Immune cell infiltration and prognostic index in cervical cancer: insights from metabolism-related differential genes.

Background: Cervical cancer remains a significant gynecologic malignancy in both China and the United States, posing a substantial threat to women's lives and health due to its high morbidity and mortality rates. Altered energy metabolism and dysregulated mitochondrial function play crucial roles in the development, growth, metastasis, and recurrence of malignant tumors. In this study, we aimed to predict prognosis and assess efficacy of anti-tumor therapy in cervical cancer patients based on differential genes associated with mitochondrial metabolism. Methods: Transcriptomic data and clinical profiles of cervical cancer patients were retrieved from the TCGA and GEO databases. Differential gene-related cellular pathways were identified through GO, KEGG, and GSEA analyses. Prognostic indices were constructed using LASSO regression analysis. Immune cell infiltration was assessed using CIBERSORT and ssGSEA, and the correlation between immune checkpoint inhibitor genes and differential genes was examined. Tumor mutation load (TMB) and its association with prognostic indices were analyzed using nucleotide variant data from the TCGA database. Patient response to immunotherapy and sensitivity to antitumor drugs were determined using the TIDE algorithm and the oncoPredic algorithm, respectively. Results: A prognostic index based on metabolism-related differential genes was developed to predict the clinical outcome of cervical cancer patients, enabling their classification into two distinct subtypes. The prognostic index emerged as an independent risk factor for unfavorable prognosis. The high-index group exhibited a significantly worse overall prognosis, along with elevated tumor mutation burden (TMB), increased immune cell infiltration, and lower TIDE scores, indicating a potential benefit from immunotherapy. Conversely, the low-index group demonstrated increased sensitivity to metabolism-related antitumor agents, specifically multikinase inhibitors. Conclusion: The aim of this study was to develop a prognostic index based on differential genes associated with mitochondrial metabolism, which could be used to predict cervical cancer patients' prognoses. When combined with TIDE and TMB analyses, this prognostic index offers insights into the immune cell infiltration landscape, as well as the potential efficacy of immunotherapy and targeted therapy. Our analysis suggests that the Iron-Sulfur Cluster Assembly Enzyme (ISCU) gene holds promise as a biomarker for cervical cancer immunotherapy.

MARCH5-mediated downregulation of ACC2 promotes fatty acid oxidation and tumor progression in ovarian cancer.

Lipid metabolic reprogramming has been recognized as a hallmark of human cancer. Acetyl-CoA Carboxylases (ACCs) are key rate-limiting enzymes involved in fatty acid metabolism regulation by catalyzing the carboxylation of acetyl-CoA to malonyl-CoA. Previously, most studies focused on the role of ACC1 in fatty acid metabolism in cancer, while the function of ACC2 remains largely uncharacterized in human cancers, especially in ovarian cancer (OC). Here, we show that ACC2 was significantly downregulated in cancerous tissue of OC, and the downregulation of ACC2 is closely associated with lager tumor size, metastases and worse prognosis in OC patients. Downregulation of ACC2 promoted proliferation and metastasis of OC both in vitro and in vivo by enhancing FAO. Notably, mitochondria-associated ubiquitin ligase (MARCH5) was identified to interact with and downregulate ACC2 by ubiquitination and degradation in OC. Moreover, ACC2 downregulation-enhanced FAO contributed to the progression of OC promoted by MARCH5. In conclusion, our findings demonstrate that MARCH5-mediated downregulation of ACC2 promotes FAO and tumorigenesis in OC, suggesting MARCH5-ACC2 axis as a potent candidate for the treatment and prevention of OC.

WITHDRAWN: HCST Expression Distinguishes Immune-hot and Immune-cold Subtypes in Pancreatic Ductal Adenocarcinoma

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis.

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

Identification of HnRNP Family as Prognostic Biomarkers in Five Major Types of Gastrointestinal Cancer.

BACKGROUND: Heterogeneous nuclear ribonucleoproteins (hnRNPs), a large family of RNAbinding proteins, have been implicated in tumor progression in multiple cancer types. However, the expression pattern and prognostic value of hnRNPs in five gastrointestinal (GI) cancers, including gastric, colorectal, esophageal, liver, and pancreatic cancer, remain to be investigated. OBJECTIVE: The current research aimed to identify prognostic biomarkers of the hnRNP family in five major types of gastrointestinal cancer. METHODS: Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan-Meier Plotter were used to explore the hnRNPs expression levels concerning clinicopathological parameters and prognostic values. The protein level of hnRNPU was validated by immunohistochemistry (IHC) in human tissue specimens. Genetic alterations of hnRNPs were analyzed using cBioportal, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to illustrate the biological functions of co-expressed genes of hnRNPs. RESULTS: The vast majority of hnRNPs were highly expressed in five types of GI cancer tissues compared to their adjacent normal tissues, and mRNA levels of hnRNPA2B1, D, Q, R, and U were significantly different in various GI cancer types at different stages. In addition, Kaplan-Meier analysis revealed that the increased hnRNPs expression levels were correlated with better prognosis in gastric and rectal cancer patients (log-rank p < 0.05). In contrast, patients with high levels of hnRNPs exhibited a worse prognosis in esophageal and liver cancer (log-rank p < 0.05). Using immunohistochemistry, we further confirmed that hnRNPU was overexpressed in gastric, rectal, and liver cancers. In addition, hnRNPs genes were altered in patients with GI cancers, and RNA-related processing was correlated with hnRNPs alterations. CONCLUSION: We identified differentially expressed genes of hnRNPs in tumor tissues versus adjacent normal tissues, which might contribute to predicting tumor types, early diagnosis, and targeted therapies in five major types of GI cancer.

Air and surface contamination by SARS-CoV-2 virus in a tertiary hospital in Wuhan, China.

BACKGROUND: Few studies have explored air and surface contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthcare settings. METHODS: Air and surface samples were collected from the isolation wards and intensive care units designated for coronavirus disease 2019 (COVID-19) patients. Clinical data and the results of nasopharyngeal specimen and serum antibody testing were also collected for the patient sample. RESULTS: A total of 367 air and surface swab samples were collected from the patient care areas of 15 patients with mild COVID-19 and nine patients with severe/critical COVID-19. Only one air sample taken during the intubation procedure tested positive. High-touch surfaces were slightly more likely to be contaminated with SARS-CoV-2 RNA than low-touch surfaces. Contamination rates were slightly higher near severe/critical patients than near mild patients, although this difference was not statistically significant (p > 0.05). Surface contamination was still found near the patients with both positive IgG and IgM. CONCLUSIONS: Air and surface contamination with viral RNA was relatively low in these healthcare settings after the enhancement of infection prevention and control. Environmental contamination could still be found near seroconverted patients, suggesting the need to maintain constant vigilance in healthcare settings to reduce healthcare-associated infection during the COVID-19 pandemic.