Colon cancer is a highly aggressive solid tumor. Because most studies have focused on the intrinsic oncogenic pathways of tumors, we focused on the relationship between DNA methylation genes in the tumor immune microenvironment and colon cancer prognosis. We download RNA-seq data from the TCGA dataset. DNA methylation genes were scored using the GSVA method, and this score was subjected to GSEA, GO and KEGG enrichment analysis. Then, in vitro experiments examined the effect of silencing LARS2 on the proliferation and apoptosis of HCT116 cells. We obtained 2635 genes, 144 were obtained after single factor screening, and 8 genes were obtained through random forest dimensionality reduction. They are LARS2, TEX2, BRIP1, QSOX2, HOOK1, COX19, NEK4 and STXBP4. Survival analysis indicated that patients with high Riskscore had poor prognosis. There were significant differences in the expression of DNA methylation genes between the two groups with high and low Riskscore. The immune checkpoints of different Riskscore groups include Antigen present, Ligand, Receptor, Co-inhibitor, Co-stimulator, Other, and Cell adhesion. There were significant differences in the expression of genes and DNA integrity checkpoint, histone deacetylation, mitotic DNA damage checkpoint, TGF-beta signaling pathway, Platinum drug resistance and Protein processing in endoplasmic reticlum pathway at the level of Antigen present. Silencing of LARS2 decreased the proliferative capacity and increased the apoptosis rate of HCT116. Our findings suggest that LARS2 methylation could affects colon cancer development.

Tumorigenesis is a microevolutionary process in which heterogeneous tumor cells adapt within a complex microenvironment. Current tumor omics analyses often focus exclusively on tumor samples, overlooking the valuable insights that normal tissues can provide. To address this gap, we introduce VaDTN (Variational Autoencoder-Derived Tumor-to-Normal), a pan-cancer framework that integrates transcriptomic data from both tumor and normal samples into a unified latent space. By measuring each tumor's "distance" from a normal reference within this latent space, VaDTN reveals subtle molecular shifts linked to tumor evolution and heterogeneity. We applied VaDTN to six representative cancers (SKCM, BRCA, LIHC, LUSC, STAD, and PAAD), identifying distinct subtypes characterized by unique transcriptional profiles. Notably, four cancer types (SKCM, BRCA, LIHC, and STAD) displayed significant survival stratification based on these subtype groupings, underscoring the clinical relevance of the distance-based approach. This reference-centered perspective thus provides a refined lens for dissecting intra-tumor diversity and guiding potential precision oncology strategies.

Chemotherapy serves as the primary therapeutic approach for triple-negative breast cancer (TNBC), yet its efficacy remains unsatisfactory. This study was a single-arm, open-label, single-center clinical trial (NCT05447702) involving patients with newly diagnosed stage II-III TNBC at West China Hospital. The treatment regimen consisted of camrelizumab (200 mg intravenously every 2 weeks, 12 cycles), apatinib (250 mg orally daily), and alternating chemotherapy [nab-paclitaxel (d1, 8, 15 every 4 weeks) for 4 cycles and epirubicin plus cyclophosphamide (every 2 weeks) for 4 cycles]. From June 2023 to April 2024, 35 patients were enrolled, of whom 1 patient withdrew due to adverse reaction intolerance. At treatment completion, the total pathological complete response (tpCR, ypT0/is, ypN0) rate was 67.6% (23/34), and the breast pCR (ypT0/is) rate was 70.6% (24/34). The overall response rate following neoadjuvant treatment reached 94.1% (32/34). Elevated levels of alanine aminotransferase (38.2%) and aspartate aminotransferase (29.4%) were the most common grade 3-4 adverse events, with no significant toxicities or treatment-related deaths reported. Comprehensive analysis of serum and tissue samples collected before and after neoadjuvant therapy via Olink and RNA sequencing revealed that the treatment induced a complex systemic immune response. These findings enabled the development of two novel scoring systems: a pretreatment response predictive score system for stratification and an efficacy assessment score system for treatment response evaluation. In conclusion, camrelizumab and apatinib combined with chemotherapy have good clinical efficacy and good safety as neoadjuvant treatments for stage II-III TNBC, warranting further investigation and potential clinical application.

Esophageal squamous-cell carcinoma (ESCC) is one of the most common gastrointestinal cancers in China, characterized by high malignancy and poor prognosis. Nowadays, the therapeutic options for this cancer are very limited. Notch-signaling is often overactivated in ESCC, but its role remains to be fully elucidated. Here, we demonstrate that aberrant Notch-signaling plays an important role in tumor angiogenesis. In clinical ESCC samples, Notch-signaling activation scores were significantly correlated with tumor microvascular density, advanced TNM stages, and short patient survival time. Silencing Notch-signaling substantially suppressed the ability of ESCC cells to promote angiogenesis in vitro and in vivo. By integrating analysis of CUT&Tag and RNA sequencing data, we identified ubiquitin-specific protease 5 (USP5) as a Notch-signaling downstream effector that is transcriptionally upregulated by the NOTCH1 intracellular domain (NICD1)-RBPJ complex and mediates tumor angiogenesis. USP5 stabilized STAT3 via its deubiquitination function, thereby enhancing the production of pro-angiogenic factors by cancer cells, including VEGF, ANGPT2, and CXCL1. We showed that chemotherapy combined with the USP5 inhibitor can additionally repress tumor growth and angiogenesis in mice. These findings explain why ESCC cells have much fewer NOTCH1 mutations than normal and precancerous epithelium, reveal a novel mechanism for Notch-signaling to drive tumor angiogenesis via the NOTCH1-USP5-STAT3 axis, and open a potential new avenue for anti-tumor angiogenesis therapy.

Radiotherapy is essential in cancer treatment, using ionizing radiation to generate free radicals in the irradiated tissue or to directly damage DNA. Despite comprehensive safety measures, healthy tissue is also irradiated, causing side effects like oral mucositis and dermatitis. Antioxidants, which are known for scavenging free radicals, may reduce these adverse effects, but their impact on radiotherapy efficacy remains unclear. The aim of this systematic review was to evaluate the influence of antioxidant supplementation on radiation-induced side effects, tumor outcome and quality of life. In April 2024, a systematic research was conducted searching five databases (Medline, CINAHL, EMBASE, Cochrane CENTRAL, PsycINFO) to find studies looking at the effect of antioxidant supplementation during radiotherapy on radiation-induced side effects and parameters of tumor outcome or survival. Antioxidants can mitigate radiation-induced side effects, with vitamins C and E showing positive effects on oral mucositis, xerostomia and cardiac function. Curcumin and EGCG improved symptoms such as mucositis, dermatitis and esophagitis, while glutathione-enhanced treatment compliance but did not provide significant protection against side effects. However, multiple studies indicate that the concurrent use of antioxidants during cancer treatment may impair tumor control, increase recurrence rates and reduce survival outcomes. Antioxidants may reduce radiation-induced side effects but could compromise treatment efficacy. Due to inconsistent evidence and potential risks, clinical recommendations are premature. Further high-quality research is needed.

The complex interactions of the tumor micromilieu could be reflected by magnetic resonance imaging (MRI) when analyzed with the radiomics approach. For several tumor entities, it has been shown that radiomics derived from MRI can reflect important characteristics of the tumors. The present study investigated the association radiomics derived from MRI images and histopathological features in uterine cervical cancer.

The MRI before any treatment was used to extract the radiomics features of T1- and T2-weighted images. The biopsy specimens were stained for Ki 67, e-cadherin, vimentin, programmed-death ligand 1, and tumor-infiltrating lymphocytes (TIL, all CD45 positive cells). Tumor-stroma ratio (TSR) was calculated on routine H&E specimen. Spearman's correlation analysis and discrimination analyses were performed as statistical analyses.

The patient sample was comprised of 89 female patients with a mean age of 49.3 years ± 14.6 (range 27-77 years) with squamous cell cervical carcinoma. "Kurtosis" derived from T1-weighted images after contrast media application correlated with the Ki-67 index (r = 0.28, p = 0.02). "WavEnHL_s-4" derived from T2-weighted images and "S(1.0)Contrast" derived from T1-weighted images after contrast media application showed correlations with TSR (r = - 0.24, p = 0.04, each). Several associations were identified between the radiomics features with immune scores defined by programmed-death ligand 1, the highest correlation showed Teta1 derived from T2-weighted images with the combined positive score (r = - 0.38, p < 0.01). There were several associations with vimentin expression, the highest showed "Variance" derived from T1-weighted images after contrast media application (r = 0.46, p < 0.01).

Radiomics features derived from MRI can reflect tumor characteristics of UCC. Especially immune-related features were reflected by the MRI texture features. Proliferation potential, composition of the extracellular matrix and tumor-stroma ratio were also significantly associated with radiomics features. These presented results need to be evaluated in an independent cohort to test their stability.

Discovery of disease-related bacterial biomarkers could be a useful approach for early prevention or diagnosis of various afflictions, such as colorectal cancer. This typically involves analyzing small regions of the 16S rRNA gene (e.g. V3V4) through short-read technologies like Illumina, obtaining genus-level results. However, recent developments in third-generation sequencing, such as Oxford Nanopore Technologies (ONT)'s new R10.4.1 chemistry and its improved basecalling models, are beginning to allow for a more complete and accessible species-level analysis through full-length 16S rRNA gene sequencing (spanning regions V1-V9). Thus, the goal of this study was to compare and evaluate both approaches, using colorectal cancer biomarker discovery as a representative case. This was achieved through the analysis of feces from 123 subjects, comparing both methods (Illumina-V3V4 with DADA2 and QIIME2 vs. ONT-V1V9 with Emu), multiple Dorado basecalling models (fast, hac and sup) and multiple databases (SILVA vs. Emu's Default database). Basecalling models broadly resulted in similar taxonomic output, but had significantly higher observed species and different taxonomic identification the lower the basecalling quality (p-value<0.05). Database choice with Emu influenced the identified species greatly, with Emu's Default database obtaining significantly higher diversity and identified species than SILVA (p-value<0.05). However, it overconfidently classified at times what should be an unknown species as the closest match due to its database structure. Bacterial abundance between Illumina-V3V4 and ONT-V1V9 at the genus level correlated well (R²≥0.8). Nanopore sequencing identified more specific bacterial biomarkers for colorectal cancer than those obtained with Illumina, such as Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis, Peptostreptococcus anaerobius, Gemella morbillorum, Clostridium perfringens, Bacteroides fragilis and Sutterella wadsworthensis. Prediction of colorectal cancer through manual feature selection and machine learning resulted in an AUC of 0.87 with 14 species or 0.82 with just 4 species (P. micra, F. nucleatum, B. fragilis and Agathobaculum butyriciproducens). Full 16S rRNA V1V9 sequencing through Oxford Nanopore and its new R10.4.1 chemistry achieved accurate species-level bacterial identification, facilitating the discovery of more precise disease-related biomarkers and increasing the taxonomic fidelity of future microbiome analyses.

Colorectal cancer (CRC) is both a leading cause of cancer-related mortality and one of the most frequently diagnosed cancers. Previous studies have shown that zearalenone and theabrownin each exert anti-CRC effects. Here, we aimed to evaluate the anti-tumor properties of theabrownin and zearalenone mixture (TZ) and to assess whether supplementing TZ with 5-FU, a commonly used chemotherapeutic drug, could further suppress CRC tumorigenesis. Our results revealed that TZ significantly attenuated AOM/DSS-induced colorectal tumorigenesis. TZ improved survival rate, reduced tumor count, preserved colon length, and mitigated colonic inflammation in AOM/DSS mice. In addition, the concentration of pro-inflammatory cytokines IL-6, TNF-α and IL-17 A/F and proliferative PI3K/AKT were significantly reduced. Metagenomic analyses revealed that TZ modulated the gut microbiota and mycobiota composition and increased the fecal acetate and propionate levels. Furthermore, the enrichment of the bacterial Desulfovibrionaceae bacterium LT0009, Helicobacter sp. MIT 03-1616 and fungal Xylariaceae sp. FL0594 was associated with the reduction of tumor multiplicity and pro-inflammatory cytokines. No additional benefits were observed with combining TZ with 5-FU. Taken together, TZ presented remarkable inhibitory effects on colorectal tumorigenesis, indicating its potential as a novel therapeutic candidate for CRC.

To evaluate the accuracy and acceptability of self-sampling samples for HPV testing for cervical cancer screening in rural Yunnan of China. In 2022, 3000 women aged 17-69 were recruited and provided self-sampling vaginal samples alongside provider-sampling samples for HPV DNA and E6/E7 mRNA testing, as well as artificial intelligence (AI)-assisted cytology. Women who tested positive for any high-risk HPV DNA or mRNA, or who displayed cytology abnormalities, were recalled for a colposcopy examination and biopsied when necessary. The accuracy of these tests in detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2 +) and CIN3 + was evaluated. The sensitivity of the HPV DNA test for self-sampling was 96.2%, compared to 92.3% for provider-sampling, 73.1% for the mRNA test, and 53.9% for AI-assisted cytology in detecting CIN2 + . The specificity was 83.9% for self-sampling HPV DNA test, 86.4% for provider-sampling HPV DNA test, 91.4% for the mRNA test, and 94.2% for AI-assisted cytology. The area under the curve (AUC) values for these screening methods were 0.90, 0.90, 0.82, and 0.74, respectively. Only 37% of participants preferred the self-sampling model, with lower preference observed among older women, those from rare minority groups, those with lower education levels, and who displayed limited knowledge, attitudes, and practices regarding cervical cancer screening. Self-sampling HPV DNA testing demonstrated comparable clinical accuracy to provider-sampling test and were more accurate than that of mRNA test and AI-assisted cytology. Self-sampling HPV testing offers a promising screening strategy in rural Yunnan China. Applicable health education is urgently needed to improve the acceptability of 'self-sampling' model among the target population.

Osteosarcoma is a prevalent primary malignant bone tumor predominantly affecting children and adolescents, characterized by a poor survival rate and prognosis. Currently, ferroptosis is a newly defined form of cell death, but the mechanism between it and osteosarcoma is unclear. To further investigate the relationship between osteosarcoma and ferroptosis, it is important to search for new biomolecular factors. We used bioinformatics to dig deeper into the ferroptosis gene PSAT1, which is closely associated with osteosarcoma. Although PSAT1 has been reported in other types of tumours and plays an important role in the development of many tumours, such as melanoma and breast cancer, little research has been done in the field of osteosarcoma. The results indicated that PSAT1 could promote the development of osteosarcoma and inhibit the ferroptosis process in osteosarcoma cells. This finding implies that PSAT1 may become a new target for the diagnosis and treatment of osteosarcoma in the future, bringing new breakthroughs to clinical practice.