Malignant Transformation Research Articles

Advances in Understanding Drug Resistance Mechanisms and Innovative Clinical Treatments for Melanoma.

Melanoma, a highly invasive skin cancer resulting from melanocyte malignant transformation, is the third most common skin malignancy. Despite accounting for only 4% to 5% of all skin malignancies, it is responsible for 80% of skin cancer-related deaths. Targeted therapies and immune checkpoint inhibitors have improved survival rates, yet drug resistance remains a major challenge. In this review, I explore the latest research progress on melanoma drug resistance mechanisms and clinical treatment methods. This aims to provide insights for more effective treatment strategies and improve patient prognosis and quality of life. I also discuss potential strategies to overcome drug resistance based on the latest scientific findings, with a particular focus on the complex and multi-factorial drug resistance mechanisms of melanomas, including genetic mutations, epigenetic changes, and tumor microenvironment factors. Understanding these mechanisms is crucial for developing new drugs and combination therapies targeting drug-resistant tumors. Analyzing complex drug resistance pathways paves the way for personalized medical approaches, which is expected to provide enlightenment on breaking through drug resistance barriers and enhancing the effectiveness of melanoma treatment.

Subchronic Exposure to Low-Level Lanthanum, Cerium, and Yttrium Mixtures Altered Cell Cycle and Increased Oxidative Stress Pathways in Human LO-2 Hepatocytes but Did Not Cause Malignant Transformation.

Human exposures to rare earth elements are increasing with expanded use in aerospace, precision instruments, and new energy batteries, materials, and fertilizers. Individually these elements have low toxicity, although few investigations have examined the health effects of longer-term mixture exposures. We used the LO-2 cell line to examine the effects of graded exposures to lanthanum, cerium, and yttrium (LCY) mixtures at 1-, 100-, and 1000-fold their human background levels (0.31 μg/L La, 0.25 μg/L Ce, and 0.12 μg/L Y) on cell cycle, oxidative stress, and nuclear factor erythroid-2-related factor (NRF2) pathway biomarkers, assessing responses every 10 passages up to 100 passages. Cell migration, concanavalin A, malignant transformation, and tumorigenesis in nude mice were also examined. Mixed LCY exposures activated oxidative stress and the NRF2 pathway by the 30th passage and increased the proportion of cells in the S phase and cell cycle-specific biomarkers by the 40th passage. LCY exposures did not cause malignant transformation of hepatocytes or induced tumorigenesis in nude mice but enhanced cell proliferation, migration, and agglutination. Importantly, LCY mixtures with longer-term exposure activated the NRF2 pathway and altered the hepatocyte cell cycle at doses far below those used in previous toxicological studies. The consequences of LCY mixtures for public health merit further study.

Molecular characterization of ovarian squamous cell carcinoma originating from mature teratoma.

Squamous cell carcinoma (SCC) of the ovary, an uncommon form of gynecologic cancer, typically originates from the malignant transformation of a pre-existing mature ovarian teratoma (MOT). However, due to its rarity, the molecular pathways driving its development are not well understood. To address this knowledge gap, we performed molecular inversion probe (MIP) array analysis and targeted sequencing of 275 cancer susceptibility genes on 11 ovarian SCC samples derived from MOTs. Additionally, we conducted the same molecular tests on two samples of ovarian metastases of SCCs that originated from primary sites outside the ovary, specifically, one from endometrial cancer and one from cervical SCC. Utilizing MIP arrays, we identified failures in meiosis I and II, as well as instances of endoreduplication within haploid ova, in five, two, and four samples of ovarian SCCs arising from MOTs, respectively. Notably, such alterations were absent in samples of ovarian metastases, implying that primary ovarian SCCs may derive from teratoma cells. Targeted sequencing identified TP53 as the most frequently mutated gene in ovarian SCCs, occurring in 82% of cases. This was followed by mutations in PIK3CA (36%), PTEN (27%), and KMT2D (27%). Furthermore, mutations in CDKN2A and copy number loss of 9p21.3 were observed in 54.5% of the cohort. In summary, our study elucidates the germ cell origin of ovarian SCC and provides a comprehensive analysis of its genomic landscape, which may assist in differential diagnosis and inform the development of targeted therapies with potential clinical benefits. KEY MESSAGES: Failures in meiosis I/II and endoreduplication found in primary ovarian SCCs. Ovarian SCCs may derive from germ cells in mature teratomas. Alterations absent in ovarian metastases from SCC aid differential diagnosis. TP53 mutations found in 82% of ovarian SCC cases. CDKN2A mutations and 9p21.3 loss observed in 54.5% of ovarian SCC cohort.

Human Papillomavirus Genotype Attribution and Integration in High-Grade Vaginal Intraepithelial Neoplasia

Objective The aim of the study was to investigate the distribution and association between human papillomavirus (HPV) genotypes and integration as well as their correlation with cervical lesions. Methods Two hundred seven patients diagnosed with high-grade vaginal intraepithelial neoplasia (HG-VaIN) were recruited from the Women's Hospital School of Medicine Zhejiang University between 2015 and 2021 and assayed for HPV genotyping. HPV integration sequencing analysis was conducted using tissues from 53 patients with HG-VaIN and 4 patients with invasive vaginal carcinoma (IVC), along with paired cervical lesion specimens. Results A total of 207 patients with HG-VaIN were categorized as having cervical lesions unrelated to HG-VaIN (group A, 71 patients, 34.30%) or cervical lesion-related HG-VaIN (group B, 136 patients, 65.70%). With an average follow-up of 42.19 months, 12 of 153 patients progressed to IVC and were all from group B. HPV16 infection and the presence of cervical lesions were the 2 main factors associated with disease progression, with cervical lesion coexistence being an independent factor. Compared with group A (5/20, 25%), group B (17/33, 51.52%) showed a higher rate of HPV integration, as demonstrated using HPV integration sequencing analysis, with HPV16 being the most integrated genotype (72.73%). The integration analysis of 4 patients with IVC paired with cervical lesion specimens showed that 3 of the 4 pairs exhibited the same HPV infection and integration sites, indicating a high degree of homology in HPV integration between cervical lesions and HG-VaIN-induced IVC. Conclusions Patients with HG-VaIN associated with cervical lesions exhibited a higher risk of malignant transformation, necessitating more proactive treatment approaches.

Development of a novel gene expression panel for the characterization of MSCs for increased biological safety.

Mesenchymal stromal cells (MSCs) have a wide range of therapeutic applications due to their multipotency, immunomodulatory, and anti-inflammatory properties. Their ability to migrate and recolonize damaged tissues is also remarkable. However, the controversial occurrence of spontaneous tumorigenesis or malignant transformation of MSCs raises concerns about proposed cell-based therapies for patients that researchers must address. There are several in vitro and in vivo strategies for MSC safety approval, but there is still no described coherent scheme that allows the assessment of MSC oncogenic potential in a simple, robust, and reproducible manner. Here, we have developed a diagnostic panel of molecular markers that allows for the accurate verification of the quality and safety of MSCs. Moreover, presented in this article diagnostic panel that can define the origin and tumorigenicity of MSCs can be easily introduced into the routine quality control processes of MSC-based product manufacturing which will improve further clinical applications of MSCs.

Postmenopausal Endometriosis: Clinical Insights and Imaging Considerations.

Endometriosis is a chronic systemic condition characterized by the presence of ectopic endometrial-like tissue outside of the uterus. It occurs most often in reproductive-aged patients and less frequently in postmenopausal women. In postmenopausal patients, endometriosis is more common in those undergoing hormone replacement therapy or taking tamoxifen. The risk of malignant transformation of endometriosis is higher in this older population, especially in those undergoing estrogen-only hormone replacement therapy. Many theories on the postmenopausal pathogenesis of endometriosis have been proposed, ranging from reactivation of premenopausal disease to de novo manifestation. Compared with premenopausal disease, postmenopausal endometriosis is typically less active and extensive, with fewer hemorrhagic components. Patients may be symptomatic, with chronic pelvic pain, or may receive the diagnosis after imaging performed for other indications such as an incidental ovarian lesion. Treatment is typically surgical resection or estrogen-blocking medications. Although the diagnosis requires pathologic confirmation, radiologists play an important role in diagnosing both benign endometriosis and malignant transformation. Pelvic US following a dedicated protocol is an accessible screening tool, with high sensitivity for diagnosis of bowel-invasive disease. MRI has better anatomic resolution and allows simultaneous characterization of adnexal and extrapelvic lesions, thereby providing excellent assessment for malignant transformation.

Therapeutic Strategies in Neurocutaneous Melanocytosis.

Neurocutaneous melanocytosis (NCM) is a rare, congenital condition primarily affecting children, characterized by large or giant congenital melanocytic nevi (L/GCMN) on the skin and pigmented lesions in the brain. The presence of pigmented lesions in the brain often leads to neurological symptoms like headaches, seizures, and hydrocephalus, typically manifesting before age two. Melanocytic lesions in the brain can range from benign melanocytosis to malignant melanoma. NCM is nearly always fatal if symptomatic, with a high risk of malignant transformation. Patients with larger skin nevi with neurological involvement tend to have a greater lifetime risk of malignancy. There is no specific treatment, and current therapies focus on palliative care, including surgery, radiation, and chemotherapy. Malignant transformation into melanoma requires aggressive treatments like surgery, radiation, and chemotherapy. Despite these approaches, outcomes remain poor, with no definitive cure for NCM. This study aims to review and critically evaluate the current therapeutic strategies for NCM while also exploring prospective avenues for developing specific and effective treatments. It aims to highlight recent advancements in the molecular understanding of NCM and examine how these insights may inform the development of novel therapeutic approaches. Additionally, the study will address the significant unmet medical needs associated with this rare and often fatal condition, emphasizing the importance of continued research and innovation in its management.

Halobenzoquinone-induced potential carcinogenicity associated with p53-mediated cell cycle pathway

2,6-Dibromo-1,4-benzoquinone (2,6-DBBQ) and 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), two emerging halobenzoquinones (HBQs), have the highest detection frequencies and levels in drinking water among all HBQs. They are more toxic than the regulated disinfection byproducts. Quantitative structure toxicity relationship analysis predicted that HBQs are a class of potential bladder carcinogens. However, direct experimental evidence for the carcinogenicity of 2,6-DBBQ and 2,6-DCBQ is lacking and the associated toxicity mechanisms remain unclear. In this study, we confirmed the potential carcinogenicity of 2,6-DBBQ and 2,6-DCBQ using an in vitro malignant transformation assay, evaluated their cytotoxicity and genotoxicity, and investigated their toxicity mechanisms. The results showed that 2,6-DBBQ and 2,6-DCBQ significantly decreased the viability of human uroepithelial SV-HUC-1 cells and induced DNA damage in SV-HUC-1 cells, and chromosomal damage in HepG2 cells, and malignant transformation of SV-HUC-1 cells. Moreover, transcriptome sequencing revealed that 2,6-DBBQ and 2,6-DCBQ activated the p53-mediated cell cycle pathway in bladder cancer. In the p53-mediated cell cycle pathway, 2,6-DBBQ and 2,6-DCBQ induced cell cycle arrest at the S phase by downregulating p53 and upregulating p21. Additionally, 2,6-DBBQ and 2,6-DCBQ may have produced excessive reactive oxygen species, damaging DNA and chromosomes. These results not only first confirm the potential carcinogenicity of 2,6-DBBQ and 2,6-DCBQ but also provide an important reference for exploring the cytotoxicity and genotoxicity mechanisms of these HBQs.

Dental pulp stem cells promote malignant transformation of oral epithelial cells through mitochondrial transfer.

Oral epithelial dysplasia includes a range of clinical oral mucosal diseases with potentially malignant traits. Dental pulp stem cells (DPSCs) are potential candidates for cell-based therapies targeting various diseases. However, the effect of DPSCs on the progression of oral mucosal precancerous lesions remains unclear. Animal experiments were conducted to assess the effect of human DPSCs (hDPSCs). We measured the proliferation, motility and mitochondrial respiratory function of the human dysplastic oral keratinocyte (DOK) cells cocultured with hDPSCs. Mitochondrial transfer experiments were performed to determine the role mitochondria from hDPSCs in the malignant transformation of DOK cells. hDPSCs injection accelerated carcinogenesis in 4NQO-induced oral epithelial dysplasia in mice. Coculture with hDPSCs increased the proliferation, migration, invasion and mitochondrial respiratory function of DOK cells. Mitochondria from hDPSCs could be transferred to DOK cells, and activated mTOR signaling pathway in DOK cells. Our study demonstrates that hDPSCs activate the mTOR signaling pathway through mitochondrial transfer, promoting the malignant transformation of oral precancerous epithelial lesions.

A novel AI-based score for assessing the prognostic value of intra-epithelial lymphocytes in oral epithelial dysplasia.

Oral epithelial dysplasia (OED) poses a significant clinical challenge due to its potential for malignant transformation and the lack of reliable prognostic markers. Current OED grading systems do not reliably predict transformation and suffer from considerable observer variability. Recent studies have highlighted that peri-epithelial lymphocytes may play an important role in OED malignant transformation, with indication that intra-epithelial lymphocytes (IELs) may also be important. We propose a novel artificial intelligence (AI) based IEL score from Haematoxylin and Eosin (H&E) stained Whole Slide Images (WSIs) of OED tissue slides. We determine the prognostic value of our IEL score on a digital dataset of 219 OED WSIs (acquired using three different scanners), compared to pathologist-led clinical grading. Our IEL scores demonstrated significant prognostic value (C-index = 0.67, p < 0.001) and were shown to improve both the binary/WHO grading systems in multivariate analyses (p < 0.001). Nuclear analyses confirmed the positive association between higher IEL scores, more severe OED and malignant transformation (p < 0.05). This underscores the potential importance of IELs, and by extension our IEL score, as prognostic indicators in OED. Further validation through prospective multi-centric studies is warranted to confirm the clinical utility of IELs.

Oral Leukoplakia: Present Views on Diagnosis, Management, Communication with Patients

Leukoplakia is a mostly white oral mucosal lesion that has a higher chance of developing into cancer.The review's three main goals are to: (1) shed light on the challenges associated with making an accurate diagnosis; (2) assess the most recent findings regarding (bio) markers that may be useful in predicting the likelihood of a malignant transformation; and (3) assess the most recent findings regarding the best course of treatment for patients with oral leukoplakia. Current Research Results The current state of research on oral leukoplakia is very limited, primarily due to the inadequate definition. There are currently no novel (bio)markers that can accurately forecast the onset of malignant transformation. Treatments, both surgical and nonsurgical, have not yet been shown to be successful in stopping such metamorphosis. Synopsis Randomized controlled research on the many elements of oral leukoplakia can only be carried out if the definition's flaws and the lack of uniform reporting problem have been resolved.

Unique genital microbiota in male lichen sclerosus urethral stricture associated with urine exposure

BackgroundLichen sclerosus (LS) is a chronic inflammatory cicatricial skin disease that can lead to urethral stricture or even malignant transformation and the etiology is still unknown. This study comparatively analyzed the balanopreputial swab and urine microbiota simultaneously between male patients with LS urethral stricture (LSUS) and non-LS urethral stricture (non-LSUS).MethodsWe prospectively included 31 male patients with LSUS and 30 with non-LSUS in this case–control study. Midstream urine samples and balanopreputial swabs were collected from each patient for the 16S V3-V4 hypervariable region sequencing. Operational taxonomic units were defined using a > 97% sequence similarity threshold. We compared the differences in alpha diversity, beta diversity, and microbial structure between the two groups.ResultsWhether in swab or urine samples, there was no significant difference in alpha diversity between the two groups. Swab samples showed a significant difference in beta diversity (p = 0.001). For all individuals, composition analyses showed that the most abundant phyla were Actinobacteria, Firmicutes, Proteobacteria, and Bacteroidetes in both samples. Additionally, the microbial communities of swab samples were significantly more similar to the communities of urine samples in the LSUS group (p = 0.047).ConclusionsMicrobiota showed significant variation between LSUS and non-LSUS groups, suggesting that microecological imbalance may be closely related to the occurrence of LS. Urinary irritation may be related to the unique microbiota on the genital skin of patients with LSUS.

Exploring thenew Kyoto guidelines for managing pancreatic cysts: an overview and comparison with previous guidelines.

The rising use of diagnostic imaging has led to an increase in the incidental detection of pancreatic cysts, with reported incidences of 1.2-2.6% on Computed Tomography and 2.4-49.1% on Magnetic Resonance Imaging. While many of these cysts are asymptomatic and benign, the enhanced imaging techniques have also revealed malignant and premalignant lesions. Mucinous neoplasms, including intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms, are particularly concerning due to their potential for malignant transformation. Recent studies highlight significant variations in dysplasia across IPMN types, with main duct IPMNs showing a higher likelihood of high-grade dysplasia or invasive carcinoma compared to branch duct IPMNs. Management and follow-up of these lesions remain controversial due to inconsistent guidelines. This article reviews and compares six major guidelines: the 2015 American Gastroenterological Association guidelines, the 2017 International Association of Pancreatology (IAP/Fukuoka) guidelines, the 2017 American College of Radiology guidelines, the 2018 American College of Gastroenterology guidelines, the 2018 European Study Group guidelines, and the newly released, 2024 Kyoto guidelines. We summarize key differences in risk factors, surveillance protocols, and surgical referral criteria, with a focus on the updated 2024 Kyoto guidelines and the implications of recent research advancements.

Evaluation of sonoelastography in differential diagnostics of endometrial hyperplastic processes

The article presents a description of complex ultrasound diagnostics of endometrial pathology using qualitative and quantitative echography. The parameters of changes in subendometrial and intraendometrial hemodynamics were identified and the average values of rigidity were calculated endometrium in benign and malignant endometrial pathology. The obtained results indicate the high efficiency of the method of qualitative and quantitative assessment of endometrial rigidity in identifying the characteristic features of malignant transformation, which plays an important role in clarifying diagnostics and choosing treatment tactics.

An oncoprotein CREPT functions as a co-factor in MYC-driven transformation and tumor growth

Understanding the mechanisms behind MYC-driven oncogenic transformation could pave the way for identifying novel drug targets. This study explored the role of CREPT in MYC-induced malignancy by generating MYC-transformed mouse embryonic fibroblasts (MEFs) with conditional CREPT deletion. Our results demonstrated that the loss of CREPT significantly impaired MYC-induced colony formation and cell proliferation, indicating that CREPT is essential for the malignant transformation of MEFs. Reintroducing CREPT in CREPT-deficient cells restored malignant properties. Furthermore, CREPT overexpression alone enhanced colony formation upon MYC induction but was insufficient to induce transformation without MYC, suggesting a cooperative interaction between CREPT and MYC in malignant transformation. CREPT deletion resulted in delayed cell cycle progression during the G2/M and S phases. CREPT enhanced the expression of MYC target genes by directly interacting with MYC through the CID domain of CREPT and the PEST domain of MYC. Arginine 34 of CREPT was identified as a critical residue for the interaction with MYC, and its mutation lost the ability of CREPT to promote MYC-driven colony formation and tumor growth in colorectal cancer models. Additionally, CREPT facilitated the recruitment of RNA Polymerase II (RNAPII) to MYC-binding promoters, promoting transcriptional initiation of MYC-targeted genes. Our study also revealed a strong correlation between CREPT and MYC expression in various human cancers, particularly in colorectal cancer, where their interaction appears to play a significant role in tumorigenesis. These findings suggest that the CREPT-MYC interaction is crucial for the progression of MYC-driven cancers and presents a potential target for therapeutic intervention.

Clinical and morphological features of corneal lymphoma in 26 horses (27 eyes).

Little information describing the biologic behaviour and therapies for corneal lymphoma exist. To characterise histologically confirmed equine corneal lymphoma considering breed, age or sex predisposition, histologic and immunologic features, therapies and outcomes. Retrospective case series. A multicentre retrospective medical record review was used to identify horses that presented with corneal disease confirmed morphologically as corneal lymphoma from 2012 to 2022. Mean age at diagnosis was 10.5 years. Males represented 18/26 cases. Warmblood (14) and Thoroughbred (6) breeds were most commonly represented. 25/26 had unilateral ocular involvement. No cases had evidence of multicentric lymphoma. Most eyes (77.7%) had a history of suspected immune-mediated keratitis (IMMK) or eosinophilic keratitis. Morphological diagnosis confirming lymphoma was available for all cases. B-cell lymphoma was diagnosed in 19/24 eyes for which immunohistochemistry was performed, with intermediate to large B-cell lymphoma being most common. Fifteen of 27 eyes received at least one form of adjunctive therapy following keratectomy. Four eyes, which did not receive adjunctive therapy following keratectomy, experienced recurrence. No horses treated with adjunctive therapy following keratectomy experienced recurrence. Malignant transformation of IMMK to lymphoma was morphologically documented in one eye and suspected in three others based on recurrence of clinical signs. All globes were retained and visualised at the last follow-up. Incomplete medical records, owner subjectivity concerning onset of disease and cases being lost to follow-up. Malignant transformation of IMMK to corneal lymphoma likely occurs in horses. Lymphoma should be a differential for nonulcerative keratitis in horses. Keratectomy and histopathology may be considered in progressive or refractory cases of IMMK to rule out neoplastic disease. Recurrence of corneal lymphoma is unlikely following excision and adjunctive therapy. Cases with large corneal surface area or deep stromal involvement may have a likelihood for recurrence.

Update on cancer screening in children with syndromes of bone lesions, hereditary leiomyoma and renal cell carcinoma syndrome, and other rare syndromes.

The management of children with syndromes associated with an increased risk of benign and malignant neoplasms is a complex challenge for healthcare professionals. The 2023 AACR Childhood Cancer Predisposition Workshop provided updated consensus guidelines on cancer surveillance in these syndromes, aiming to improve early detection, intervention, and reduce morbidity associated with such neoplasms. In this paper, we review several of the rare conditions discussed in this workshop. Ollier disease and Maffucci syndrome are enchondromatoses (disorders featuring benign bone lesions) with up to 50% risk of malignancy, including chondrosarcoma. These patients require surveillance with baseline whole-body MRI and routine monitoring of potential malignant transformation of bony lesions. Hereditary Multiple Osteochondromas carry a lower risk of chondrosarcoma (<6%) but still require lifelong surveillance and baseline imaging. Related syndromes of benign bone lesions are also described. Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC), associated with fumarate hydratase pathogenic variants, is discussed in detail. Surveillance for RCC in pediatric age is recommended, as well as prompt intervention when a lesion is detected. Schinzel-Giedion Syndrome and Rubinstein-Taybi Syndrome are described for their associated malignancies and other complications, as well as expert consensus on the need for childhood cancer surveillance. Clinical recommendations, including imaging modalities and frequency of screenings, were proposed and are tailored to each syndrome's age-specific tumor risk profile. In all syndromes, patients and their families should be educated about the potential malignancy risk and advised to seek medical care for rapid growth of a mass, persistent pain, or other unexplained symptoms.

Flip-flop phenomenon on dual SSTR PET and amino acid PET in a case of recurrent meningioma with malignant transformation.

Flip-flop phenomenon on dual SSTR PET and amino acid PET in a case of recurrent meningioma with malignant transformation.

Successful Treatment of Abdominal Wall Advanced Endometriosis-Associated Clear Cell Carcinoma with AKT Pathway Inhibitor: Case Report

The emergence of endometriosis-associated clear cell carcinoma (CCC) within the abdominal wall is a notably rare phenomenon. This condition predominantly impacts females who have previously undergone surgical interventions, including hysterectomy or caesarean section (C-section), with the malignant transformation of endometriosis within the post-surgical abdominal scar posited as a likely mechanism. Herein, we delineate a distinctive case of endometriosis-associated CCC emanating from the abdominal wall. The therapeutic approach for the patient encompassed surgical resection, complemented by a regimen of adjuvant chemotherapy, radiotherapy, immunotherapy, and targeted therapy. Despite these measures, the patient experienced disease progression, manifested by bilateral inguinal lymph node involvement and metastasis to the left femoral bone. Advanced molecular diagnostics, specifically next-generation sequencing (NGS) of the resected specimen, identified a targetable PIK3CA E726K mutation. Subsequent treatment with alpelisib and everolimus was initiated, culminating in a sustained complete response.

Antinuclear Positivity and Malignant Transformation Potential of Oral Potentially Malignant Disorder.

This multicenter cohort study aimed to investigate the impact of antinuclear antibody (ANA) positivity on the malignant transformation potential of oral potentially malignant disorders (OPMDs) using the Observational Health Sciences and Informatics network tools for the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). Retrospective cohort data from five medical centers were analyzed. Cox regression and 1:4 propensity score matching followed by aggregated meta-analysis were used to evaluate association between ANA positivity and the risk of oral squamous cell carcinoma (OSCC). The index date was defined as the first day of diagnosis of OPMD. The target and comparator cohorts comprised patients who tested positive and negative for ANA within 180 days before or after the index date, respectively. Among 27,984 OPMD patients, 1302 patients (4.65%) confirmed malignant transformation. Among these, 3035 patients had ANA laboratory data. After 1:4 PS matching, 523 and 1598 patients with positive and negative for ANA were analyzed. Meta-analysis of the hazard ratios demonstrated that ANA positivity significantly increased the risk of malignant transformation compared to ANA negativity. ANA positivity is a significant prognostic marker for predicting malignant transformation in patients with OPMD.