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Background: Overweight is known to be an important risk factor for colorectal cancer (CRC), and the differences in intestinal flora among CRC patients with different BMI status have not been clearly defined. The purpose of this study was to elucidate the differences in the abundance, composition and biological function of intestinal flora in CRC patients with different BMI status. Method: A total of 170 CRC patients were included and grouped according to the BMI data of CRC patients. BMI ≥ 24 kg/m2 was defined as overweight group, and BMI within the range of 18.5–23.9 kg/m2 was defined as normal weight group. Preoperative stool collection of patients in both groups was used for 16S rRNA sequencing. Total RNA was extracted from 17 CRC tumor tissue samples for transcriptome sequencing, and then CIBERSORT algorithm was used to convert the transcriptome data into the relative content matrix of 22 kinds of immune cells, and the correlation between different intestinal flora and immune cells and immune-related genes under different BMI states was analyzed. Finally, we identified BMI-related differential functional pathways and analyzed the correlation between these pathways and differential intestinal flora. Result: There was no significant difference in α diversity and β diversity analysis between overweight group and normal weight group. Partial least square discriminant analysis (PLS-DA) could divide the flora into two different clusters according to BMI stratification. A total of 33 BMI-related differential flora were identified by linear discriminant effect size analysis (LEfSe), among which Actinomyces, Desulfovibrio and Bacteroides were significantly enriched in overweight group. ko00514: Other types of O-glycan biosynthesis are significantly enriched in overweight group. There was a significant positive correlation between Clostridium IV and Macrophages M2 and T cells regulatory (Tregs). There was a significant negative correlation with Dendritic cells activated and T cells CD4 memory activated. Conclusions: The richness and diversity of intestinal flora of CRC patients may be related to different BMI status, and the enrichment of Actinomyces, Desulphurvibrio and Bacteroides may be related to overweight status of CRC patients. The tumor microenvironment in which BMI-related differential flora resides has different immune landscapes, suggesting that some intestinal flora may affect the biological process of CRC by regulating immune cell infiltration and immune gene expression, but further experiments are needed to confirm this. [ABSTRACT FROM AUTHOR]

Heat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1 in pan-cancer and comprehensively evaluate HSP90B1 as a novel biomarker that hold promise for precision cancer diagnostics and therapeutics. The results suggest HSP90B1 was highly expressed in various kinds of tumors, often correlating with a poor prognosis. Notably, methylation of HSP90B1 emerged as a protective factor in several cancer types. In immune infiltration analysis, the expression of HSP90B1 in most tumors showed a negative association with CD8 + T cells. HSP90B1 expression was positively correlated with microsatellite instability and tumor mutational burden. HSP90B1 expression was also discovered to be positively correlated with tumor metabolism, cell cycle-related pathways and the expression of immune checkpoint genes. The expression of HSP90B1 was mainly negatively correlated with immunostimulatory genes and positively correlated with immunosuppressive genes, as well as strongly correlated with chemokines and their receptor genes. In addition, the HSP90B1 inhibitor PU-WS13 demonstrated significant efficacy in suppressing cancer cell proliferation in both leukemic and solid tumor cells, and remarkably reduced the expression of the cancer cell surface immune checkpoint PD-L1. The single-cell RNA sequencing analysis further highlighted that HSP90B1 was significantly higher in tumor cells compared to surrounding cells, revealing a potential target therapeutic window. Taken together, HSP90B1 emerges as a promising avenue for breakthroughs in cancer diagnosis, prognosis and therapy. This study provides a rationale for HSP90B1 targeted cancer diagnosis and therapy in future. [ABSTRACT FROM AUTHOR]