Infectious Agents and Cancer最新文献

Background: Successful antiviral therapy significantly decreases the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). Alpha-fetoprotein (AFP) in the serum is a valuable early indicator of HCC. However, it is unclear whether different antiviral medications have varying effects on AFP levels. The purpose of this study was to evaluate this issue in those treated with entecavir (ETV) versus tenofovir disoproxil fumarate (TDF).

Methods: We prospectively enrolled treatment-naive CHB adults who commenced treatment with ETV or TDF. Their changes in biochemical, virological, and fibrosis parameters and the elevation of AFP or development of HCC during follow-up were analyzed.

Results: A total of 1942 CHB patients were included (10-90% follow-up time 3-60 months), and 104 patients with elevated AFP (5.3%) and 27 patients with HCC development (1.4%) were identified during the follow-up. The difference in the cumulative incidence of AFP abnormalities and HCC was statistically significant between patients who received ETV or TDF therapy. Multivariate Cox regression showed that elevated liver stiffness with shear wave elastography (Hazard ratio (HR) = 1.05, 95% Confidence interval (CI) 1.03-1.08, P < 0.001) and abnormal AFP at baseline (HR = 1.00, 95% CI 1.00-1.00, P < 0.001) were independent risk factors for abnormal AFP in CHB patients, while shear wave elastography (HR = 1.07, 95% CI 1.02-1.12, P < 0.001) was also independent risk factor for HCC. Similar results were obtained after propensity score matching (PSM) analysis. The combination of shear wave elastography (SWE), mPage-B score, age and type 2 diabetes mellitus had an area under the curve of 0.838 (P < 0.001) in predicting the occurrence of HCC.

Conclusions: Similar AFP elevation and HCC development rates were observed in CHB patients treated with ETV or TDF. Elevated SWE and abnormal AFP at baseline were independent risk factors for abnormal AFP in CHB patients.

Background: Colorectal cancer (CRC) ranks among the frequently occurring malignant neoplasms affecting the gastrointestinal tract. This study aimed to explore JAK-STAT signaling pathway related genes in CRC and establish a new prognostic model.

Methods: The data set used in this study is from a public database. JAK-STAT-differentially expressed genes (DEGs) were identified through differential expression analysis and weighted gene co-expression network analysis (WGCNA). Prognostic genes were selected from JAK-STAT-DEGs through Mendelian randomization (MR), univariate Cox regression, and least absolute shrinkage and selection operator (LASSO) analyses. The expressions of prognostic genes were verified by RT-qPCR. Then, a risk model was built and validated by the GSE39582. Independent prognostic factors were screened underlying risk scores and different clinical indicators, resulting in the construction of a nomogram. Additionally, immune infiltration, immune scores and immune checkpoint inhibitors analyses and gene set enrichment analysis (GSEA) were carried out.

Results: The 3,668 JAK-STAT-DEGs were obtained by intersection of 5826 CRC-DEGs and 9766 JAK-STAT key module genes. Five prognostic genes were selected (ANK3, F5, FAM50B, KLHL35, MPP2), and their expressions were significantly different between CRC and control groups. A risk model was constructed according to prognostic genes and verified by GSE39582. In addition, the nomogram exhibited superior predictive accuracy for CRC. Furthermore, immune analysis results indicated a notable positive correlation between risk score and the scores of immune (R = 0.486), stromal (R = 0.309), and ESTIMATE (R = 0.422). Immune checkpoint inhibitor ADORA2A (Cor = 0.483263) exhibited the strongest positive correlation with risk score. And MPP2 exhibited the most potent activating influence on the cell cycle pathway, whereas ANK3 demonstrated the most significant inhibitory effect within the apoptosis pathway.

Conclusions: A new JAK-STAT related CRC prognostic model was constructed and validated, which possessed an underlying predictive potential for CRC patients' prognosis and could potentially enhance tailored guidance for immunotherapy.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, with approximately 800,000 deaths worldwide each year. Owing to the atypical early symptoms and characteristics of HCC, over 80% of HCC patients cannot receive curative treatment. The treatment of HCC is facing a bottleneck, and new treatment methods are urgently needed. Since the pathogenesis of HCC is not yet clear, identifying the molecular mechanisms and therapeutic targets related to it is crucial. Centromeres are considered special deoxyribonucleic acid (DNA) sequences with highly repetitive sequences that are physically connected to the spindle during cell division, ensuring equal division of genetic material between daughter cells. The numerous proteins that aggregate on this sequence during cell division are called centromere proteins (CENPs). Currently, numerous studies have shown that CENPs are abnormally expressed in tumor cells and are associated with patient prognosis. The abnormal expression of CENPs is a key cause of chromosomal instability. Furthermore, chromosomal instability is a common characteristic of the majority of tumors. Chromosomal instability can lead to uncontrolled and sustained division and proliferation of malignant tumors. Therapeutic plans targeting CENPs play important roles in the treatment of HCC. For example, small ribonucleic acid (RNA) can silence CENP expression and prevent the occurrence and development of liver cancer. In recent years, studies of HCC-targeting CENPs have gradually increased but are still relatively novel, requiring further systematic elaboration. In this review, we provide a detailed introduction to the characteristics of CENPs and discuss their roles in HCC. In addition, we discuss their application prospects in future clinical practice.

Purpose: To investigate the patterns of failure and prognosis in recurrent or metastatic nasopharyngeal carcinoma (rmNPC) according to Epstein-Barr virus-DNA (EBV-DNA) status.

Methods: We included NPC patients who were diagnosed with locoregional recurrence (LRR) and/(or) distant metastasis (DM) between January 2017 and June 2024. Receiver operating characteristic analysis, Chi-square test, Wilcoxon rank sum test, Kaplan-Meier method, and Multivariate Cox regression analyses were used for statistical analysis.

Results: This study involved 108 patients, including 105 (97.2%) who had EBV-DNA detectable at the initial diagnosis of NPC. Regarding progression patterns, 34 patients (31.5%) experienced only LRR, while 60 patients (55.6%) had only DM. LRR followed by DM was observed in 5 (4.6%) patients, DM followed by LRR occurred in 2 (1.8%) patients, and both LRR and DM were presented simultaneously in 7 (6.5%) patients. EBV-DNA positivity rates significantly differed between LRR and DM patients, at 76.9% and 97.1% respectively (P = 0.003). A significant difference was also observed in EBV-DNA levels, with a median level of 413 copies/mL for LRR and 6,550 copies/mL for DM (P < 0.001). While the EBV-DNA positivity rate did not differ significantly between oligometastatic disease and polymetastatic disease (P = 0.493), the levels were significantly elevated in the polymetastatic disease group than the oligometastatic disease group (P < 0.001). Multivariate analysis showed that liver metastasis (P = 0.012) and EBV-DNA levels ≥ 3,525 copies/mL at progression (P = 0.009) independently correlated with poorer overall survival.

Conclusions: Our study provides substantial evidence linking higher EBV-DNA levels with disease failure patterns and identifies liver metastasis and EBV-DNA levels at disease progression as independent prognostic factors for poorer overall survival in rmNPC patients.

Background: It is crucial to identify post-operative patients with HPV infection who are at high risk for residual/recurrent disease. This study aimed to evaluate the association between HPV integration and clinical outcomes in HPV-positive women after cervical conization, as well as to identify HPV integration breakpoints.

Methods: This retrospective study analyzed data of 791 women who underwent cervical conization for cervical intraepithelial neoplasia grades 2-3 (CIN2-3) between September 2019 and September 2023, sourced from the Fujian and Hubei cervical lesion screening cohorts. Among these, 73 women with HPV infection post-conization underwent HPV integration test within 3 months after a positive HPV test. HPV integration test was performed using the high-throughput viral integration detection (HIVID), a sensitive method for genome-wide survey of HPV integration breakpoints.

Results: Among the 73 participants with HPV infection post-conization, 10 cases (13.7%) were positive for HPV integration. The logistic regression analysis showed a higher residual/recurrent lesions risk in patients with HPV integration (OR = 3.917, p = 0.048). According to the Kaplan-Meier analysis, age ≥ 45 years (p = 0.016) and HPV integration (p = 0.035) were associated with a higher risk of residual/recurrent CIN at the 1-year follow-up. HPV 52 accounted for the majority of HPV integration genotype (3/10, 30.0%). Surprisingly, HPV 16 had the highest number of HPV average integration sequencing reads (n = 129), followed by HPV 31, 58, 52, 59, 35, and 39. The study also identified 13 HPV breakpoints, including TP63, TLR4, USP10, etc. CONCLUSIONS: HPV integration was identified as an independent risk factor for residual/recurrent CIN in HPV-positive women post-conization. Women with positive HPV integration should pay attention to careful post-treatment follow-up.

Both women and men are now confronted with the grave threat of cancers caused by the human papillomavirus (HPV). It is estimated that 80% of women may encounter HPV over their lives. In the preponderance of cases involving anal, head and neck, oral, oropharyngeal, penile, vaginal, vulvar, and cervical malignancies, high-risk HPV (HR-HPV) is the causative agent. In 2019, HPV is believed to have been the cause of 620,000 new cases of cancer in women and 70,000 new cases of cancer in men worldwide. The bulk of the 530,000 cervical cancer cases (~ 270,000 fatalities) caused by HPV infection (86% of cases, 88% of deaths) happen in poor nations each year. Lipid metabolism is crucial in HPV infection and cancer development related to HPV. One of the most noticeable metabolic abnormalities in cancer is lipid metabolism reprogramming, in which cancer cells dysregulate lipid metabolism to obtain sufficient energy, building blocks for cell membranes, and signaling molecules necessary for invasion, metastasis, proliferation, and survival. Moreover, HPV proteins' stimulation of lipid production in infected cells will probably have a significant effect on oncogenesis. In addition, lipids are critical in producing cellular energy, the epithelial-mesenchymal transition (EMT) process, and therapy resistance of HPV-related cancers (HRCs). Therefore, lipids are essential in HPV infection and HRC development and may also be an important target for new approaches associated with treatments during HPV infection or cancer development. This review study looked at the role of lipids and lipid-lowering drugs in HPV and related cancers.

Background: The differential diagnosis between adult systemic EBV-positive T-cell lymphoproliferative disorders (EBV⁺ T-LPD) and angioimmunoblastic T-cell lymphoma (AITL) with multiple EBV infections is difficult, and distinguishing between the two has become a diagnostic challenge for pathologists. Given that the clinical treatment plans are different, an accurate diagnosis is a prerequisite to ensure effective treatment, therefore, it is extremely necessary and meaningful to find effective pathological indicators for distinguishing between two diseases.

Methods: We present a retrospective study comparing 7 cases of adult EBV⁺ T-LPD and 16 cases of AITL with multiple EBV infections diagnosed at our institution from 2017 to 2022. Differences in immunophenotype, type of EBV-infected cells, clonality and gene mutations between the two groups of cases were compared by immunohistochemical staining, double-label staining, TCR gene rearrangement and next-generation sequencing analysis.

Results: 7 cases of adult EBV⁺ T-LPD: all cases had no more than 1 T follicular helper (THF) marker was expressed, and there were significantly more EBER+/CD3 + cells than EBER+/CD20 + cells; 5 cases had mutation detection results, in which only 1 had the characteristic KMT2D mutation, 2 had TET2 mutations, and no common mutations such as DDX3X were detected.16 cases of AITL with multiple EBV infections: all cases were found to express at least 2 TFH markers, with 87% of them expressing at least 3 TFH markers., and had significantly more EBER+/CD20 + cells than EBER+/CD3 + cells; 4 cases had mutation test results, with mutated high-frequency genes being TET2 (100%, and all of them had 2 or more TET2 mutations) and RHOA G17V (100%), DNMT3A mutation occurred in 2 cases (50%), and IDH2 R172 mutation occurred in 1 case (25%).

Conclusions: We found that the expression pattern of TFH markers, the types of cells predominantly infected by EBV and the different mutations can all be used as effective pathological indicators for distinguishing between two diseases.

Background: Cancer is a significant global health issue due to its high incidence and mortality rates. In recent years, the relationship between the human microbiota and cancer has garnered attention across various medical fields. This includes research into the microbial communities that influence cancer development, tumor-associated microorganisms, and the interactions between the microbiome and tumor, collectively referred to as the oncobiome.

Methods: The negative effects of secondary metabolites extracted from selected multidrug-resistant Gram-negative bacteria within the cancer microbiota were evaluated. These effects included carcinogenicity, mutagenicity, hepatotoxicity, nephrotoxicity, and sperm deformities observed in albino rats after one month of oral ingestion of these microbial extracts.

Results: Our findings in the present investigation revealed that among the bacterial community derived from the microbiota, Gram-negative bacteria accounted for 74.87% the total microbiota (146 out of 195) and their spectrum including Escherichia sp. (n = 36, 24.66%) followed by Acinetobacter sp. (n = 34, 23.29%), Stenotrophomonas sp. (n = 29, 19.86%), Pseudomonas sp. (n = 26, 17.81%) and Serratia sp. (n = 21, 14.38%), as the most prevalent pathogens. All isolates derived from the cancer microbiome exhibited multidrug resistance to a large number of conventional therapies. Out of them Serratia sp. Esraa 1, Stenotrophomonas sp. Esraa 2, Acinetobacter sp. Esraa 3, Escherichia sp. Esraa 4 and Pseudomonas sp. Esraa 5 strains showed multidrug resistant profile against all antibiotic classes under study including penicillins, cephalosporins, carbapenems, fluoroquinolones, β-lactamase inhibitors combinations, folate synthesis pathway inhibitors, phosphonic, aminoglycosides, polymyxins, tetracyclines, macrolides, and chloramphenicol antibiotics. The adverse effects of oral ingestion of their metabolites were evaluated in albino rats. They induced pronounced carcinogenesis along with severe raise in the inflammatory cytokines, hepatotoxicity, nephrotoxicity, mutagenicity along with sperm deformities in treated animals. Moreover, all metabolites showed marked cytotoxicity against human normal cell lines; human mammary epithelial (MCF10A), human lung fibroblasts (WI38) and human dermal fibroblasts (HDFs).

Conclusion: These bacterial strains isolated from the cancer microbiome may play significant roles in inducing cancer, inflammation, mutagenesis, hepatotoxicity, nephrotoxicity, and sperm abnormalities, along with histopathological changes in the treated animal groups by orally administrated metabolites in compared to the untreated group.

Background: Helicobacter pylori (H. pylori) is a global infectious carcinogen. We aimed to evaluate the prevalence of H. pylori infection in the healthcare-utilizing population undergoing physical examinations at a tertiary hospital in Guangxi, China. Furthermore, gastroscopies were performed on selected participants to scrutinize the endoscopic features of H. pylori infection among asymptomatic individuals.

Subjects and methods: This study involved 22,769 participants who underwent H. pylori antibody serology screenings at the hospital between 2020 and 2023. The 14C-urea breath test was employed to determine the current H. pylori infection status of 19,307 individuals. Concurrently, 293 participants underwent gastroscopy to evaluate their endoscopic mucosal abnormalities. The risk correlation and predictive value of endoscopic mucosal traits, Hp infection status, and 14C-urea breath test(14C-UBT) outcomes were investigated in subsequent analyses.

Results: Serum Ure, CagA, and VacA antibodies were detected in 43.3%, 27.4%, and 23.6% of the 22,769 subjects that were screened, respectively. The population exhibited 27.5% and 17.2% positive rates for immune type I and II, respectively. Male participants exhibited lower positive rates of serum antibodies than females. The positive rates and predictive risks of the antibodies increased with age, and the highest positive rates were observed in the 50-60 age subgroup. Based on the outcomes of serological diagnostic techniques, it was observed that the positive rate was significantly higher compared to that of non-serological diagnostic methods, specifically the 14C-UBT results (43.3% versus 14.97%). Among the other cohort (n = 19,307), the 14C-UBT revealed a 14.97% positivity rate correlated with age. The 293 individuals who underwent gastroscopy from 14C-UBT Cohort were found to be at an increased risk of a positive breath test if they exhibited duodenal bulb inflammation, diffuse redness, or mucosal edema during the gastroscopy visit.

Conclusion: The prevalence of Helicobacter pylori infection is high among the population of Wuzhou, Guangxi, China. Type I H. pylori strains, distinguished by their enhanced virulence, are predominant in this region. In the framework of this population-based study, age has been identified as an independent risk factor for H. pylori infection. Additionally, distinct mucosal manifestations observed during gastroscopy can facilitate the identification of healthcare-utilizing individuals with active H. pylori infections.

Infectious Agents and Cancer journal has recently launched a new collection of papers about "Point-of-Care (POC) for HPV-related genital cancers" putting together some interesting works on the accuracy of HPV tests for screening. This editorial initiative gave us the opportunity to reflect on the relations between accuracy measures, prevalence and characteristics of the tested population in the case of HPV-based screening. In screening test evaluation, we look at the clinical accuracy of the test as an intrinsic characteristic of the assay, which interacts with the characteristics of the population, the result being the screening performance. In the case of HPV testing, the clinical accuracy should be conceptualized in two steps, the analytical accuracy of the assay for HPV infection and the biological link between HPV infection and the target disease, i.e. the high-grade cervical intraepithelial neoplasia (hgCIN). This approach highlights that just a few false positive cases result from a lack of analytical specificity while most derive from women who have the infection but it did not progress to hgCIN. In addition, increasing prevalence of hgCIN results in relevant increases of PPV only if due or associated with exposures which increase the progression from infection to hgCIN or the duration of the latter; while an increase due to a higher prevalence of HPV infection would only marginally affect PPV. This approach may help in modelling the performance of HPV-based cervical screening.