Dataset Information

Interaction between intratumoral microbiota and tumor mediates the response of neoadjuvant therapy for rectal cancer.

ABSTRACT:

Background

Previous observations have demonstrated that the response to neoadjuvant chemoradiotherapy (nCRT) is highly variable in patients with locally advanced rectal cancer (LARC). Recent studies focusing on the intratumoral microbiota of colorectal cancer have revealed its role in oncogenesis and tumor progression. However, limited research has focused on the influence of intratumoral microbiota on the nCRT of LARC.

Methods

We explored the microbial profiles in the tumor microenvironment of LARC using RNA-seq data from a published European cohort. Microbial signatures were characterized in pathological complete response (pCR) and non-pCR groups. Multi-omics analysis was performed between intratumor microbiomes and transcriptomes.

Results

Microbial α and β diversity were significantly different in pCR and non-pCR groups. Twelve differential microbes were discovered between the pCR and non-pCR groups, six of which were related to subclusters of cancer-associated fibroblasts (CAFs) associated with extracellular matrix formation. A microbial risk score based on the relative abundance of seven differential microbes had predictive value for the nCRT response (AUC = 0.820, p < 0.001).

Conclusion

Our study presents intratumoral microbes as potential independent predictive markers for the response of nCRT to LARC and demonstrates the underlying mechanism by which the interaction between intratumoral microbes and CAFs mediates the response to nCRT.

SUBMITTER: Sun L

PROVIDER: S-EPMC10602640 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Interaction between intratumoral microbiota and tumor mediates the response of neoadjuvant therapy for rectal cancer.

Sun Lejia L Qu Jiangming J Ke Xindi X Zhang Yue Y Xu Hengyi H Lv Ning N Leng Jingze J Zhang Yanbin Y Guan Ai A Feng Yifei Y Sun Yueming Y

Frontiers in microbiology 20231012

<h4>Background</h4>Previous observations have demonstrated that the response to neoadjuvant chemoradiotherapy (nCRT) is highly variable in patients with locally advanced rectal cancer (LARC). Recent studies focusing on the intratumoral microbiota of colorectal cancer have revealed its role in oncogenesis and tumor progression. However, limited research has focused on the influence of intratumoral microbiota on the nCRT of LARC.<h4>Methods</h4>We explored the microbial profiles in the tumor micro ...[more]

PMID: 37901832

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Project description:BackgroundThe watch-and-wait approach may be safe for selected rectal cancer patients who achieve a complete clinical response after neoadjuvant treatment. Endoscopic examination is critical in determining completeness of tumor response but has not been systematically studied.MethodsTwo cross-sectional surveys, each containing endoscopic photos of rectal cancers treated with neoadjuvant therapy, were distributed to surgeons. The first survey assessed the reproducibility of eight endoscopic criteria using 41 unique endoscopic photos. The percentage of surgeons selecting each of the prespecified endoscopic criteria for each photo was calculated to determine the reproducibility of endoscopic criteria in assessing treatment and tumor response grade across multiple surgeons. The second survey included endoscopic pairs of pre- and post-neoadjuvant treatment photos of 17 patients. The surgeons were assigned a tumor response grade (clinical complete response [cCR], near complete clinical response [nCR], incomplete [iCR] clinical response), and percentages of correct diagnostic assignment were calculated.ResultsThe findings showed significant inter- and intra-surgeon variation in the selection of predefined endoscopic features used to grade tumor response as well as significant inter- and intra-surgeon variation in the selection of the tumor response grade (cCR, nCR, or iCR). However, individual endoscopic features and tumor response grades clustered together, suggesting consistency in tumor response interpretation. Surgeons were more accurate in identifying patients with a complete response (82%) than in identifying patients with an incomplete response (68%).ConclusionsDespite inter- and intra-surgeon variation, endoscopic features were well-selected in terms of tumor response grade, suggesting consistency in endoscopic interpretation. Surgeons tended to underestimate the degree of tumor response, identifying complete responses more accurately than incomplete responses.

Project description:BackgroundNeoadjuvant chemoimmunotherapy (NACI) has emerged as the standard treatment for early-stage triple-negative breast cancer (TNBC). However, reliable biomarkers for identifying patients who are likely to benefit from NACI are lacking. This study aims to develop an intratumoral microbiota-aided radiomics model for predicting pathological complete response (pCR) in patients with TNBC.MethodsIntratumoral microbiota are characterized by 16S rDNA sequencing and quantified through experimental assays. Single-cell RNA sequencing is performed to analyze the tumor microenvironment of tumors with various responses to NACI. Radiomics features are extracted from tumor regions on longitudinal magnetic resonance images (MRIs) scanned before and after NACI in the training set. On the basis of treatment response (pCR or non-pCR) and intratumoral microbiota scoring, we select key radiomics features and construct a fusion model integrating multi-timepoint (pre-NACI and post-NACI) MRI to predict the efficacy of immunotherapy, followed by independent external validation.ResultsA total of 124 patients are enrolled, with 88 in the training set and 36 in the validation set. Tumors from patients who achieves pCR present a significantly greater intratumoral microbiota load than tumors from patients who achieve non-pCR (p < 0.05). Additionally, tumors in non-pCR group exhibit greater infiltration of tumor-associated SPP1+ macrophages, which is negatively correlated with the microbiota load. On the basis of intratumoral microbiota scoring, we select 17 radiomics features and use them to construct the fusion radiomics model. The fusion model achieves the highest AUC of 0.945 in the training set, outperforming pre-NACI (AUC = 0.875) and post-NACI (AUC = 0.917) models. In the validation set, this model maintains a superior AUC of 0.873, surpassing those of pre-NACI (AUC = 0.769) and post-NACI (AUC = 0.802) models. Clinically, the fusion model distinguishes patients who achieve pCR from those who do not with an accuracy of 77.8%. Decision curve analysis demonstrates the superior net clinical benefit of this model across varying risk thresholds.ConclusionsOur intratumoral microbiota-aided radiomics model could serve as a powerful and noninvasive tool for predicting the response of patients with early-stage TNBC to NACI.

Dataset Information

Interaction between intratumoral microbiota and tumor mediates the response of neoadjuvant therapy for rectal cancer.

Background

Methods

Results

Conclusion

Publications

Interaction between intratumoral microbiota and tumor mediates the response of neoadjuvant therapy for rectal cancer.

Similar Datasets

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