GUT: What kind of flora contributes to the poor prognosis of patients with colorectal cancer?

Colorectal cancer (CRC) is one of the cancers with the highest morbidity and mortality among solid tumors, and its incidence has steadily increased in recent years, accounting for approximately 10% of newly diagnosed cancer cases worldwide
.

CRC patients with similar macroscopic clinicopathological characteristics show a high degree of heterogeneity at the molecular level, which leads to heterogeneous and often suboptimal treatment responses

Colorectal cancer diagnosis and management

Subgroup strategies, such as consensus molecular subtype ( CMS ) and colorectal cancer intrinsic subtype ( CRIS ), can divide patients into subgroups with more homogenized signal characteristics based on key transcriptome data
.

Among the four subtypes identified by CMS grouping, CMS4 patients have high stromal infiltration, while angiogenesis and transforming growth factor-β (TGF-β) signals are up-regulated, showing poor recurrence-free and overall survival rates

Subgroup strategies, such as consensus molecular subtype ( CMS ) and colorectal cancer intrinsic subtype ( CRIS ), can divide patients into subgroup strategies with more homogenized signal characteristics based on key transcriptome data .

Recent studies have found that the microbiome plays a key role in health and disease (including cancer)
.

Multiple research groups have shown that the Fusobacteriales (mainly from Fusobacterium nucleatum , Fn ) content in tumor tissues is higher than that in the matched adjacent mucosa , indicating that it plays a pathogenic role in the progression of CRC

Compared with the matched adjacent mucosa, the Fusobacteriales strains (mainly from Fusobacterium nucleatum , Fn ) in the tumor tissue have a higher content.

To this end, the researchers explored the relationship between the prevalence of Fn/Fusobacteriales, CMS/CRIS subtypes, cell type composition, immune infiltration, and host background to improve patient stratification and identify specific vulnerabilities that can be treated with drugs
.

immunity

The researchers compared the cell culture experiment with two independent cohorts of colorectal cancer patients (Taxonomy cohort: n=140; Colon and rectal cases in The Cancer Genome Atlas (TCGA-COAD-READ) cohort: n=605) of Fn/ The prevalence of Fusobacteriales is combined with the characteristics of host biology/microvirus
.

Among CRC patients in the Taxonomy and TCGA-COAD-READ CRC cohorts, the abundance of Fn/Fusobacteriales is related to inflammation and immunosuppression
.

Among CRC patients in the Taxonomy and TCGA-COAD-READ CRC cohorts, the abundance of Fn/Fusobacteriales is related to inflammation and immunosuppression
.

Among CRC patients in the Taxonomy and TCGA-COAD-READ CRC cohorts, the abundance of Fn/Fusobacteriales is related to inflammation and immunosuppression

Fn infection through NFkB/TNFα induces inflammation Fn infection through NFkB/TNFα induces inflammation infection High Fn/Fusobacteriales were found in CMS1, microsatellite unstable tumors, which have infiltration of M1 macrophages, M2 macrophages The decrease of interleukin (IL)-6/IL-8/IL-1β signal increased Fn/Fusobacteriales in CMS1, microsatellite unstable tumors, which have infiltration of M1 macrophages, Decrease of M2 macrophages, increase of interleukin (IL)-6/IL-8/IL-1β signal

The analysis of the Taxonomy cohort showed that although the Fn load of CMS4/CRIS-B patients was lower than that of CMS1 patients, Fn had a certain influence on the prognosis of CMS4/CRIS-B patients
.

In the TCGA-COAD-READ cohort, when stratifying patients into interstitial (CMS4 and/or CRIS-B) and non-interstitial (neither CMS4 nor CRIS-B), the researchers also found that Fusobacteriales There are different correlations between relative abundance and results

For patients with stromal tumors and high Fusobacteriales, the risk of exacerbation is about twice

Therefore, the study identified CMS4/CRIS-B patients with a high incidence of Fn/Fusobacteriales as a high-risk subgroup and found that they may benefit from treatments aimed at interstitial biology

 

Original source:

Original source:

Manuela Salvucci et al.

Manuela Salvucci et al.

 

Leave a message here