Summary Hypoxia is serving crucial roles in cancers. This study aims to comprehensively analyze the molecular features and clinical relevance of a well-defined hypoxia-associated signature in pan-cancer using multi-omics data. Data were acquired from TCGA, CCLE, GDSC, and GEO. RNA expression pattern, copy number variation (CNV), methylation, and mutation of the signature were analyzed. The majority of the 15 genes were upregulated in cancer tissues compared with normal tissue, and RNA expression was negatively associated with methylation level. CNV occurred in almost all the cancers, whereas mutation frequency was low across different cancer types. The signature was also closely related to cancer hallmarks and cancer-related metabolism pathways. NDRG1 was upregulated in kidney cancer tissues as indicated by immunohistochemistry. Besides, most of the 15 genes were risk factors for patients' overall survival. Our results provide a valuable resource that will guide both mechanistic and therapeutic analyses of the hypoxia signature in cancers.

Colorectal cancer(CRC) is the third most frequent malignant tumor. The gut microbiome acts as a vital component of CRC etiology. Fusobacterium nucleatum(Fn) is a key member of colorectal cancer-associated bacteria. But we lack a systematic and in-depth understanding on its role in CRC evolution. In this article, We reviewed the abundance changes and distribution of Fn in CRC occurrence and development, potential effect of Fn in the initiation of CRC, the source of intratumoral Fn and the cause of its tropism to CRC. In addition, We described the mechanism by which Fn promotes the malignant biological behavior of CRC, affects CRC response to therapy, and shapes the tumor immune microenvironment in great detail. Based on the relationship between Fn and CRC, we proposed strategies for CRC prevention and treatment, and discussed the feasibility and limitations of specific cases, to gain insights into further basic and clinical research in the future.

Colorectal cancer (CRC) is the third most common malignant cancer worldwide with the second highest mortality. Gut microbiota can educate the tumor microenvironment (TME), consequently influencing the efficacy of immune checkpoint inhibitors (ICIs). Fusobacterium nucleatum is one of the most crucial bacteria contributing to colorectal tumorigenesis, but the molecular mechanisms between F. nucleatum and TME or ICIs are poorly investigated. In the present study, we firstly analyzed differentially expressed genes and the biological functions between F. nucleatum-infected and uninfected CRC cell lines, with the findings that CCL22 mRNA expression was markedly upregulated after F. nucleatum infection. Moreover, the survival analysis showed that CCL22 was significantly associated with the overall survival of CRC patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis suggested that CCL22 was related to immune-related terms. Furthermore, the ESTIMATE analysis indicated that the high-CCL22-expression subgroup had a higher immune/stromal/estimate score and lower tumor purity. The CIBERSORT analysis indicated that the high-CCL22-expression group had more immune-suppressive cells and less antitumor immune cells. In addition, immune checkpoint genes and cytotoxic genes were positively correlated with CCL22 expression. The immunophenoscore analysis suggested that CCL22 was associated with the IPS-CTLA4 and PD1/PD-L1/PD-L2 score. Interestingly, CCL22 expression in the KRAS and APC mutation groups was markedly reduced compared to that of the wild groups. In summary, our study provided evidence that CCL22 might play a crucial role in F. nucleatum-related colorectal tumorigenesis and correlate with TME and ICIs, which deserves further study.

Colorectal cancer (CRC) is a lethal and common malignancy worldwide. Non-coding (nc)RNAs have been shown to modulate tumor progression in several types of cancer. The present study aimed to investigate the role of hsa_circ_0000212 in CRC, as a sponge of microRNA (miR)-491. The expression levels of miR-491 and forkhead box P4 (FOXP4) were analyzed using data from The Cancer Genome Atlas. The association between miR-491 and FOXP4 and the clinicopathological characteristics were also analyzed. A novel circular (circ)RNA, hsa_circ_0000212, was found to sponge miR-491 based on bioinformatics analysis. The potential binding site between miR-491 and FOXP4 or circ-0000212 was validated using luciferase and RNA immunoprecipitation assays. The expression levels and distribution of circ-0000212 was also determined. Cell Counting Kit-8 and colony formation assays were performed to determine the role of miR-491 or circ-0000212 on the proliferation of the CRC cells. Decreased miR-491 or increased FOXP4 expression levels were associated with the pathological stage in patients with CRC. In addition, miR-491 inhibited cell proliferation by targeting FOXP4. circ-0000212 was increased in CRC tissues and was predominantly localized in the cytoplasm. Furthermore, circ-0000212 augmented viability of the CRC cells by sponging miR-491 and modulating FOXP4. In conclusion, circ-0000212 may serve as a novel tumor-promoter and drug target in CRC.

Background N6-methyladenosine (m 6 A) modification has been widely studied in various cancers, and m 6 A regulators, such as METTL3, METTL14, WTAP, and YTHDF1, play crucial roles in breast cancer. However, a comprehensive study of m 6 A regulators in breast cancer is still lacking. Material/Methods Expression data of m 6 A regulators and clinicopathological information were acquired from The Cancer Genome Atlas (TCGA) program. Protein interaction was collected from the STRING database. Data on tumor purity and correlation among m 6 A regulators were obtained from the TIMER database. LASSO, consensus clustering, and gene set enrichment analysis (GSEA) were used to evaluate the role of m 6 A regulators. Moreover, the prognostic value of m 6 A-related genomic targets in breast cancer was analyzed by Kaplan-Meier analysis and Cox regression models. Results We found most m 6 A regulators were associated with key clinicopathological parameters, such as tumor staging, Nottingham prognostic index (NPI), and cellularity. Also, consensus clustering analysis-based grouping could effectively predict patients’ overall survival. Correlation analysis also showed that these regulators interacted with each other. Patients were further split into a high-risk group and low-risk group based on Cox and LASSO analysis. High-risk patients had a significantly worse overall survival than did low-risk patients. Moreover, AKT1 and MYC were enriched in patients in the high-risk group, according to GSEA analysis. The patients in the high-risk group also displayed resistance to chemoradiotherapy or hormone therapy. Conclusions The m 6 A regulators are critical participants in the development and progression of breast cancer and are likely to be used to predict prognosis and develop treatment strategies.