Infectious Agents and Cancer最新文献

Background: Breast cancer (BC) remains one of the most common malignancies worldwide. Many viruses have been linked to BC; namely, Human papillomavirus (HPV), Epstein-Barr virus (EBV) and Bovine leukemia virus (BLV). However, a causal role is yet to be established.

Objectives: To detect the prevalence of BLV, EBV and HPV sequences in BC tissue compared to BC-free tissue and correlate their presence with different pathological features of BC.

Subjects and methods: A retrospective case-control study was conducted on 75 FFPE (formalin fixed paraffin embedded) blocks of BC tissues and 25 of BC-free tissues obtained from Alexandria Main University Hospital pathology department archive. Demographic, medical, pathological data were retrieved from patients' archival records. Hormonal receptor status, Real-time PCR for viral detection and HPV genotyping were done. Statistical analysis was done using SPSS software. The Chi-square test, Fisher's Exact correction and Monte Carlo simulation were used for quantitative variables.

Results: Invasive ductal carcinoma was the most predominant histologic type (85.3%). BLV, EBV and HPV were detected in (22.7% vs. 16%, 14.7% vs. 8%, 6.7% vs. 0%) BC vs. non-BC tissues respectively with HR HPV 16 detection. Lymphovascular invasion (LVI) and stage III were more commonly seen among tissues with positive viral detection vs. those which were negative (64.3% vs. 53% and 39% vs. 17% respectively). However, no single viral detection was found to be statistically significant in relation to clinicopathological parameters. Multiple viral co-existence was found in 18% of PCR positive cases which was significantly associated with younger age (P = 0.026).

Conclusion: Low rate of viral presence was found in BC tissues. Nevertheless, LVI and stage III were more commonly seen in tissues with positive viral detection. Moreover, a synergetic relation between multiple viral existence and BC development in young age could be possible yet to be verified.

One of the hallmarks of lung cancers is the earlier metastasis resulting from the dissemination of cancer cells. Although accumulating evidence suggests that bacterial infection may be involved in the development of the metastasis of lung cancer, few studies have explored the molecular mechanisms of bacterial infection in the dissemination of lung cancer cells. A series of studies have indicated that certain Gram-negative bacteria are able to hijack antigen-presenting cells (APCs) via interaction with DC-SIGN (CD209) receptors to facilitate the dissemination of pathogens, including viruses, bacteria, fungi, and parasites. Therefore, in the present work, it was hypothesized that bacterial infection may promote the dissemination of cancer cells via the utilization of a similar mechanism. It was first discovered that human lung cancer tissues contain a very high diversity of bacterial DNAs, indicating the co-existence of lung cancer tissues and microbial organisms. It was then found that lung cancer tissues express DC-SIGN, leading to binding with a Gram-negative bacterium, Shigella sonnei. Further, this bacterium was found to be able not only to induce the expression of DC-SIGN on macrophages but also to enhance the migration ability of lung cancer cells in vitro. The in vivo experiments supported these observations, showing that in wild-type (WT) mice, Shigella sonnei infection significantly increased tumor size, weight, and metastatic nodules compared to SIGNR1 knockout (KO) mice. These observations were associated with increasing DC-SIGN expression in WT mice. Finally, these results suggest that bacterial infections could play a significant role in promoting lung cancer progression and metastasis via DC-SIGN-mediated mechanisms.

Objective: Bladder cancer (BCa) has become a growing concern worldwide, highlighting the importance of early detection and new treatment methods. Recent studies have shown that viruses from the HERV family play a significant role in the development of various cancers and can act as early diagnostic biomarkers. Although hypomethylation of HERV-K has been proven in bladder cancer, no studies have yet explored the role of HERV-K oncogenes such as env, gag, np9, and rec. In this study, for the first time, we investigate the expression of these genes and their relationship with each other, aiming to shed light on their potential role in bladder cancer progression and diagnosis.

Methods and materials: We collected a total of 42 samples, comprising 21 bladder transitional cell carcinoma (TCC) samples and 21 adjacent normal tissue samples. Following RNA extraction, the expression levels of HERV-K (HML-2) genes (env, gag, np9, and rec) were evaluated using quantitative real-time PCR (qRT-PCR). For statistical analysis, GraphPad software was employed, utilizing the Kruskal-Wallis test, Mann-Whitney U test, and correlation tests to assess the data.

Results: We found that env and np9 were significantly upregulated in BCa tissues compared to normal tissues (p < 0.0001 and p = 0.022, respectively). While env showed strong associations with tumor grade (low-grade: p = 0.0006; high-grade: p = 0.0011) and stage (early stage: p = 0.0002; invasive stage: p = 0.0047), np9 exhibited consistent associations across all grades (low-grade: p = 0.017; high-grade: p = 0.042) but was exclusively linked to invasive stages (p = 0.001). Although gag expression did not differ significantly overall, it was elevated in the invasive stages of tumors (p = 0.0021). Interestingly, while rec expression showed an increase in cancerous tissues compared to normal tissues, this change was not statistically significant. However, it exhibited significant correlations with other HERV-K genes in cancerous tissue (r = 0.63, p < 0.0001 with env; r = 0.80, p < 0.0001 with gag; and r = 0.39, p = 0.015 with np9). Age-stratified analysis revealed tumor-specific env (p = 0.0272) and rec (p = 0.0017) variations, whereas normal tissues showed only marginal rec age-dependence (p = 0.0494).

Conclusion: The results of our study highlight the potential role of HERV-K genes, particularly env and np9, in BCa progression and demonstrate their promising utility as diagnostic biomarkers.

Background: Kaposi sarcoma (KS) is a cancer of viral origin (Kaposi sarcoma-associated herpesvirus; KSHV) for which the detection of KSHV DNA is an attractive target for a rapid, automatable diagnostic test. We previously demonstrated favorable diagnostic accuracy using loop-mediated isothermal amplification (LAMP) to quantitate KSHV DNA in lesional skin biopsies, though extracting DNA from the punch biopsies was the time-limiting step. Herein, we describe the development of a biopsy processing tool called Slicer to enable rapid nucleic acid testing in addition to traditional histopathological interpretation.

Methods: Slicer divides skin punch biopsies into two ½-cylinders and a thin, cross-sectional slice. The thin slice enables a previously demonstrated, equipment-free alkaline extraction termed ColdSHOT while the remaining ½-cylinders are available for histopathological diagnosis and additional molecular testing as needed. Slicer prototypes were used on skin punch biopsies collected from patients in Uganda who were referred for clinical suspicion of KS.

Results: For 27 patient samples, the combination of Slicer and ColdSHOT sample processing with LAMP testing resulted in qualitative KSHV DNA detection that was fully concordant with US-based histopathological diagnoses. Additional analysis demonstrated compatibility of Slicer and ColdSHOT with qPCR for KSHV DNA quantitation.

Conclusions: These results warrant further investigation using a larger set of skin biopsies and indicate that the Slicer and ColdSHOT could enable accurate KS diagnosis within a few hours of biopsy collection with minimal equipment.

Mendelian Randomization (MR) is increasingly used in cancer research to infer causal relationships by leveraging genetic variants as instrumental variables. While the growth of genome-wide association studies and biobank data has expanded the utility of MR, this surge-particularly pronounced in China-raises concerns about methodological rigor. The widespread adoption may be partly driven by the Chinese translation of key MR literature. Recent advances such as multivariable MR, mediation analysis, and integration with AI and omics data have enhanced the robustness and biological interpretability of MR studies. However, challenges persist, including horizontal pleiotropy, weak instrument bias, and misinterpretation of biomarkers as causal exposures. To improve MR study credibility, frameworks like STROBE-MR and MR-GRADE are being adopted. This article reviews methodological improvements and persistent pitfalls in MR, especially within cancer epidemiology, and highlights strategies for ensuring validity in this rapidly evolving field.

Cervical cancer (CC) is a common cancer that causes considerable morbidity and mortality, especially in developing countries. Bone marrow stromal cell antigen 2 (BST2) is a transmembrane glycoprotein, and its promoter methylation has been extensively documented in numerous human cancers. Nevertheless, the specific role of BST2 in CC remains unclear. This research utilized methylation-specific PCR (MSP), Western blotting, and RT-qPCR to evaluate the expression and DNA methylation levels of BST2 in CC tissues and cells. The role of STAT1 in regulating BST2 transcription was confirmed through dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays. Furthermore, we conducted experiments on cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and xenograft tumor models to investigate the functional role and regulatory mechanisms of BST2 in CC, both in vitro and in vivo. We found that BST2 was increased in CC tissues and cells, promoting cell proliferation and EMT while inhibiting apoptosis. Mechanistically, BST2 upregulation was associated with hypomethylation of its promoter, potentially regulated by DNMT3a and DNMT3b. Furthermore, the transcription factor STAT1 was found to bind to the BST2 promoter, positively regulating its expression and thereby accelerating tumorigenesis in CC. Silencing BST2 significantly reduced tumor growth in vivo. Our findings highlight BST2 as a potential biomarker and therapeutic target in CC, with its expression regulated by DNA methylation and STAT1 binding.

Background: The aim of this study was to investigate the effect of inconsistent expression of p16 and HPV on the prognosis of patients with Oropharyngeal squamous cell carcinoma (OPSCC) in Chinese/Asian populations.

Methods: The study included 130 patients. Inclusion criteria were primary OPSCC. The primary outcome was the proportion of cohort patients showing different combinations of p16 and HPV outcomes, as well as overall survival (OS) and progression-free survival (PFS). Patients with relapsed or metastatic disease or palliative care were excluded from the survival analysis. A multivariate analysis model was used to calculate the adjusted hazard ratio for overall survival for different p16 and HPV tests, adjusted for pre-specified confounders.

Results: Among the 130 patients, 25 (19.2%) demonstrated inconsistency between HPV and p16 expressions. The inconsistency in HPV/p16 status was significantly associated with patient age, smoking history, and alcohol consumption, leading to significant differences in tumor site, TNM staging, and differentiation, thereby influencing treatment decisions. There were significant differences in OS (P = 0.04) and PFS (P = 0.011) among the three groups, with the inconsistent group falling between the HPV+/p16 + group and the HPV-/p16- group but closer to the latter. Out of 54 p16-positive patients, only 33 (61.1%) were HPV-positive, indicating a lower predictive value of p16 for HPV positivity in OPSCC than observed in Western populations. Moreover, the study suggested a potential positive correlation between p16 expression intensity and improved patient prognosis.

Conclusion: In the China/Asia region, where HPV infection rates are relatively low, the predictive power of p16 for HPV-related OPSCC is low. We recommend additional HPV testing in patients with p16 + OPSCC to improve diagnostic accuracy, thereby enabling the selection of the best de-escalation treatment strategy, increasing treatment response rates, and ultimately improving the overall prognosis in these patients.