A comprehensive AI model development framework for consistent Gleason grading.

BACKGROUND: Artificial Intelligence(AI)-based solutions for Gleason grading hold promise for pathologists, while image quality inconsistency, continuous data integration needs, and limited generalizability hinder their adoption and scalability. METHODS: We present a comprehensive digital pathology workflow for AI-assisted Gleason grading. It incorporates A!MagQC (image quality control), A!HistoClouds (cloud-based annotation), Pathologist-AI Interaction (PAI) for continuous model improvement, Trained on Akoya-scanned images only, the model utilizes color augmentation and image appearance migration to address scanner variations. We evaluate it on Whole Slide Images (WSI) from another five scanners and conduct validations with pathologists to assess AI efficacy and PAI. RESULTS: Our model achieves an average F1 score of 0.80 on annotations and 0.71 Quadratic Weighted Kappa on WSIs for Akoya-scanned images. Applying our generalization solution increases the average F1 score for Gleason pattern detection from 0.73 to 0.88 on images from other scanners. The model accelerates Gleason scoring time by 43% while maintaining accuracy. Additionally, PAI improve annotation efficiency by 2.5 times and led to further improvements in model performance. CONCLUSIONS: This pipeline represents a notable advancement in AI-assisted Gleason grading for improved consistency, accuracy, and efficiency. Unlike previous methods limited by scanner specificity, our model achieves outstanding performance across diverse scanners. This improvement paves the way for its seamless integration into clinical workflows.

Gleason grading is a well-accepted diagnostic standard to assess the severity of prostate cancer in patients' tissue samples, based on how abnormal the cells in their prostate tumor look under a microscope. This process can be complex and time-consuming. We explore how artificial intelligence (AI) can help pathologists perform Gleason grading more efficiently and consistently. We build an AI-based system which automatically checks image quality, standardizes the appearance of images from different equipment, learns from pathologists' feedback, and constantly improves model performance. Testing shows that our approach achieves consistent results across different equipment and improves efficiency of the grading process. With further testing and implementation in the clinic, our approach could potentially improve prostate cancer diagnosis and management.

Multi-Instance Multi-Task Learning for Joint Clinical Outcome and Genomic Profile Predictions From the Histopathological Images.

With the remarkable success of digital histopathology and the deep learning technology, many whole-slide pathological images (WSIs) based deep learning models are designed to help pathologists diagnose human cancers. Recently, rather than predicting categorical variables as in cancer diagnosis, several deep learning studies are also proposed to estimate the continuous variables such as the patients' survival or their transcriptional profile. However, most of the existing studies focus on conducting these predicting tasks separately, which overlooks the useful intrinsic correlation among them that can boost the prediction performance of each individual task. In addition, it is sill challenge to design the WSI-based deep learning models, since a WSI is with huge size but annotated with coarse label. In this study, we propose a general multi-instance multi-task learning framework (HistMIMT) for multi-purpose prediction from WSIs. Specifically, we firstly propose a novel multi-instance learning module (TMICS) considering both common and specific task information across different tasks to generate bag representation for each individual task. Then, a soft-mask based fusion module with channel attention (SFCA) is developed to leverage useful information from the related tasks to help improve the prediction performance on target task. We evaluate our method on three cancer cohorts derived from the Cancer Genome Atlas (TCGA). For each cohort, our multi-purpose prediction tasks range from cancer diagnosis, survival prediction and estimating the transcriptional profile of gene TP53. The experimental results demonstrated that HistMIMT can yield better outcome on all clinical prediction tasks than its competitors.

M6A methylation of FKFB3 reduced pyroptosis of gastric cancer by NLRP3.

Gastric cancer is a kind of malignant tumor that seriously endangers human life and health. Its incidence rate and mortality rate are among the highest in the global malignant tumors. Therefore, this study explored the role of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in the progression of gastric cancer and its underlying mechanism. Patients with gastric cancer were collected, and human GC cell lines (stomach gastric carcinoma 7901, stomach gastric carcinoma 823 , human gastric carcinoma cell line 803 and adenocarcinoma gastric stomach) were used in this study. We utilized glucose consumption, cell migration, and ELISA assay kits to investigate the function of GC. To understand its mechanism, we employed quantitative PCR (qPCR), western blot, and m6A methylated RNA immunoprecipitation assay. FKFB3 protein expression levels in patients with gastric cancer were increased. The induction of PFKFB3 mRNA expression levels in patients with gastric cancer or gastric cancer cell lines. Gastric cancer patients with high PFKFB3 expression had a lower survival rate. PFKFB3 high expression possessed the probability of pathological stage, lymph node metastasis or distant metastasis in patients with gastric cancer. PFKFB3 upregulation promoted cancer progression and Warburg effect progression of gastric cancer. PFKFB3 upregulation reduced pyroptosis and suppressed nucleotidebinding domain, leucinerich repeat containing protein 3-induced pyroptosis of gastric cancer. M6A-forming enzyme methyltransferase-like 3 increased PFKFB3 stability. Taken together, the M6A-forming enzyme methyltransferase-like 3 increased PFKFB3 stability and reduced pyroptosis in the model of gastric cancer through the Warburg effect. The PFKFB3 gene represents a potential therapeutic strategy for the treatment of gastric cancer.

Histological diagnosis of unprocessed breast core-needle biopsy via stimulated Raman scattering microscopy and multi-instance learning.

Core-needle biopsy (CNB) plays a vital role in the initial diagnosis of breast cancer. However, the complex tissue processing and global shortage of pathologists have hindered traditional histopathology from timely diagnosis on fresh biopsies. In this work, we developed a full digital platform by integrating label-free stimulated Raman scattering (SRS) microscopy with weakly-supervised learning for rapid and automated cancer diagnosis on un-labelled breast CNB. Methods: We first compared the results of SRS imaging with standard hematoxylin and eosin (H&E) staining on adjacent frozen tissue sections. Then fresh unprocessed biopsy tissues were imaged by SRS to reveal diagnostic histoarchitectures. Next, weakly-supervised learning, i.e., the multi-instance learning (MIL) model was conducted to evaluate the ability to differentiate between benign and malignant cases, and compared with the performance of supervised learning model. Finally, gradient-weighted class activation mapping (Grad-CAM) and semantic segmentation were performed to spatially resolve benign/malignant areas with high efficiency. Results: We verified the ability of SRS in revealing essential histological hallmarks of breast cancer in both thin frozen sections and fresh unprocessed biopsy, generating histoarchitectures well correlated with H&E staining. Moreover, we demonstrated that weakly-supervised MIL model could achieve superior classification performance to supervised learnings, reaching diagnostic accuracy of 95% on 61 biopsy specimens. Furthermore, Grad-CAM allowed the trained MIL model to visualize the histological heterogeneity within the CNB. Conclusion: Our results indicate that MIL-assisted SRS microscopy provides rapid and accurate diagnosis on histologically heterogeneous breast CNB, and could potentially help the subsequent management of patients.

Pacemaker Associated Aspergillus fumigatus Endocarditis: A Case Report.

Aspergillus endocarditis (AE) is a highly fatal infection that can occur in heart valve replacement, pacemaker implantation and other heart surgeries, and early recognition and sufficient diagnosis are challenging. Here, we report the case of a 68-year-old male with a history of dilated cardiomyopathy and pacemaker implantation who had a repeated fever with failed antibacterial treatment and sterile blood culture. He developed endocarditis, and the culture and biopsy of vegetation tissue showed the abundant presence of septate hyphae, which was subsequently identified as Aspergillus fumigatus by internal transcribed spacer (ITS) sequencing. Although the patient had serious side effects from voriconazole, he had a good prognosis following surgery and prolonged caspofungin antifungal therapy of 42 consecutive days. We discuss the diagnosis and treatment strategy of AE, and recommend galactomannan assays and next-generation sequencing for a timely diagnosis. Early surgical intervention combined with prompt antifungal therapy appears significant for survival.

A mucosal recovery software tool for endoscopic submucosal dissection in early gastric cancer.

Background: Due to the limited diagnostic ability, the low detection rate of early gastric cancer (EGC) is a serious health threat. The establishment of the mapping between endoscopic images and pathological images can rapidly improve the diagnostic ability to detect EGC. To expedite the learning process of EGC diagnosis, a mucosal recovery map for the mapping between ESD mucosa specimen and pathological images should be performed in collaboration with endoscopists and pathologists, which is a time-consuming and laborious work. Methods: 20 patients at the Zhejiang Provincial People's Hospital, Affiliated People's Hospital of Hangzhou Medical College from March 2020 to July 2020 were enrolled in this study. We proposed the improved U-Net to obtain WSI-level segmentation results, and the WSI-level results can be mapped to the macroscopic image of the specimen. For the convenient use, a software pipeline named as "Pathology Helper" for integration the workflow of the construction of mucosal recovery maps was developed. Results: The MIoU and Dice of our model can achieve 0.955 ± 0.0936 and 0.961 ± 0.0874 for WSI-level segmentation, respectively. With the help of "Pathology Helper", we can construct the high-quality mucosal recovery maps to reduce the workload of endoscopists and pathologists. Conclusion: "Pathology Helper" will accelerate the learning of endoscopists and pathologists, and rapidly improve their abilities to detect EGC. Our work can also improve the detection rate of early gastric cancer, so that more patients with gastric cancer will be treated in a timely manner.

Artificial intelligence defines protein-based classification of thyroid nodules.

Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort. This classifier achieved over 91% accuracy in the discovery set for classifying malignant thyroid nodules. The classifier was externally validated by blinded analyses in a retrospective cohort of 288 nodules (89% accuracy; FFPE) and a prospective cohort of 294 FNA biopsies (85% accuracy) from twelve independent clinical centers. This study shows that integrating high-throughput proteomics and AI technology in multi-center retrospective and prospective clinical cohorts facilitates precise disease diagnosis which is otherwise difficult to achieve by other methods.

Metabolomics analysis reveals four biomarkers associated with the gouty arthritis progression in patients with sequential stages.

OBJECTIVES: The gouty arthritis (GA) progression was multistage, yet the GA clinical diagnosis guidelines were more inclined to suitable for acute gouty arthritis (AGA), thus neglecting of the progress of GA. This study aimed to identify specific biomarkers that were competent for reflecting the progression of GA and attempted to provide evidence for seasonable intervention of appropriate clinical treatment. METHODS: A total of 547 patients with GA at sequential stages and healthy volunteers were divided into a training set (n = 347) and a validation set (n = 200). Serum metabolic profiles were determined by UHPLC-QTOF-MS-MS untargeted metabolomics, and biomarkers were identified by logistic regression and receiver operating characteristic analysis. Further, UHPLC-QE-MS was applied for accurate quantitative validation of identified potential biomarkers in the validation set samples. RESULTS: After serum metabolic profiles analysis by untargeted metabolomics, 12 metabolites with monotonous change trend were screened, and were verified by targeted metabolomics subsequently. The quantitative results showed the serum concentration of kynurenic acid(KYNA), N1-Methyl-2-pyridone-5-carboxamide(2PY), DL-2-Aminoadipic acid(2AMIA) and 5-hydroxyindole acetic acid(5-HIAA) of patients with sequential stages showed a strictly monotonic trend, and AUC was 0.97, 0.97, 0.96 and 0.95, respectively. CONCLUSIONS: KYNA and 5-HIAA are related to acute inflammation of GA, while 2PY and 2AMIA are related to renal function damage caused by long-term HUA. Therefore, we believe it is inappropriate to use a single biomarker to define the phase of GA. Actually, four biomarkers obtained in this paper should be integratedly adopted to evaluate the progression of GA with sequential stages.

Characteristics and potential malignancy of colorectal juvenile polyps in adults: a single-center retrospective study in China.

BACKGROUND: Colorectal juvenile polyps are rare and generally considered benign in adults. Carcinogenesis or neoplastic changes are rarely mentioned in the literature. We systematically evaluated the characteristics and potential malignancy of colorectal juvenile polyps in adults. METHODS: We retrospectively reviewed the medical records of 103 adults diagnosed with colorectal juvenile polyps from September 2007 to May 2020 at our hospital. The characteristics, endoscopic findings, occurrence of intraepithelial neoplasia, carcinogenesis and diagnostic value of chicken skin mucosa (CSM) were analyzed. RESULTS: The average age of patients with juvenile polyps was 43.2 years (range, 19 to 78 years). A total of 101 patients (101/103, 98.1%) had a single juvenile polyp, and two patients had multiple polyps (107 polyps in total). Polyp sizes ranged from 0.5 to 5 cm. One (1/107, 0.9%) juvenile polyp was cancerous, and 7 (7/107, 6.5%) developed low-grade intraepithelial neoplasia. Neoplasia and cancerization did not appear in the two patients with multiple polyps. A 27-year-old female had a 2-cm polyp with well-differentiated adenocarcinoma in the mucosa in the sigmoid colon with erosion on the surface. CSM was observed adjacent to 17 polyps, which were all located in the rectum and sigmoid colon, and one polyp showed low-grade intraepithelial neoplasia. CONCLUSIONS: Colorectal juvenile polyps occur in a wide range of locations and in variable sizes and numbers. These polyps are solitary in most patients and have neoplastic potential. CSM is not a tumorigenic marker in colorectal juvenile polyps and usually occurs in the distant colorectum. Colorectal juvenile polyps in adults may progress from low-grade intraepithelial neoplasia to high-grade intraepithelial neoplasia and then to carcinoma and should be treated when discovered and regularly followed as colorectal adenomas.

Paradoxical role of interleukin-33/suppressor of tumorigenicity 2 in colorectal carcinogenesis: Progress and therapeutic potential.

Colorectal cancer (CRC) is presently the second most prevalent global mortality-inducing cancer. CRC carcinogenesis is a multifactorial process involving internal genetic mutations and the external environment. In addition, non-neoplastic cell activities within tumor microenvironments for CRC development have been established. However, interleukin (IL)-33, secreted by such cell types, plays a pivotal role in cancer progression due to interaction with cellular constituents within the tumor-inflammation microenvironment. IL-33 belongs to the IL-1 cytokine family and acts as binding attachments for the suppressor of tumorigenicity (ST)2 receptor. Therefore, how to coordinate tumor microenvironment, design and optimize treatment strategies suitable for CRC, based on IL-33/ST2 signal is a challenge. Even though it has established influences upon immunity-linked conditions, IL-33 effects on CRC progression and prevention and related mechanisms are still controversial. Our review depicts controversial activities for IL-33/ST2 within carcinogenesis and cancer prevention. Moreover, IL-33/ST2 signaling is a potential therapeutic target for CRC.

Epidemiology of Drug- and Herb-Induced Liver Injury Assessed for Causality Using the Updated RUCAM in Two Hospitals from China.

Drug- and herb-induced liver injury (DILI and HILI) is an increasingly common and serious condition. Here, data for DILI and HILI patients from two large tertiary hospitals were retrospectively analyzed. Patient characteristics, causes and severity of DILI and HILI, the correlation between expression of p62 and the severity of DILI and HILI, treatment of DILI and HILI, and the prognostic factors of DILI and HILI were studied. A total of 82 patients with DILI and HILI were recruited for the study. Most patients presented with hepatocellular injury, followed by cholestatic injury and mixed injury. Our results indicate that traditional Chinese medicine or herbal and dietary supplements were the prevalent causal agents of HILI, which was characterized by higher frequencies of hepatocellular injury. Expression of p62 in the liver correlated with the severity of DILI and HILI. Improvements in the results of the liver enzymatic tests correlated with alanine transaminase (ALT) levels upon the first diagnosis of DILI and HILI and with the hepatocellular type of DILI and HILI. In conclusion, we provide an epidemiological assessment of DILI and HILI based on causality using the updated RUCAM on patients from two hospitals in China. ALT levels at first diagnosis and the hepatocellular type of injury may be prognostic factors of DILI and HILI.

Establishment of a clinical diagnostic model for gouty arthritis based on the serum biochemical profile: A case-control study.

ABSTRACT: The disease progression of gouty arthritis (GA) is relatively clear, with the 4 stages of hyperuricemia (HUA), acute gouty arthritis (AGA), gouty arthritis during the intermittent period (GIP), and chronic gouty arthritis (CGA). This paper attempts to construct a clinical diagnostic model based on blood routine test data, in order to avoid the need for bursa fluid examination and other tedious steps, and at the same time to predict the development direction of GA.Serum samples from 579 subjects were collected within 3 years in this study and were divided into a training set (n = 379) and validation set (n = 200). After a series of multivariate statistical analyses, the serum biochemical profile was obtained, which could effectively distinguish different stages of GA. A clinical diagnosis model based on the biochemical index of the training set was established to maximize the probability of the stage as a diagnosis, and the serum biochemical data from 200 patients were used for validation.The total area under the curve (AUC) of the clinical diagnostic model was 0.9534, and the AUCs of the 5 models were 0.9814 (Control), 0.9288 (HUA), 0.9752 (AGA), 0.9056 (GIP), and 0.9759 (CGA). The kappa coefficient of the clinical diagnostic model was 0.80.This clinical diagnostic model could be applied clinically and in research to improve the accuracy of the identification of the different stages of GA. Meanwhile, the serum biochemical profile revealed by this study could be used to assist the clinical diagnosis and prediction of GA.

Development and validation of an individualized prediction calculator of postoperative mortality within 6 months after surgical resection for hepatocellular carcinoma: an international multicenter study.

BACKGROUND: Evidence-based decision-making is critical to optimize the benefits and mitigate futility associated with surgery for patients with malignancies. Untreated hepatocellular carcinoma (HCC) has a median survival of only 6 months. The objective was to develop and validate an individualized patient-specific tool to predict preoperatively the benefit of surgery to provide a survival benefit of at least 6 months following resection. METHODS: Using an international multicenter database, patients who underwent curative-intent liver resection for HCC from 2008 to 2017 were identified. Using random assignment, two-thirds of patients were assigned to a training cohort with the remaining one-third assigned to the validation cohort. Independent predictors of postoperative death within 6 months after surgery for HCC were identified and used to construct a nomogram model with a corresponding online calculator. The predictive accuracy of the calculator was assessed using C-index and calibration curves. RESULTS: Independent factors associated with death within 6 months of surgery included age, Child-Pugh grading, portal hypertension, alpha-fetoprotein level, tumor rupture, tumor size, tumor number and gross vascular invasion. A nomogram that incorporated these factors demonstrated excellent calibration and good performance in both the training and validation cohorts (C-indexes: 0.802 and 0.798). The nomogram also performed better than four other commonly-used HCC staging systems (C-indexes: 0.800 vs. 0.542-0.748). CONCLUSIONS: An easy-to-use online prediction calculator was able to identify patients at highest risk of death within 6 months of surgery for HCC. The proposed online calculator may help guide surgical decision-making to avoid futile surgery for patients with HCC.

Multifocal gastrointestinal epithelioid angiosarcomas diagnosed by endoscopic mucosal resection: A case report.

BACKGROUND: Epithelioid angiosarcoma is a vascular neoplasm that is among the most aggressive subtypes of sarcomas. Its involvement in the gastrointestinal tract is rare. We here report a case of multifocal gastrointestinal epithelioid angiosarcomas presenting with gastrointestinal bleeding. CASE SUMMARY: A 77-year-old woman was admitted because of melena and dizziness for three months. Gastroscopy and colonoscopy were performed, revealing a centrally ulcerated hemorrhagic polypoid lesion in the gastric body and multiple polypoid lesions with blood clots and hemorrhagic tendency in the colon. Histopathological examination of routine endoscopic biopsy samples showed inflammation in the gastric mucosa and tubular adenomas in the colon. The polypoid lesions were removed by endoscopic mucosal resection. Immunohistochemistry suggested a final diagnosis of epithelioid angiosarcomas. The patient refused chemotherapy and died after three months. CONCLUSION: Epithelioid angiosarcomas are characterized by highly vascular nature and tendency to cause gastrointestinal bleeding. Efforts to obtain histological findings using endoscopic mucosal resection are of great importance.

Fat mass and obesity-associated protein promotes the tumorigenesis and development of liver cancer.

Liver cancer is the fourth leading cause of cancer-associated mortality worldwide. Statistics indicate that the incidence of liver cancer has been increasing and that its prognosis remains poor. Fat mass and obesity-associated protein (FTO) is a demethylase that is involved in N6-methyladenosine (m6a) RNA modification; however, to the best of our knowledge, its role in tumorigenesis and development of liver cancer remains unknown. In the present study, cell proliferation, colony formation, apoptosis, Transwell and wound healing assays of small interfering (si)RNA-FTO HepG2 cells were performed, and the levels of m6A RNA methylation were assessed. Additionally, the prognostic value of FTO in liver cancer was analyzed using immunohistochemistry analysis. The results from the EpiQuik m6A RNA methylation quantitative assay revealed that knockdown of FTO increased the total m6A methylation level. Notably, FTO promoted the proliferation and migration of liver cancer cells. Additionally, FTO expression was upregulated in patients with liver cancer and was associated with a high Edmondson Grade, which served as an independent prognostic factor for liver cancer. Results from the Kaplan-Meier survival analysis revealed that low expression levels of FTO predicted a good prognosis. The 5-year overall survival of the low FTO expression group was 68% compared with 48% in the high FTO expression group (P=0.077). In conclusion, the present study suggested that FTO regulates the tumorigenesis and development of liver cancer.

Retroperitoneal bronchogenic cyst resembling an adrenal tumor: two case reports and literature review.

Bronchogenic cysts are primitive, foregut-derived developmental anomalies with bronchial-type, pseudostratified cylindrical epithelium. They are usually discovered in the thorax. The occurrence of such cysts in the retroperitoneum is extremely rare. Imaging techniques are generally effective in the detection of retroperitoneal bronchogenic cyst. Here, we report two cases (a 27-year-old man and a 33-year-old man) who had no clinical symptoms and were found by chance to have masses in the adrenal gland area during routine physical examination. We found that they had some similar computed tomography imaging features, including complete adrenal structure, cystic fusiform mass in adrenal region, and inclusion of calcifications in the lesions. However, accurate preoperative diagnosis remains difficult and only histology can provide a definitive diagnosis. Surgery remains the treatment of choice.

Diagnosis and management of a solitary colorectal juvenile polyp in an adult during follow-up for ulcerative colitis: A case report.

BACKGROUND: Juvenile polyps are the most common type of polyps in children but are rare in adults. Inflammatory bowel disease (IBD) patients have a similar spectrum of symptoms as patients with juvenile polyps. Both patients with juvenile polyps and those with active IBD have high fecal calprotectin levels. Four cases of children with ulcerative colitis (UC) with solitary juvenile polyps and one case of an adult with UC with juvenile polyposis syndrome have been reported upon diagnosis of UC, while there have been no cases of adults with UC with solitary juvenile polyp reported in the literature. CASE SUMMARY: A 37-year-old man with a 12-year history of UC was admitted to our clinic because of increased stool frequency. UC was diagnosed at the age of 25. As the lesion was confined to the rectum, sulfasalazine suppositories or mesalazine suppositories were used. The patient was followed in an outpatient clinic, and colonoscopy was performed every one or two years. The latest examination was undertaken three years prior in the presence of proctitis. Recently, the patient complained of three to five bowel movements a day. There was mucus in the stool but no visible blood. Colonoscopy revealed a solitary polyp, about 1.5 cm in diameter, with a short and broad peduncle in the transverse colon surrounded by congestive and edematous mucosa. The patient had no family history of colorectal polyps or cancer. The polyp was successfully removed by endoscopic mucosal resection. Histopathological examination revealed that the polyp was a juvenile polyp without any malignant signs. Immunohistochemical staining for p53 showed wild-type expression and p53 overexpression was not detected. Ki-67 labeling index was 3%. CONCLUSION: This is the first case of an adult UC patient with a solitary juvenile polyp at the 12-year follow-up. The correlation between juvenile polyps and the activity of IBD needs further study.

The lncRNA PVT1 regulates nasopharyngeal carcinoma cell proliferation via activating the KAT2A acetyltransferase and stabilizing HIF-1α.

Long noncoding RNAs (lncRNAs) play important roles in regulating the development and progression of many cancers. However, the clinical significance of specific lncRNAs in the context of nasopharyngeal carcinoma (NPC) and the molecular mechanisms by which they regulate this form of cancer remain largely unclear. In this study we found that the lncRNA PVT1 was upregulated in NPC, and that in patients this upregulation was associated with reduced survival. RNA sequencing revealed that PVT1 was responsible for regulating NPC cell proliferation and for controlling a hypoxia-related phenotype in these cells. PVT1 knockdown reduced NPC cell proliferation, colony formation, and tumorigenesis in a subcutaneous mouse xenograft model systems. We further found that PVT1 serves as a scaffold for the chromatin modification factor KAT2A, which mediates histone 3 lysine 9 acetylation (H3K9), recruiting the nuclear receptor binding protein TIF1ß to activate NF90 transcription, thereby increasing HIF-1α stability and promoting a malignant phenotype in NPC cells. Overexpression of NF90 or HIF-1α restored the proliferation in cells that had ceased proliferating due to PVT1 or KAT2A depletion. Conversely, overexpression of active KAT2A or TIF1ß, but not of KAT2A acetyltransferase activity-deficient mutants or TIF1ß isoforms lacking H3K9ac binding sites, promoted a PVT1-mediated increase in NF90 transcription, as well as increased HIF-1α stability and cell proliferation. PVT1 knockdown enhanced the radiosensitization effect in NPC cells via inhibiting binding between H3K9ac and TIF1ß in a manner. Taken together, our results demonstrate that PVT1 serves an oncogenic role and plays an important role in radiosensitivity in malignant NPC via activating the KAT2A acetyltransferase and stabilizing HIF-1α.