Nasopharyngeal carcinoma（NPC） is a distinct type of head and neck cancer closely associated with Epstein-Barr virus（EBV） infection and exhibits significant geographic variations in its incidence. Despite recent advancements in radiotherapy techniques and precision medicine for NPC, the overall survival rate remains unsatisfactory due to tumor metastasis, recurrence, and drug resistance. Single-cell RNA sequencing（scRNA-seq） is an emerging technology that allows for the analysis of gene expression at single-cell resolution, providing a clearer understanding of tumor cell subpopulations, the evolutionary trajectory of tumor cells, and the functional roles and interactions of cells within the tumor microenvironment. This provides new ideas for the development of precision medicine in NPC. Here, we review the applications of scRNA-seq in exploring the mechanisms of NPC pathogenesis, tumor heterogeneity, the tumor microenvironment, drug resistance, and therapeutic response.
Humans ; Nasopharyngeal Neoplasms/genetics* ; Tumor Microenvironment ; Nasopharyngeal Carcinoma ; Single-Cell Analysis ; Sequence Analysis, RNA ; Precision Medicine ; Drug Resistance, Neoplasm ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Single-Cell Gene Expression Analysis

Humans ; Herpesvirus 4, Human ; Wiskott-Aldrich Syndrome ; Epstein-Barr Virus Infections/complications* ; Smooth Muscle Tumor/therapy* ; Hematopoietic Stem Cell Transplantation

Objective To study the pathological types,expression of mismatch repair protein,human epidermal growth factor receptor 2(HER2),and Pan-TRK,and Epstein-Barr virus(EBV)infection in patients with colorectal cancer resected in Tibet. Methods A total of 79 patients with colorectal cancer resected in Tibet Autonomous Region People's Hospital from December 2013 to July 2021 were enrolled in this study.The clinical and pathological data of the patients were collected.The expression of mismatch repair protein,HER2,and Pan-TRK was detected by immunohistochemical(IHC)staining,and detection of HER2 gene by fluorescence in situ hybridization(FISH)in the patients with HER2 IHC results of 2+ or above.EBV was detected by in situ hybridization with EBV-encoded small RNA. Results A total of 79 colorectal cancer patients were included in this study,with the male-to-female ratio of 1.26:1 and the mean age of(57.06±12.74)years(24-83 years).Among them,4 patients received preoperative neoadjuvant therapy.Colonic cancer and rectal cancer occurred in 57(57/79,72.15%,including 31 and 26 in the right colon and left colon,respectively)and 22(22/79,27.85%)patients,respectively.The maximum diameter of tumor varied within the range of 1-20 cm,with the mean of(6.61±3.33)cm.Among the 79 colorectal cancer patients,75(75/79,94.94%)patients showed adenocarcinoma.Lymph node metastasis occurred in 12(12/21,57.14%)out of the 21 patients with severe tumor budding,13(13/23,56.52%)out of the 23 patients with moderate tumor budding,and 2(2/31,6.45%)out of the 31 patients with mild tumor budding,respectively.The lymph node metastasis rate showed differences between the patients with severe/moderate tumor budding and the patients with mild tumor budding(all P<0.001).The IHC staining showed that mismatch repair protein was negative in 10(10/65,15.38%)patients,including 5 patients with both MSH2 and MSH6 negative,4 patients with both MLH1 and PMS2 negative,and 1 patient with MSH6 negative.Pan-TRK was negative in 65 patients.The IHC results of HER2 showed 0 or 1+ in 60 patients and 2+ in 5 patients.FISH showed no positive signal in the 5 patients with HER2 IHC results of 2+.The detection with EBV-encoded small RNA showed positive result in 1(1/65,1.54%)patient. Conclusions Non-specific adenocarcinoma of the right colon is the most common in the patients with colorectal cancer resected in Tibet,and 15% of the patients showed mismatch repair protein defects.EBV-associated colorectal carcer is rare,Pan-TRK expression and HER2 gene amplification are seldom.The colorectal cancer patients with moderate and severe tumor budding are more likely to have lymph node metastasis.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Adenocarcinoma ; Biomarkers, Tumor/genetics* ; Colorectal Neoplasms/pathology* ; DNA Mismatch Repair ; DNA-Binding Proteins/genetics* ; Epstein-Barr Virus Infections/diagnosis* ; Herpesvirus 4, Human/metabolism* ; In Situ Hybridization, Fluorescence ; Lymphatic Metastasis ; Tibet ; Young Adult ; Aged, 80 and over

A girl, aged 7 years, was admitted due to pain in both lower limbs for more than one year. Lumbar MRI showed soft tissue masses in the paravertebral region. Cerebral MRI showed nodular masses in the cavernous sinus at both sides. Chest CT showed high-density nodules in the outer basal segment of the right inferior lobe and the anterior segment of the left upper lobe of the lung. Biopsy of lumbar lesions showed Epstein-Barr (EB) virus-related smooth muscle tumor. Genetic testing showed a
Epstein-Barr Virus Infections ; Female ; Herpesvirus 4, Human/genetics* ; Humans ; Magnetic Resonance Imaging ; Smooth Muscle Tumor/diagnosis* ; Tomography, X-Ray Computed

OBJECTIVE: To investigate the effect of exosomes derived from Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) cells on lymphangiogenesis and lymph node metastasis of NPC. METHODS: Exosomes from NP69 cells and EBV-positive HK1 (HK1-EBV) cells were obtained by ultracentrifugation and identified by Western blotting and nanoparticle tracking analysis. Dio dye phagocytosis test was performed to observe exosome uptake by lymphatic endothelial cells. Lymphatic endothelial cells were treated with exosomes from nasopharyngeal epithelium (NP69), HK1-EBV, and C666-1 cells or exosome-free supernatant of HK1-EBV and C666-1 cells, and tube formation and migration of the cells were observed. In a nude mouse model of popliteal lymph node metastasis of NPC, the effects of normal saline, NP69 cell-derived exosomes, HK1-EBV cell-derived exosomes, exosome-free supernatant of HK1-EBV cells, and HK1-EBV exosome-free supernatant protein on lymphangiogenesis and lymph node metastasis of the tumor were observed. RESULTS: The exosomes obtained by ultracentrifugation contained abundant exosome-specific proteins and showed a normal size range. The exosomes from NPC cells and NP69 cells could be taken up by lymphatic endothelial cells. Compared with the blank control and exosomes form NP69 cells, exosomes derived from HK1-EBV and C666-1 cells significantly promoted tube formation and migration of lymphatic endothelial cells ( CONCLUSIONS Exosomes from EBV-positive NPC cells can significantly promote lymphangiogenesis and lymph node metastasis of NPC.
Animals ; Cell Line, Tumor ; Endothelial Cells ; Epstein-Barr Virus Infections ; Exosomes ; Herpesvirus 4, Human ; Humans ; Lymphangiogenesis ; Lymphatic Metastasis ; Mice ; Mice, Nude ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms

OBJECTIVE: To analyze the correlation of EBV infection with expression of TNF-α-inducing protein 3 gene and A20 protein in Hodgkin lmphoma. METHODS: The clinical data and pathological specimens of 65 cases of Hodgkin's lymphoma in our hospital were analyzed retrospectively, and the tissue chips were made for the rich area of the tumor cells. The latent membrane protein 1 encoded by EBV was measured by immunohistochemical staining, and the RNA encoded by EBV was measured by in situ hybridization to analyze the infection state. The gene expression of tumor necrosis factor.α-induced protein 3 was detected by fluorescence in situ hybridization, and the expression of A20 protein encoded by EBV was detected by immunohistochemical staining. The obtained data were processed by SPSS 23.0 version statistical software. RESULTS: The positive rate of latent membrane protein 1 was 26.15% (17/65), the positive rate of EBV encoded RNA was 26.15% (17/65), and the coincidence rate was 100.00%. In 65 patients, A20 protein expression was lost in 18 cases (27.69%), and 14 cases (21.54%) showed homozygous or heterozygous deletion of tumor necrosis factorα protein 3 gene. Only 1 case showed A20 loss combined with homozygous deletion of TNFα inducible protein 3. Correlation analysis showed that EBV infection did not significantly relate with expression loss of A20 protein and the gene deletion of TNF-α inducing protein 3 (P>0.05). CONCLUSION The expression loss of A20 protein and gene detection of TNFα inducing protein 3 are found in both EBV negative and positive patients with Hodgkin's lymphoma, however the results of immunohistochemical staining and fluorescence in situ hybridization are not complete consistant, the reason may closely relate with the technical factors.
Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Hodgkin Disease ; Humans ; In Situ Hybridization ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Tumor Necrosis Factor alpha-Induced Protein 3 ; genetics ; Viral Matrix Proteins

OBJECTIVE: To analyze the characteristics of BK polymavirus (BKV) infection and the optimal time window for intervention in kidney transplant recipients (KTRs). METHODS: We retrospectively analyzed the clinical data and treatment regimens in 226 KTRs in our center between January, 2013 and January, 2018. Among the recipients, 157 had a urine BKV load ≥1.0×10 copy/mL after transplantation, and 69 had a urine BKV load below 1.0×10 copy/mL (control group). RESULTS: Among the 157 KTRs, 60 (38.2%) recipients were positive for urine BKV, 66 (42.0%) had BKV viruria, and 31(19.7%) had BKV viremia. The incidence of positive urine occult blood was significantly higher in BKV-positive recipients than in the control group ( < 0.05). The change of urine BKV load was linearly related to that of Tacrolimus trough blood level (=0.351, < 0.05). In urine BKV positive group, the average estimated glomerular filtration rate (eGFR) was below the baseline level (60 mL·min·1.73 m) upon diagnosis of BKV infection reactivation, and recovered the normal level after intervention. In patients with BKV viruria and viremia, the average eGFR failed to return to the baseline level in spite of improvement of the renal function after intervention. CONCLUSIONS Positive urine occult blood after transplantation may be associated with BKV infection reactivation in some of the KTRs. BKV infection is sensitive to changes of plasma concentration of immunosuppressive agents. Early intervention of BKV replication in KTRs with appropriate dose reduction for immunosuppression can help to control virus replication and stabilize the allograft function.
BK Virus ; physiology ; Humans ; Kidney Transplantation ; Polyomavirus Infections ; virology ; Retrospective Studies ; Transplant Recipients ; Tumor Virus Infections ; virology ; Viral Load ; Virus Replication

BK virus infection is one of the common complications after hematopoietic stem cell transplantation(HSCT), which is also one of the reasons of the hemorrhagic cystitis．In recent years, although there are more studies of the risk factors related with human BK virus infection after hematopoietic stem cell transplantation, the risk factors related with BKV-associated hemorrhagio cystitis(BKV-HC) remain to be elucidated. Diagnosis of BK virus infection is mainly based on quantitative PCR of blood or urine. An effective strategy for treatment of these patients is the adoptive transfer of T lymphocytes specific to virus-associated antigens. In this review, the progressis of diagnosis and treatment of BK virus infection after hematopoietic stem cell transplantation are briefly summarized.
BK Virus ; Cystitis ; Hematopoietic Stem Cell Transplantation ; Humans ; Polyomavirus Infections ; Tumor Virus Infections

Viral infections cause at least 10%-15% of all human carcinomas. Over the last century, the elucidation of viral oncogenic roles in many cancer types has provided fundamental knowledge on carcinogenetic mechanisms and established a basis for the early intervention of virus-related cancers. Meanwhile, rapidly evolving genome-editing techniques targeting viral DNA/RNA have emerged as novel therapeutic strategies for treating virus-related carcinogenesis and have begun showing promising results. This review discusses the recent advances of genome-editing tools for treating tumorigenic viruses and their corresponding cancers, the challenges that must be overcome before clinically applying such genome-editing technologies, and more importantly, the potential solutions to these challenges.
Antiviral Agents ; therapeutic use ; CRISPR-Cas Systems ; Carcinoma ; genetics ; therapy ; virology ; Gene Editing ; Genetic Predisposition to Disease ; Genetic Therapy ; methods ; Humans ; Tumor Virus Infections ; complications

This study assessed the expression of the p53 protein, beta-catenin, and HER2 and their prognostic implications in patients with EBV-associated gastric cancer (EBVaGC). After reviewing 1318 consecutive cases of surgically resected or endoscopic submucosal dissected gastric cancers, 117 patients were identified as EBV-positive using EBV-encoded RNA in-situ hybridization. The immunohistochemistry results were interpreted as follows: strong p53 nuclear expression in at least 50% of tumor nuclei was interpreted as a positive result, strong beta-catenin expression in at least 10% of cytoplasmic nuclei was interpreted as a positive result, and moderate or strong complete or basolateral membrane staining in 10% of tumor cells was interpreted as a positive result for HER2. Immunohistochemical staining for p53 was performed on tumor tissue from 105 patients, among whom 25 (23.8%) tested positive. Meanwhile, beta-catenin expression was positive in 10 patients (17.5%) and HER2 expression was positive in 8 patients (6.8%). The positive expression of p53 was significantly associated with a high T stage (p=0.006). More patients with lymph node metastasis were p53-positive (p=0.013). In the univariate analysis, the p53-positive patients showed significantly decreased disease-free survival (DFS) when compared with the p53-negative patients (p=0.022), although the p53 status was only marginally associated with overall survival (OS) (p=0.080). However, p53 expression showed no prognostic significance on DFS in the multivariate analysis. Moreover, beta-catenin and HER2 showed no association with DFS and OS in the survival analysis. The current study found a significant correlation between p53 expression and tumor progression and lymph node metastases in patients with EBVaGC.
beta Catenin ; Cytoplasm ; Disease-Free Survival ; Epstein-Barr Virus Infections ; Humans ; Immunohistochemistry ; Lymph Nodes ; Membranes ; Multivariate Analysis ; Neoplasm Metastasis ; RNA ; Stomach Neoplasms ; Tumor Suppressor Protein p53