870
DOI: 10.7150/jca.94194 -
World Journal of Gastroenterology May 2024Lactate, previously considered a metabolic byproduct, is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment. Further...
BACKGROUND
Lactate, previously considered a metabolic byproduct, is pivotal in cancer progression and maintaining the immunosuppressive tumor microenvironment. Further investigations confirmed that lactate is a primary regulator, introducing recently described post-translational modifications of histone and non-histone proteins, termed lysine lactylation. Pancreatic adenocarcinomas are characterized by increased glycolysis and lactate accumulation. However, our understanding of lactylation-related genes in pancreatic adenocarcinomas remains limited.
AIM
To construct a novel lactylation-related gene signature to predict the survival of patients with pancreatic cancer.
METHODS
RNA-seq and clinical data of pancreatic adenocarcinoma (PDAC) were obtained from the GTEx (Genotype-Tissue Expression) and TCGA (The Cancer Genome Atlas) databases Xena Explorer, and GSE62452 datasets from GEO. Data on lactylation-related genes were obtained from publicly available sources. Differential expressed genes (DEGs) were acquired by using R package "DESeq2" in R. Univariate COX regression analysis, LASSO Cox and multivariate Cox regressions were produced to construct the lactylation-related prognostic model. Further analyses, including functional enrichment, ESTIMATE, and CIBERSORT, were performed to analyze immune status and treatment responses in patients with pancreatic cancer. PDAC and normal human cell lines were subjected to western blot analysis under lactic acid intervention; two PDAC cell lines with the most pronounced lactylation were selected. Subsequently, RT-PCR was employed to assess the expression of LRGs genes; SLC16A1, which showed the highest expression, was selected for further investigation. SLC16A1-mediated lactylation was analyzed by immunofluorescence, lactate production analysis, colony formation, transwell, and wound healing assays to investigate its role in promoting the proliferation and migration of PDAC cells. validation was performed using an established tumor model.
RESULTS
In this study, we successfully identified 10 differentially expressed lactylation-related genes (LRGs) with prognostic value. Subsequently, a lactylation-related signature was developed based on five OS-related lactylation-related genes ( and ) using Lasso Cox hazard regression analysis. Subsequently, we evaluated the clinical significance of the lactylation-related genes in pancreatic adenocarcinoma. A comprehensive examination of infiltrating immune cells and tumor mutation burden was conducted across different subgroups. Furthermore, we demonstrated that SLC16A1 modulates lactylation in pancreatic cancer cells through lactate transport. Both and experiments showed that decreasing SLC16A1 Level and its lactylation significantly inhibited tumor progression, indicating the potential of targeting the SLC16A1/Lactylation-associated signaling pathway as a therapeutic strategy against pancreatic adenocarcinoma.
CONCLUSION
We constructed a novel lactylation-related prognostic signature to predict OS, immune status, and treatment response of patients with pancreatic adenocarcinoma, providing new strategic directions and antitumor immunotherapies.
Topics: Humans; Pancreatic Neoplasms; Prognosis; Cell Line, Tumor; Tumor Microenvironment; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Monocarboxylic Acid Transporters; Protein Processing, Post-Translational; Adenocarcinoma; Lactic Acid; Symporters; Cell Proliferation; Gene Expression Profiling; Male; Carcinoma, Pancreatic Ductal; Female; Animals; Transcriptome
PubMed: 38817665
DOI: 10.3748/wjg.v30.i19.2575 -
World Journal of Gastroenterology May 2024Immune checkpoint inhibitor therapy has dramatically improved patient prognosis, and thereby transformed the treatment in various cancer types including esophageal... (Review)
Review
Immune checkpoint inhibitor therapy has dramatically improved patient prognosis, and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma (ESCC) in the past decade. Monoclonal antibodies that selectively inhibit programmed cell death-1 (PD-1) activity has now become standard of care in the treatment of ESCC in metastatic settings, and has a high expectation to provide clinical benefit during perioperative period. Further, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody. Well understanding of the existing evidence of immune-based treatments for ESCC, as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant, adjuvant, and metastatic diseases, may provide future prospects of ESCC treatment for better patient outcomes.
Topics: Humans; Esophageal Neoplasms; Immune Checkpoint Inhibitors; Esophageal Squamous Cell Carcinoma; Neoadjuvant Therapy; CTLA-4 Antigen; Immunotherapy; Programmed Cell Death 1 Receptor; Treatment Outcome; Chemotherapy, Adjuvant; Antineoplastic Combined Chemotherapy Protocols; Prognosis; Neoplasm Recurrence, Local
PubMed: 38817664
DOI: 10.3748/wjg.v30.i19.2496 -
World Journal of Gastroenterology May 2024Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis (AP) but can be detected in various other diseases associated with lipase leakage... (Observational Study)
Observational Study
BACKGROUND
Increased lipase level is a serological hallmark of the diagnosis of acute pancreatitis (AP) but can be detected in various other diseases associated with lipase leakage due to inflammation of organs surrounding the pancreas or reduced renal clearance and/or hepatic metabolism. This non-pancreatic hyperlipasemia (NPHL) is puzzling for attending physicians during the diagnostic procedure for AP. It would be clinically beneficial to identify the clinical and laboratory variables that hinder the accuracy of lipase diagnosis with the aim of improve it. A more precise description of the NPHL condition could potentially provide prognostic factors for adverse outcomes which is currently lacking.
AIM
To perform a detailed clinical and laboratory characterization of NPHL in a large prospective patient cohort with an assessment of parameters determining disease outcomes.
METHODS
A Hungarian patient cohort with serum lipase levels at least three times higher than the upper limit of normal (ULN) was prospectively evaluated over 31 months. Patients were identified using daily electronic laboratory reports developed to support an ongoing observational, multicenter, prospective cohort study called the EASY trial (ISRCTN10525246) to establish a simple, easy, and accurate clinical scoring system for early prognostication of AP. Diagnosis of NPHL was established based on ≥ 3 × ULN serum lipase level in the absence of abdominal pain or abdominal imaging results characteristic of pancreatitis.
RESULTS
A total of 808 patients [male, = 420 (52%); median age (IQR): 65 (51-75) years] were diagnosed with ≥ 3 × ULN serum lipase levels. A total of 392 patients had AP, whereas 401 had NPHL with more than 20 different etiologies. Sepsis and acute kidney injury (AKI) were the most prevalent etiologies of NPHL (27.7% and 33.2%, respectively). The best discriminative cut-off value for lipase was ≥ 666 U/L (sensitivity, 71.4%; specificity, 88.8%). The presence of AKI or sepsis negatively affected the diagnostic performance of lipase. NPHL was associated with a higher in-hospital mortality than AP (22.4% 5.1%, < 0.001). In multivariate binary logistic regression, not lipase but increased amylase level (> 244 U/L) and neutrophil-to-lymphocyte ratio (NLR) (> 10.37, OR: 3.71, 95%CI: 2.006-6.863, < 0.001), decreased albumin level, age, and presence of sepsis were independent risk factors for in-hospital mortality in NPHL.
CONCLUSION
NPHL is a common cause of lipase elevation and is associated with high mortality rates. Increased NLR value was associated with the highest mortality risk. The presence of sepsis/AKI significantly deteriorates the serological differentiation of AP from NPHL.
Topics: Humans; Lipase; Male; Female; Middle Aged; Prospective Studies; Pancreatitis; Aged; Prognosis; Hungary; Biomarkers; Adult
PubMed: 38817657
DOI: 10.3748/wjg.v30.i19.2538 -
World Journal of Gastroenterology May 2024Heartburn is a common symptom shared by both gastroesophageal reflux disease (GERD) and functional heartburn (FHB), which can make it challenging to differentiate...
Heartburn is a common symptom shared by both gastroesophageal reflux disease (GERD) and functional heartburn (FHB), which can make it challenging to differentiate between the two conditions. However, examining oral manifestations of GERD can be a cost-effective and readily available method to aid in this differentiation process. It may serve as a valuable tool in distinguishing GERD from FHB.
Topics: Humans; Gastroesophageal Reflux; Saliva; Heartburn; Pepsin A; Diagnosis, Differential; Biomarkers
PubMed: 38817654
DOI: 10.3748/wjg.v30.i19.2612 -
World Journal of Cardiology May 2024In this editorial we comment on the article by Kuwahara , published in the recent issue of the . In this interesting paper, the authors showed a correlation between...
In this editorial we comment on the article by Kuwahara , published in the recent issue of the . In this interesting paper, the authors showed a correlation between portal vein pulsatility ratio, examined by bedside ultrasonography, and prognosis of hospitalized patients with acute heart failure. Systemic congestion is being notoriously underdetected in the acutely ill population with conventional methods like clinical examination, biomarkers, central venous pressure estimation and X-rays. However, congestion should be a key therapeutic target due to its deleterious effects to end organ function and subsequently patient prognosis. Doppler flow assessment of the abdominal veins is gaining popularity worldwide, as a valuable tool in estimating comprehensively congestion and giving a further insight into hemodynamics and patient management.
PubMed: 38817642
DOI: 10.4330/wjc.v16.i5.221