OncoTargets and therapy最新文献

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide and the third most frequently diagnosed malignancy. Circulating microRNAs, particularly miRNA-92a, have gained prominence as non-invasive biomarkers due to their stability in biological fluids and disease-specific expression patterns.

Objective: This study evaluates the diagnostic performance of circulating miRNA-92a for non-invasive colorectal cancer detection, both as an individual biomarker and in combination with other circulating miRNAs, including markers that are either members of the miRNA-92a family or unrelated miRNA candidates.

Methods: This review was registered in PROSPERO (CRD420251070402). A systematic search of PubMed, ScienceDirect, and Google Scholar was conducted for articles published up to May 2025 in accordance with PRISMA guidelines. Eligible articles evaluated circulating miRNA92a for CRC diagnosis, used appropriate reference standards, and reported extractable sensitivity and specificity data. A bivariate random-effects model in STATA/BE v18.0 was used to generate pooled estimates of sensitivity, specificity, PLR, NLR, logDOR, and AUC. Study quality was assessed using QUADAS-2, and publication bias was examined with Deeks' funnel plot asymmetry test.

Results: Twenty-two studies from sixteen articles, involving 1918 CRC patients and 1446 healthy controls, were included. Circulating miRNA-92a and miRNA-92a-related circulating panels demonstrated pooled sensitivity and specificity of 86% and 91%. Overall diagnostic performance was high, with an AUC of 0.87. The logDOR was 3.71, with a pooled PLR of 18.54 and an NLR of 0.38. Subgroup analyses showed comparable accuracy between singlemarker and panel-based assays, and serum samples yielded more consistent results. QUADAS-2 indicated acceptable methodological quality, and no significant publication bias was detected (p = 0.06).

Conclusion: Circulating miRNA-92a demonstrates superior diagnostic performance and considerable potential as a non-invasive biomarker for early CRC detection. Further large-scale prospective studies are required to standardize testing protocols and confirm their clinical applicability.

[This corrects the article DOI: 10.2147/OTT.S208024.].

Liver cancer is one of the common malignant tumors worldwide and ranks among the top in cancer mortality statistics. In recent years, metformin, as a first-line drug with significant efficacy and low cost, has been widely used in clinical practice for the treatment of diabetes. Now, due to its potential inhibitory effect on cancer cells, it has received extensive attention. In view of this, a large number of studies have focused on the mechanisms by which metformin affects Liver carcinoma, with the AMPK pathway being particularly favored. This is because the AMPK pathway plays a significant role in autophagy, cell cycle arrest, inhibition of tumor angiogenesis, and suppression of epithelial-mesenchymal transition. To this end, we reviewed relevant research literature and systematically explored the mechanism of metformin's treatment of liver cancer through the AMPK pathway and its potential clinical applications. These studies provide an important basis for understanding the potential role of metformin in the treatment of liver cancer and provide important reference for future research on its new mechanisms and its clinical application.

Osteosarcoma (OS) is a highly malignant bone tumor primarily affecting children and adolescents. Clinical treatment has consistently encountered challenges, including chemotherapy resistance, high recurrence rates, and metastasis. Research has demonstrated that epigenetic regulation, particularly DNA methylation, can stably modify the DNA sequence without altering it, playing a key role in the development and progression of OS. Compared with normal tissue, OS exhibits distinctive alterations in DNA methylation, characterized by genome-wide hypomethylation and hypermethylation of specific gene promoter regions. This "dual pattern" not only promotes tumor proliferation, invasion, and metastasis but also maintains cancer stem cell characteristics and modulates the tumor immune microenvironment (TIME). Molecular classification based on DNA methylation profiles offers a new tool for the diagnosis and prognosis of OS. Drugs targeting DNA methylation, such as decitabine, have shown promising results for reversing gene silencing and suppressing tumor progression. This article systematically reviews the core mechanisms by which DNA methylation contributes to OS development, progression, and metastasis, and examines its potential for clinical translation.

[This retracts the article DOI: 10.2147/OTT.S117933.].

[This retracts the article DOI: 10.2147/OTT.S269168.].

Background: The RecQ DNA helicase family member WRN is an important protein for maintaining genome stability. The concept of attention as a synthetic lethal target for MSI-H tumors has garnered significant attention in recent years. However, the role of WRN in cancer development, diagnosis, and prognosis has not yet been systematically evaluated at the pan-cancer level.

Methods: On the basis of multiple public cancer databases, we employed bioinformatics techniques to systematically assess WRN expression, variation, and interaction pathways across various cancers, along with the impact of WRN expression on immune profiling, drug sensitivity, and treatment, as a diagnostic tool. Additionally, we used three cancer cell lines to evaluate the suppressor function of WRN inactivation.

Results: WRN is highly expressed in rapidly proliferating tissues and is dysregulated in a cancer-specific manner, particularly in tumors with hereditary DNA repair deficiencies and myeloid malignancies. WRN expression and variants are correlated with prognosis and immune activation potential in cancers. In digestive cancer and endometrial cancer with a high proportion of MSI-H tumors, WRN is positively associated with MSI/TMB signatures. Pharmacogenomic analyses revealed significant correlations between WRN expression levels and sensitivity to the DNA synthesis inhibitors PI3K, ALK, and IFG1R and other target agents and immunomodulators. In vitro validation using WRN inhibitors demonstrated potent suppression of malignant phenotypes (proliferation, clonogenicity, migration, invasion) in colorectal, endometrial, and ovarian cancer models.

Conclusion: Our study suggests that WRN plays a role in cancer diagnosis and therapy, especially in cancers characterized by replicative stress or defective DNA damage repair, and that WRN can serve as a potential target for cancer immunotherapy or targeted therapies and as a prognostic marker for certain tumors.

Prostate cancer (PCa) is a common urogenital malignancy in elderly males. The typical clinical presentation of advanced PCa includes symptoms of the lower urinary tract. The most common sites of metastasis are the bone and regional lymph nodes. However, PCa with cervical lymphadenopathy as the initial symptom is extremely rare, and one of its variants, foamy gland adenocarcinoma, is even rarer. We present a case of a patient with foamy gland adenocarcinoma of the prostate having enlarged lymph nodes in the neck as the initial symptom. An 81-year-old male was admitted to the hospital with a chief complaint of an enlarged left cervical lymph node without any urological history. Cervical ultrasound showed multiple lymphadenopathies in the left supraclavicular region. The patient underwent a lymph node biopsy, and the pathology results revealed metastatic foamy gland adenocarcinoma of the prostate. Distant lymph node metastasis in PCa is a rare form of metastasis. The initial presentation and tests led to the diagnosis of foamy gland adenocarcinoma of the prostate with cervical lymph node metastasis. Following the diagnosis, the patient received conservative management with androgen deprivation therapy (bicalutamide and goserelin) and zoledronic acid. Unfortunately, he passed away 9 months later due to a COVID-19 infection. We present this rare variant of PCa metastasis to attract the attention of clinicians and pathologists.

Here, we report a case of a male patient who was initially diagnosed with stage IV driver gene-negative lung adenocarcinoma and received immune checkpoint inhibitors plus chemotherapy as first-line therapy. The patient progressed to meningeal metastasis and harbored an EGFR exon20 p.A763V mutation. A double dose of Osimertinib was recommended and the patient achieved a PFS of 10 months. This report offers evidence that Osimertinib may serve as a treatment option for patients with EGFR exon20 p.A763V mutation. In addition, dynamic spatiotemporal heterogeneity of lung cancer cells should be considered when treating patients with EGFR-positive NSCLC.