Kelch-like ECH-associated protein 1 (KEAP1) regulates the NRF2 signaling pathway and plays a critical role in oxidative stress response and tumor suppression. Promoter hypermethylation of KEAP1 may contribute to carcinogenesis; however, its association with cancer remains unclear.

Exosomal microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for hepatocellular carcinoma (HCC). Nevertheless, the overall diagnostic performance of exosomal miRNAs in HCC was still less reported. Therefore, this meta-analysis aimed to systematically assess the pooled diagnostic efficacy of exosomal miRNAs for HCC.

Post-neoadjuvant circulating tumor DNA (ctDNA) has been investigated as a minimal residual disease (MRD) marker in stage I-III triple-negative breast cancer (TNBC), but landmark timing and assay approaches vary.

Although prognostic stratification has improved with the use of molecular classification in endometrial cancer staging, it is still unclear how this will affect lymph-node metastasis in modern surgical practice. The objective of this meta-analysis was to update and refine pooled estimates of lymph-node metastasis prevalence across the molecular subtypes of endometrial cancer.

Background and objectives Oral squamous cell carcinoma (OSCC) represents the predominant form of oral cancer and remains a major cause of morbidity and mortality worldwide. Beyond traditional risk factors such as tobacco, alcohol, and betel quid consumption, mounting evidence implicates chronic inflammation as a driving force in oral carcinogenesis. This review synthesises current literature exploring how inflammatory mediators contribute to tumour initiation, progression, and clinical outcomes in OSCC. Methods A systematic search of PubMed, Scopus, Web of Science, Embase, and Cochrane Library databases was conducted according to PRISMA 2020 guidelines. Studies from 2020-2025 examining molecular and clinical interactions between inflammation and OSCC were analysed. Extracted data included inflammatory biomarkers, activated signalling pathways, and prognostic or therapeutic implications. The risk of bias was assessed using the Newcastle-Ottawa Scale and Cochrane RoB-2 tool. The review protocol was registered with PROSPERO (CRD420251141942). Results Forty-three eligible studies revealed that inflammatory cytokines such as TNF-α, IL-6, and IL-1β, together with chemokines like CXCL8, trigger oncogenic cascades involving NF-κB and STAT3, leading to enhanced proliferation, angiogenesis, and epithelial-mesenchymal transition. Oxidative DNA damage and immune suppression mediated by M2 macrophages and PD-1/PD-L1 signalling further facilitate tumour aggressiveness. Elevated COX-2, STAT3, and systemic inflammatory ratios were strongly associated with poor prognosis. Interpretation and conclusions Persistent inflammation acts as a critical determinant in OSCC pathogenesis. Integrating inflammation-related biomarkers and anti-inflammatory therapeutic strategies may improve early detection, prognostication, and patient survival outcomes.

Human papillomavirus (HPV)-based cervical screening offers stronger protection against cervical intraepithelial neoplasia (CIN) than screening with cytology. DNA methylation tests have been proposed as an alternative triage test to cytology, although there is currently no consensus on the most accurate gene or gene panels ("markers").

Brain metastases are a major contributor to morbidity and mortality in patients with advanced solid tumors; however, early detection and accurate prognostic assessment remain significant clinical challenges. ctDNA is a minimally invasive biomarker that allows real-time monitoring of tumor behavior and provides information on systemic tumor burden and molecular diversity. This study aimed to systematically evaluate the diagnostic and prognostic value of ctDNA in brain metastases, with particular emphasis on the complementary roles of plasma and CSF ctDNA.

KRAS G12C mutations occur in approximately 3%-4% of metastatic colorectal cancer (mCRC) cases. While the introduction of KRAS G12C inhibitors has transformed the therapeutic landscape for this molecular subset, conflicting evidence exists regarding the independent prognostic impact of this mutation in inhibitor-naïve settings. Small sample sizes and methodological heterogeneity have limited individual studies, precluding definitive conclusions. To address this knowledge gap, we conducted a systematic review and meta-analysis to establish the prognostic significance of KRAS G12C mutations in mCRC.

Sinonasal squamous cell carcinoma (SNSCC) is a rare malignancy with variable outcomes, and the prognostic impact of molecular alterations remains incompletely defined. This meta-analysis aims to clarify the associations of genetic alterations and protein expression with clinical outcomes in SNSCC.

Women with a family history of breast cancer have an elevated risk of developing the disease. In clinical practice, the probability of developing breast cancer over a specified timeframe is frequently estimated using breast cancer risk prediction models. It is currently unclear which of the available models performs best in women with a breast cancer family history.

Postoperative circulating tumor DNA (ctDNA) is an emerging biomarker for molecular residual disease (MRD) detection in early-stage colorectal cancer (CRC). However, its prognostic value in patients with resected metastatic disease has not been comprehensively assessed. This study aimed to evaluate the association between postoperative ctDNA detection and survival outcomes, including after completion of adjuvant chemotherapy (post-ACT), in patients with metastatic CRC (mCRC) treated with curative intent.

The co-occurrence of glioblastoma (GBM) and meningioma in a single patient is an exceptionally rare clinical phenomenon, often associated with prior irradiation or genetic syndromes. This study presents a unique case of concurrent de novo GBM and meningiomatosis and provides a systematic review of the literature to characterize this rare association.

DICER1 is a key RNase III endoribonuclease involved in microRNA biogenesis and is implicated in both constitutional DICER1-related tumor predisposition and sporadic thyroid tumorigenesis. In thyroid pathology, DICER1 alterations have been reported across a broad spectrum of lesions, but their reported frequency and clinicopathologic significance vary substantially across published series. We performed a systematic review of thyroid-focused studies published between 2020 and 2025. Studies were included in the quantitative synthesis only if they provided an interpretable lesion-level numerator and denominator for thyroid lesions harbouring DICER1 alterations. Additional thyroid-focused studies that refined the cytomorphologic, histologic, and lesion-spectrum interpretation of DICER1-associated thyroid disease, but lacked a suitable denominator for prevalence meta-analysis, were retained for qualitative clinicopathologic synthesis. Random-effects meta-analysis of logit-transformed proportions was used for the quantitative component. Seven studies met criteria for quantitative synthesis, comprising 16,831 thyroid lesions, of which 317 were reported as DICER1-altered. Study-level proportions ranged from 1.4% in a large adult consecutive molecular-testing cohort to 22.0% in a pediatric follicular-patterned tumor cohort. The pooled proportion of thyroid lesions harbouring DICER1 alterations was 5.76% (95% CI, 2.49%-12.78%), with substantial heterogeneity (I² = 96.94%). Exploratory stratification showed lower pooled proportions in predominantly adult cohorts and higher pooled proportions in pediatric or young-enriched cohorts. Qualitative synthesis showed that DICER1 alterations occur across a wide thyroid lesion spectrum, including multinodular and follicular nodular disease, follicular adenoma, NIFTP, follicular thyroid carcinoma, follicular-patterned papillary thyroid carcinoma, and rare higher-grade or primitive malignant tumors such as thyroblastoma. Cytologically and histologically, these lesions frequently show follicular-patterned architecture, often with macrofollicular or mixed follicular growth and relatively bland nuclear features.Seven studies met criteria for quantitative synthesis, comprising 16,831 thyroid lesions, of which 317 were reported as DICER1-altered. Study-level proportions ranged from 1.4% in a large adult consecutive molecular-testing cohort to 22.0% in a pediatric follicular-patterned tumor cohort. The pooled proportion of thyroid lesions harbouring DICER1 alterations was 5.76% (95% CI, 2.49%-12.78%), with substantial heterogeneity (I² = 96.94%). Exploratory stratification showed lower pooled proportions in predominantly adult cohorts and higher pooled proportions in pediatric or young-enriched cohorts. Qualitative synthesis showed that DICER1 alterations occur across a wide thyroid lesion spectrum, including multinodular and follicular nodular disease, follicular adenoma, NIFTP, follicular thyroid carcinoma, follicular-patterned papillary thyroid carcinoma, and rare higher-grade or primitive malignant tumors such as thyroblastoma. Cytologically and histologically, these lesions frequently show follicular-patterned architecture, often with macrofollicular or mixed follicular growth and relatively bland nuclear features. DICER1 alterations are uncommon in large unselected adult thyroid cohorts but enriched in pediatric, young-adult, and follicular-patterned settings. They should not be interpreted as isolated lesion-specific markers. Rather, their diagnostic significance lies in the integration of molecular findings with lesion type, cytomorphology, histology, patient age, and clinical context, including the selective recognition of cases in which constitutional DICER1-related tumor predisposition should be considered.

This systematic review aimed to synthesize and critically appraise molecular differences between oral squamous cell carcinoma arising in the background of oral submucous fibrosis (OSCC-OSMF) and OSCC without OSMF (OSCC-non-OSMF) across genomic, transcriptomic, proteomic, and immunohistochemical domains.

Two new tests, a cell-free DNA (cfDNA) blood-based test (BBT) and multitarget stool RNA (mt-sRNA) test with in-laboratory fecal immunochemical testing, were recently approved by the US Food and Drug Administration, and a second BBT is under review. These tests have the potential to overcome barriers to screening. This review evaluates the current evidence to better understand their utility for routine screening. The authors searched PubMed, other databases, and gray literature sources through March 30, 2026. Included studies examined the diagnostic accuracy, harms, and the adherence to cfDNA and mt-sRNA screening tests for colorectal cancer (CRC). One investigator abstracted data, and a second confirmed. Two investigators independently assessed the risk of bias and strength of evidence. Discords were resolved through consensus. From 262 titles, 12 studies (17 publications) were included. Three studies provide moderate strength evidence to support the performance characteristics of cfDNA, and one provides low strength evidence for mt-sRNA. For cfDNA, adjusted CRC and advanced precancerous lesions sensitivities ranged from 80.8% to 81.1% and from 12.9% to 13.7%, respectively, and advanced colorectal neoplasia specificity ranged from 89.5% to 90.4%. For mt-sRNA, CRC sensitivities were 93% and 48%, and observed specificity was 90%. No studies reported serious harms, and the evidence comparing adherence was insufficient. We found that cfDNA screening tests for CRC are similar, and although mt-sRNA estimates fall below those demonstrated by mt-sDNA, its in-laboratory fecal immunochemical testing, has the potential to increase adherence. Future research examining adherence is needed, as are data from which to examine their impact on underrepresented populations.

Phyllodes tumours (PTs) of the breast are rare fibroepithelial neoplasms with potentially aggressive behaviour, characterised by rapid growth, a significant risk of local recurrence, and occasional metastatic spread. Optimal management remains controversial, particularly regarding surgical margins, adjuvant radiotherapy, and the relevance of molecular markers in predicting tumour behaviour. A PRISMA 2020-guided qualitative systematic review was conducted of studies published between January 2000 and December 2024 in PubMed/MEDLINE, Scopus, and Web of Science. Eligible studies included malignant PTs of the breast and addressed at least one of the following domains: molecular pathology, surgical margins and local recurrence, adjuvant radiotherapy, or predictors of recurrence and metastasis. A clinical case of malignant PT treated at our institution is presented as an illustrative study. Thirty-four studies met the inclusion criteria. Evidence suggests that margin status, stromal proliferative activity, and selected molecular markers influence recurrence risk. Several retrospective studies suggest that adjuvant radiotherapy may improve local control in selected high-risk malignant PTs, although the evidence remains heterogeneous, retrospective, and potentially affected by treatment-selection bias, and no consistent survival benefit has been demonstrated. Molecular alterations, including MED12 mutations, TERT promoter mutations, TP53 alterations, and increased Ki-67 expression, have been associated with tumour progression and aggressive behaviour. A 44-year-old woman presented with a 2.4 cm left breast mass on radiological examination. Lumpectomy revealed a malignant PT with stromal hypercellularity, nuclear atypia, and a mitotic index of 20/10 HPF with close margins. Immunohistochemistry showed positivity for CD99, Bcl-2, and CD34 with a Ki-67 proliferation index of 20%. The patient underwent wide local re-excision followed by adjuvant radiotherapy (60 Gy), and at 24-month follow-up, the patient remained disease-free. Evidence synthesis highlights the importance of complete surgical excision, multidisciplinary management, and consideration of adjuvant radiotherapy in selected malignant PTs. Emerging molecular profiling may contribute to improved biological understanding and future risk stratification of malignant PTs, although its routine clinical utility remains to be validated in prospective studies.

Accurate, non-invasive detection of urothelial carcinoma (UC) remains an unmet clinical need. Urinary tumor DNA (utDNA) assays have recently emerged as promising tools, but their comparative diagnostic performance across assay types remains uncertain. We conducted a systematic review and network meta-analysis in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 statement. PubMed, Cochrane Library, Web of Science, Google Scholar, and Clinical Trials.gov were searched through January 2025. We included studies evaluating the diagnostic accuracy of utDNA for UC detection and surveillance. Data were pooled using a frequentist random-effects model to estimate sensitivity, specificity, diagnostic odds ratios, and area under the curve (AUC). A total of 37 studies comprising 7,388 patients were included. The pooled sensitivity and specificity of utDNA were 79% (95% confidence interval [CI], 73%-84%) and 86% (95% CI, 83%-89%), respectively. utDNA demonstrated over 4-fold higher sensitivity than urine cytology while maintaining comparable specificity. Analysis method significantly affected sensitivity, with next-generation sequencing (NGS)-based methods showing higher sensitivity (0.83) compared with methylation-based methods (0.75; P = 0.01). Urinary tumor DNA testing offers clinically meaningful accuracy and could reduce the need for invasive cystoscopy in UC diagnosis and surveillance. Implementation studies and cost-effectiveness analyses are warranted to support integration into clinical practice. Clinical Trial Registration PROSPERO CRD420251011665.

A systematic review was conducted to evaluate the available evidence regarding the tumorigenic and metastatic roles of serine/arginine protein kinase 2 (SRPK2) across different cancer types. A range of preclinical studies was included, generally addressing four main aspects: cancer-related signalling pathways involving SRPK2; its prognostic associations; its impact on metastatic and/or tumour phenotypes; and the antitumor and/or antimetastatic effects resulting from its inhibition. Here, we summarise and discuss the mechanisms through which SRPK2 exerts its oncogenic functions, as well as the therapeutic potential of targeting this kinase. SRPK2 may promote cancer development through its canonical role in alternative splicing, as well as through its involvement in diverse cellular signalling pathways. Moreover, elevated SRPK2 expression across multiple human malignancies consistently correlates with poor clinical outcomes. Collectively, these findings highlight SRPK2 as a promising therapeutic target and potential tumour biomarker.

Colorectal cancer (CRC) is the third most common cancer globally, with rising cases in Latin America. MSI-H and MMRd play key roles in CRC, but data on their prevalence in Hispanic/Latino populations are limited. This study evaluates these biomarkers in the region.

Histological transformation represents an important mechanism of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant lung cancer; however, its incidence, timing, and post-transformation outcomes remain incompletely characterized.