Lung cancer remains one of the most prevalent and lethal malignancies worldwide, characterized by a poor prognosis and high mortality rates. Although therapeutic strategies targeting oncogenic signaling cascades, such as receptor tyrosine kinases, have shown promising outcomes by regulating cellular functions such as survival and proliferation, their long-term effectiveness is often limited by mechanisms, including tumor resistance, drug toxicity, and adverse events. These challenges underscore the urgent need to identify new molecular targets and develop alternative therapeutic approaches. One promising avenue lies in the exploration of microRNAs (miRs) and their significance in cancer biology. Among them, miR-218 has drawn significant attention for its tumor-suppressive properties. Multiple experimental studies have emphasized the role of miR-218 as a key regulator of cell signaling pathways critical to cancer progression, including proliferation, invasion, metastasis, and apoptosis. Notably, miR-218 has been investigated as both a diagnostic biomarker and a therapeutic target. Importantly, clinical evidence further supports its relevance, showing an inverse correlation between miR-218 expression levels and tumor aggressiveness, reinforcing its translational significance. This review logically consolidates the functional significance, mechanistic insights, and experimental and clinical findings that emphasize the pivotal role of miR-218 in regulating molecular pathways involved in lung cancer growth.
Aim: Medication-related osteonecrosis of the jaw (MRONJ) challenges clinicians with its complex pathology and high risk of complications.
Methods: We searched seven databases - PubMed, Scopus, Web of Science, Cochrane Library, Embase, CINAHL, and Google Scholar - and adapted the search strings for each database to optimize retrieval of relevant studies. We then systematically reviewed the included studies to identify the most effective treatments for promoting MRONJ healing.
Results: A total of 329 records were identified through database searches across seven electronic databases. After removal of 45 duplicates, 284 records were screened. Following title and abstract screening and full-text assessment, 13 studies met the eligibility criteria and were included in the qualitative synthesis. The included studies consisted primarily of randomized controlled trials and retrospective cohort studies investigating surgical, pharmacological, and adjunctive therapeutic strategies for MRONJ management. Risk-of-bias assessment using the RoB 2.0 and ROBINS-I (Risk of Bias in Non-randomised Studies - of Interventions) tools showed that most studies presented low to moderate risk of bias, although some methodological concerns were identified. Surgical interventions were commonly associated with improved clinical healing, while adjunctive therapies such as bone morphogenetic protein-2 and teriparatide showed promising outcomes in selected cases. Follow-up periods ranged from 1 month to 2 years, and outcome measures included clinical, radiological, and histological evaluations.
Conclusion: MRONJ treatment is diverse and multifaceted. Such inferences were made to varying degrees in previous investigations, illustrating the limitations for clinical use, revealing the need for further studies to clarify both the efficacy and optimal use of the interventions in diverse clinical settings.
Background: The FAM (family with sequence similarity) gene family, implicated in various malignancies, remains underexplored in microsatellite-stable (MSS) colorectal cancer (CRC). MSS CRC represents the majority of CRC cases and lacks reliable prognostic biomarkers as well as effective immunotherapeutic strategies.
Methods: Transcriptome profiles and matched clinical data from The Cancer Genome Atlas-COADREAD cohort were used as a training set, while GSE29623 and GSE39582 served as independent validation cohorts. A prognostic signature (FAM gene Family-associated expression scoring (FAMscore)) was constructed based on FAM family genes using Multivariate-Cox regression. Associations between FAMscore, survival outcomes, tumor immune microenvironment features, and predicted drug sensitivity were explored through computational analyses.
Results: The FAMscore stratified MSS CRC patients into high- and low-risk groups with significantly different (P ≤ 0.05) overall survival (OS) in the training cohort and consistent trends in validation datasets. A high FAMscore was associated with an immunosuppressive tumor immune microenvironment, characterized by increased regulatory T cells and M2 macrophages. Exploratory analyses suggested differential predicted sensitivity to selected targeted agents.
Conclusions: FAMscore is associated with prognosis and immune landscape features in MSS CRC. These findings are exploratory and hypothesis-generating, and further experimental and prospective validation is required.
Recent advances in the management of early-stage non-small cell lung cancer (NSCLC), including perioperative immunotherapy and targeted treatments, have significantly improved outcomes. Nevertheless, a considerable proportion of patients relapse after curative-intent surgery, emphasizing the need for biomarkers that can more accurately define recurrence risk and guide individualized treatment. Circulating tumor DNA (ctDNA) has emerged as a promising, non-invasive biomarker for detecting minimal residual disease (MRD), assessing molecular response, and identifying relapse before clinical or radiologic evidence. Across retrospective and prospective studies, ctDNA detection at baseline or after treatment is consistently associated with inferior recurrence-free and overall survival, with postoperative positivity marking patients at the highest risk of relapse, often several months ahead of imaging findings. Evidence from recent pivotal trials further reinforces the prognostic significance of ctDNA dynamics in the perioperative setting. However, translation into clinical practice remains limited. ctDNA detection in early-stage disease is inherently challenging due to its low abundance and technical variability across assays. Moreover, no platform is yet validated or approved for MRD detection in this setting, and the predictive impact of ctDNA-guided treatment adaptation remains to be demonstrated. Ongoing efforts are focused on refining assay sensitivity, standardizing workflows, and conducting prospective interventional trials to establish ctDNA as a clinically actionable biomarker. This review provides an overview of current evidence, emerging technologies, and future directions toward clinical integration of ctDNA in resectable NSCLC.
Aim: To elucidate integrin β5 (ITGB5)-associated transcriptomic alterations in hepatocellular carcinoma cells and identify key coding and non-coding RNA regulators and their associated signaling pathways.
Methods: Whole-transcriptome sequencing was conducted on HepG2 (human hepatocellular carcinoma cell line) cells overexpressing ITGB5. Differential expression analysis was performed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses for messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Candidate transcripts were validated using real-time quantitative polymerase chain reaction (RT-qPCR).
Results: ITGB5 overexpression induced extensive transcriptomic alterations. KEGG enrichment highlighted the phospholipase D, vascular endothelial growth factor (VEGF), and ErbB signaling pathways, with significant involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) cascades. Pathway-level analyses suggested a relative attenuation of PI3K/Akt signaling alongside the preferential engagement of MAPK/ERK-related programs. GO analysis indicated shifts in biological processes, notably the negative regulation of peptidase activity and cell-matrix adhesion. Furthermore, ITGB5 was associated with widespread lncRNA and circRNA regulation; predicted target genes of these non-coding RNAs were enriched in PI3K/Akt signaling, protein processing in the endoplasmic reticulum, and cell cycle regulation. RT-qPCR confirmed the upregulation of key transcripts, including dystroglycan 1 (DAG1; mRNA), small nucleolar RNA host gene 1 (SNHG1; lncRNA), and circFN1 (circRNA), in ITGB5-overexpressing cells.
Conclusion: Our findings identify ITGB5 as a regulatory hub in hepatocellular carcinoma (HCC) associated with coding and non-coding RNA regulatory networks, offering insights into potential therapeutic targets.
Aim: Neoadjuvant immunochemotherapy (nICT) has shown promising efficacy in locally advanced esophageal squamous cell carcinoma (LA-ESCC), but reliable predictors of pathological response and prognosis remain lacking. This study aimed to evaluate the predictive value of hematologic indicators for pathological complete response (pCR) and survival outcomes in LA-ESCC patients treated with nICT.
Methods: A total of 204 LA-ESCC patients who received nICT followed by curative esophagectomy were retrospectively analyzed. Baseline and preoperative hematologic indices were collected to calculate neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, and C-reactive protein-to-albumin ratio (CAR). Logistic regression factors identified associated with pCR, and a nomogram was developed and internally validated. Kaplan-Meier analysis and Cox regression analyses were performed for disease-free survival (DFS) and overall survival (OS).
Results: Among the 204 patients, 59 achieved pCR, with a pCR rate of 28.9%. Multivariate logistic regression identified lower baseline NLR, lower preoperative NLR, lower preoperative CAR, earlier clinical Tumor-Node-Metastasis stage, and better tumor differentiation were independently associated with pCR. The nomogram showed good discrimination with a concordance index (C-index) of 0.816 and a bootstrap-corrected C-index of 0.792. In multivariate Cox analysis, low baseline NLR, female, and pCR were associated with longer DFS, while low baseline NLR and pCR were associated with prolonged OS.
Conclusion: Lower NLR and CAR were associated with improved pathological response and survival outcomes. The nomogram may serve as a convenient adjunctive tool for individualized pCR prediction, but external validation is required.
Tumor metabolic reprogramming serves as a fundamental driver of malignancy, fueling cancer cell growth while reshaping the immune landscape through metabolite accumulation. Ferroptosis, an iron-dependent form of regulated cell death, is intricately linked to these metabolic shifts. In the tumor microenvironment, tumor-associated macrophages (TAMs) are pivotal in modulating immune evasion and therapeutic resistance through diverse and context-dependent functional states. Emerging evidence suggests that metabolic alterations can dictate TAM functional plasticity by intersecting with ferroptosis-related pathways. However, the precisely orchestrated mechanisms within the “tumor metabolism-ferroptosis-TAM” axis remain to be fully integrated. This narrative review critically examines current evidence on tumor metabolic reprogramming and its impact on ferroptosis and TAM functional-state remodeling. We specifically focus on the molecular crosstalk through which metabolic and ferroptosis-associated signals may shape macrophage inflammatory, immunoregulatory, tissue-remodeling, and oxidative-stress-associated programs, and discuss potential combinatorial strategies targeting this regulatory axis.