Colorectal cancer (CRC) ranks as the third most common cancer globally, with significant postoperative recurrence and metastasis rates. The heterogeneity of CRC presents challenges in the selection of adjuvant chemotherapy regimens, highlighting the need for personalized treatment strategies. The development of in vitro models for drug sensitivity testing, including a novel patient-derived tumor-like cell cluster (PTC) model, offers a potential solution for predicting drug efficacy and guiding treatment.

Lung cancer is preceded by premalignant lesions, and what factors drive this transformation and the potential regulatory mode in the context of tumor initiation remain to be elucidated. In the course of precancerous lesions in mice, we found a phasic shift in metabolic patterns. Macrophages are a heterogeneous cell population with high plasticity in the tumor microenvironment. Single-cell interaction and metabolic analyses highlighted a cellular state, S100a4+ alveolar macrophages, which exhibited distinct fatty acid metabolic activity, such as palmitic acid metabolism, at the atypical adenomatous hyperplasia stage, accompanied by an angiogenic-promoting function in a pre-neoplastic setting of mice. These findings were reproducible in human single-cell transcriptomes and had been confirmed by histopathological staining and in vitro cell coculture assays. Taken together, the results from this study demonstrated that the S100a4+ alveolar macrophage subset contributes to tumorigenesis by altering its metabolic state, suggesting that metabolic interventions targeting this cell state in the early stage of disease may delay neoplastic transformation of the lung epithelium.

Background: Vessels encapsulating tumor clusters (VETC) and circulating tumor cells (CTCs) are recognized as emerging potential biomarkers in hepatocellular carcinoma (HCC), yet the underlying connection between them is not fully elucidated. This study aims to investigate the association between VETC and CTCs and evaluate their potential clinical utility. Methods: This retrospective cohort study (NCT05297955) included 165 HCC patients who underwent curative hepatic resection. VETC was identified via CD34 immunohistochemical staining, and preoperative CTC levels were measured using the CellSearch platform. Propensity score matching (PSM) adjusted for confounders, and LASSO-Cox regression was used to develop a prognostic model. Results: VETC-positive tumors were significantly associated with increased disease progression and shorter overall survival (OS) and disease-free survival (DFS). Elevated preoperative CTC counts showed a robust correlation with the VETC phenotype. The co-occurrence of VETC and CTCs emerged as a powerful prognostic indicator for both OS and DFS. A novel DFS prediction model, Vrisk, incorporating VETC, CTC, and four additional factors, demonstrated superior predictive performance compared to conventional staging systems. Conclusions: The study establishes a strong association between VETC, elevated CTC levels, and poorer prognosis in HCC, providing critical insights into their functional roles and potential as biomarkers for clinical applications.

Neoadjuvant chemotherapy (NACT) is the standard treatment for patients with locally advanced breast cancer. In recent years, it has also been used for early-stage triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2-positive (HER2+) breast cancers.

Patients who receive long-term anti-hepatitis B virus (HBV) treatment with nucleos(t)ide analogues (NAs) are still at risk for primary hepatocellular carcinoma (HCC). Aim The purpose of this study was to compare clinical features of HBV-related HCC in NA-treated vs. untreated patients. The records of patients who were diagnosed with HCC for the first time at the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between January 1, 2019 and September 31, 2024 were retrospectively reviewed. Patients with chronic HBV (CHB)-related HCC were grouped into the NA-treated group and untreated group. A total of 562 patients with CHB-related HCC were identified and divided into the NA treatment group (n = 146) and the untreated group (n = 416). Patient age was similar between the groups (50.9 ± 10.1 vs. 52.5 ± 12.1 years, p > 0.05). HBV DNA level, alanine aminotransferase (ALT) level and gamma glutamyl transpeptidase (GGT) level were significantly lower in the NA group (all, p < 0.001). Alpha fetoprotein (AFP) level was significantly higher in the untreated group (p < 0.05). However, the HBeAg positive rate was significantly greater in the NA group (27.4% vs. 17.5%, p < 0.05), and79.5% (116/146) of HCCs occurred in the first 5 years of NA treatment. Blood biochemical indexes and AFP values of patients who develop CHB-related HCC after NA treatment are usually normal. However, the high HBeAg seropositive rate in patients treated with NAs requires attention.

Rapid progression in late-stage is a characteristic of pancreatic cancer (PC), leading to mortality. The critical role of lncRNA A2M-AS1 (long non-coding RNA alpha-2-macroglobulin antisense RNA 1) is involved in cancer progression, but the upstream regulator of A2M-AS1 in the PC progression phenotype remains elusive.

Our understanding of prognostic and predictive factors in the context of nivolumab combined with chemotherapy remains limited. In our multicenter study conducted across 16 centers, data from 153 patients with metastatic gastric adenocarcinoma and a PD-L1 CPS score ≥ 5, who received nivolumab in combination with chemotherapy as first-line treatment, were retrospectively analyzed for the period between 2021 and 2024. The study aimed to investigate the prognostic and predictive significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), Systemic Immune-Inflammation Index (SII), as well as various clinical parameters. The estimated median progression-free survival (PFS) was 11.06 months while the estimated median overall survival (OS) was 16.03 months. Patients who were initially diagnosed with metastatic disease had a significantly worse prognosis, as was those with lung metastases. Lower NLR, PLR, and SII values were associated with longer PFS and OS in the univariate analysis; however, their statistical significance was not mantained in the multivariate analysis. SII and PD-L1 CPS score were determined as independent predictive factors for nivolumab plus chemotherapy treatment response. Our study is the only one to date that sheds light on prognostic and predictive factors in patients with metastatic gastric or GEJ adenocarcinoma and a PD-L1 CPS score ≥ 5, who received nivolumab in combination with chemotherapy.

Neurofibromatosis type 1 (NF1) is a rare genetic disorder with highly variable phenotypes, ranging from psychosocial challenges and congenital malformations to benign tumors and even aggressive cancers. We hypothesize that this variability stems from additional rare variants in other genes, in addition to NF1 variants. The analysis of 32 NF1 patients revealed that those with solid cancers carried a higher average of cancer driver variants especially in DNA repair genes compared to those without (p < 0.05). An extended validation study using 217 NF1 carriers (71 cancer and 146 controls) from UK biobank confirmed significant enrichment of pathogenic (P), likely pathogenic (LP) and uncertain significant (VUS) variants in DNA repair genes, in NF1 patients with tumors (FDR ≤ 0.05). Furthermore, P/LP variants in other genes are shown in those patients with NF1 ancillary traits such as cognitive impairments, macrocephaly, and connective defects. This study provides novel evidence suggesting that additional genetic variants in other genes may contribute to the phenotypic variability observed in NF1, indicating that rare secondary mutational events could influence specific manifestations, adding complexity to its variable expressivity.

Transcription factors (TFs) are pivotal in tumor initiation and progression, regulating downstream gene expression and modulating cellular processes. In this study, we conducted a comprehensive analysis of TF gene sets to define the molecular subtypes of gliomas. Using nonnegative matrix factorization (NMF), we identified two distinct glioma subtypes characterized by significant differences in survival outcomes and clinical features. Additionally, we identified TF gene sets with differential expression across gliomas of various World Health Organization (WHO) states, followed by protein‒protein interaction (PPI) network analysis. By applying 101 machine learning models, five key genes (EZH2, TWIST1, EGR1, FOSL2, and TCF3) involved in glioma were identified. Among these genes, TCF3 has emerged as a potential key prognostic marker because of its distinct expression patterns and functional relevance. By performing multi-omics and multi-dataset analyses, we explored the aberrant expression of TCF3 across multiple cancers, with robust validation at both the cellular and tissue levels. Furthermore, our analysis revealed a strong association between TCF3 mutation and glioma prognosis, underscoring its potential as a therapeutic target. In summary, this study not only introduces a novel method for the molecular subtyping of glioma but also highlights TCF3 as a promising target for precision medicine. Our findings provide crucial insights into the molecular mechanisms of glioma and offer a foundation for the development of novel therapeutic strategies.

Lung cancer is the most common malignant tumour and the leading cause of cancer-related death. circular RNAs (circRNAs) have important biological functions and are closely related to tumour development. The 5-methylcytosine (m5C) modification can regulate the molecular fate of RNA molecules and thus influence disease development.

Metabolic reprogramming is a hallmark of cancer, with acute myeloid leukemia (AML) being no exception. Mitochondrial function, particularly its role in protecting tumor cells against chemotherapy, is of significant interest in AML chemoresistance. In this study, we identified mitochondrial DNA content (mtDNAc), measured by quantitative PCR, as a simple and precise marker to stratify the metabolic states of AML patients. We show that patients with high mtDNAc are associated with increased mitochondrial metabolism and a higher dependency on oxidative phosphorylation (OXPHOS), often correlating with chemoresistance. Clinically, patients receiving cytarabine and an anthracycline-based regimen (7 + 3 regimen) experienced inferior relapse-free survival and a higher overall rate of leukemia recurrence. Ex vivo experiments using primary AML samples confirmed cytarabine resistance in high mtDNAc patients, which could be overcome by inhibiting mitochondrial complex I. The FDA-approved drug metformin, which targets mitochondrial metabolism, significantly enhanced apoptosis in response to chemotherapy or targeted agents, such as venetoclax, in AML models. However, metformin-treated cells adapted by increasing glycolysis and NAD+ production, a resistance mechanism that could be bypassed by targeting the nicotinamide phosphoribosyltransferase (NAMPT) enzyme. In summary, we demonstrated that mtDNAc is an effective tool for assessing the metabolic state of AML cells. This method can be easily implemented in clinical practice to identify chemoresistant patients and guide personalized treatment strategies, including novel combination therapies for those with a high reliance on mitochondrial metabolism.

Nucleoli are large nuclear sub-compartments where vital processes, such as ribosome assembly, take place. Most nucleolar proteins are essential; thus, their abrogation cannot be achieved through conventional approaches. This technical obstacle has limited our understanding of the biological functions of nucleolar proteins in cell homeostasis and cancer pathogenesis.

Ionizing radiation is known to induce brain tumors such as meningiomas and gliomas over a time. Similar tumorogenic effects have been described with chemotherapeutic agents also. However, the literature is sparse regarding this entity. There has been some new understanding derived from the molecular studies regarding the mechanism of such tumorogenesis. To highlight such updates in the current knowledge is the objective. Two patients treated for malignancy in their childhood developed meningiomas in later part of their life. This highlights the possibility of developing meningiomas or other endocrinal tumors following the treatment for malignancy at a younger age. The need for long-term follow-up of these patients is the highlight of the report. Both the meningiomas were successfully removed surgically with favorable clinical outcomes. However, prevalence and risk projection need to be identified to plan the clinical management and long-term follow-up. Though meningiomas are known to be induced by previous radiotherapy, the exact mechanisms are not yet clear. Recent research indicates the genetic abnormalities and molecular abnormalities that can induce or evolve Meningiomas following radiotherapy. These tumors seem to form a distinctly different group molecularly and can be aggressive clinically. Understanding biomolecular pathogenesis is important to manage such patients adequately.

This study aimed to report our experiences with the safety and reliability of frameless stereotactic brain biopsy, including eloquent areas and small-sized lesions.

tRNA-derived small RNAs (tsRNAs), newly developed non-coding RNAs with specialized biological features, are aberrantly expressed in the majority of malignancies. However, whether tsRNAs are involved in metabolic reprogramming of colorectal cancer (CRC) remains to be elucidated.

BCMA-directed CAR-T therapies have shown promising results in multiple myeloma (MM). However, patients continue to relapse. T cell exhaustion with increased TIGIT expression is a resistance mechanism which was confirmed in CAR-T cells from ARI0002h trial, an academic CAR-T developed in our institution. We aimed to analyze the impact of blocking TIGIT on the efficacy of ARI0002h. We used three different strategies to block TIGIT: (1) Addition of an external blocking anti-TIGIT-antibody (Ab), (2) Modify ARI0002h into a 4th generation CAR-T, named ARITIGIT, capable of secreting a soluble TIGIT-blocking scFv and (3) TIGIT knock-out in ARI0002h using CRISPR/Cas9. Each strategy was evaluated in vitro and in vivo. Adding a TIGIT-blocking Ab to ARI0002h improved in vitro cytotoxicity, but failed to enhance mice survival. The new 4th generation CAR-T, ARITIGIT, was also unable to achieve better survival outcomes despite favoring the in vivo model by using a myeloma cell line with high expression of the TIGIT ligand PVR. Interestingly, when mice were challenged with a second infusion of tumor cells, mimicking a relapse model, a trend for improved survival with ARITIGIT was observed (p = 0.11). Finally, TIGIT-knock-out on ARI0002h (KO-ARI0002h) using CRISPR/Cas9 showed similar in vitro activity to ARI0002h. In an in vivo stress model, TIGIT KO-ARI0002h prolonged survival (p = 0.02). However, this improvement was not significant compared to ARI0002h (p = 0.07). This study failed to demonstrate a significant benefit of TIGIT-blockade on ARI0002h cells despite using three different approaches, suggesting that targeting a single immune checkpoint may be insufficient.

Prostate adenocarcinoma (PRAD) is asymptomatic in the early stages and most patients are diagnosed at an advanced stage, which leads to a poor prognosis. Therefore, an effective prognostic marker is required to improve PRAD prognosis.

Colorectal liver metastases (CRLM) are the leading cause of colorectal cancer (CRC)-related mortality. Transfer RNA-derived fragments (tRFs), a novel class of small non-coding RNAs (sncRNA), regulate gene expression, stress response, and immune functions in cancer. While increasingly implicated in CRC progression, their prognostic significance in CRLM remains unknown. This study investigates the abundance and prognostic value of genomic (ge) and mitochondrial (mt) tRFs in CRLM.

Circulating tumor DNA (ctDNA) holds promise for guiding immune checkpoint inhibitor (ICI) therapy and stratifying responders from non-responders. While tumor-informed ctDNA detection approaches are sensitive and mutation-inclusive, they require tumor tissue, which limits applicability in real-world settings. Conversely, tumor-agnostic methods often have limited genomic coverage. In this study, we evaluated a tumor-agnostic, broad-panel ctDNA assay in patients with advanced melanoma treated with ICI.

The role of axillary surgery in ductal carcinoma in situ (DCIS) remains controversial, particularly for cases diagnosed via vacuum-assisted biopsy (VAB), which may reduce "upstage" to invasive disease. This study evaluates the incidence of axillary metastasis and pathologic upstaging in DCIS to identify subgroups where axillary staging can be safely omitted.