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Microbiome and metabolome patterns centered on cancer cachexia link skeletal muscle and adipose tissue depletion to clinical outcomes in locally advanced rectal cancer

ABSTRACT:

This study employed untargeted serum metabolomics to delineate the specific metabolic landscape of cancer cachexia in patients with locally advanced rectal cancer. By analyzing LC-MS raw data from 133 patients (64 discovery, 69 validation), we identified and validated key cachexia-associated metabolites, including lithocholic acid and cortisone. These metabolites were closely linked to gut microbial dysbiosis and loss of skeletal muscle and adipose tissue, collectively defining a cachexia-associated gut microbiome–metabolome–host tissue axis. This dataset provides essential molecular-level support for understanding the metabolic basis of cachexia and its inter-individual heterogeneity in clinical outcomes.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS13787 | MetaboLights | 2026-05-09

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS13787_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	a_MTBLS13787_LC-MS_positive_reverse-phase_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13787_LC-MS_negative_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS13787_LC-MS_positive_reverse-phase_metabolite_profiling_v2_maf.tsv	Tabular

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Project description:Background: MicroRNAs (miRNAs) are small, non-coding, RNA molecules which regulate numerous cellular processes. Specific miRNA may be abnormally down-regulated or up-regulated in colorectal cancer and have been found associated with prognosis or response to treatments. However, no study has ever addressed their predictive role in rectal cancer. Therefore, we used microarray technology and RT-PCR to profile miRNA expression patterns in patients (pts) with rectal cancer, with the aim to identify a specific M-bM-^@M-^\signatureM-bM-^@M-^] associated with pathological complete response after neoadjuvant chemo-radiotherapy. Methods: 38 pts with locally advanced rectal cancer (cT3-4/N+) were treated with capecitabine-oxaliplatin and pelvic conformal radiotherapy (45 cGy) followed by surgery (after 6-8 weeks). Pathologic response was scored according to the tumor regression grade (TRG) scale. MiRNA expression profile was analysed by microarray on fresh frozen biopsies obtained before treatment start and confirmed by RT-PCR. The correlation between miRNA expression profile and the TRG coded as TRG1 (pathologic Complete Response-pCR) versus TRG >1 (no pCR) was assessed by statistical analysis methods specifically designed for this study. Findings: 14 miRNAs were selected by arrays analysis as differentially expressed in TRG1 pts and 13 were confirmed by RT-PCR. In particular, 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909*, miR-630 and miR-765) were significantly up-regulated in TRG1 pts, while 2 miRNAs were under -expressed (miR-1274b and miR-720). miR-622 and miR-630 showed 100% sensitivity and specificity in selecting TRG1 cases and were significantly correlated with EGFR (M-OM-^G2=11M-bM-^@M-"793; p= 0M-bM-^@M-"001) and TS expression (M-OM-^G2=10M-bM-^@M-"589; p= 0M-bM-^@M-"001). Interpretation: A set of 13 miRNAs is strongly associated with pathologic complete response and may represent a specific marker of response to chemo-radiotherapy in locally advanced rectal cancer. Experiments were performed on purified RNA from preoperatory biopsies of 38 patients with histological diagnosis of rectal adenocarcinoma invading through the intestinal wall and/or with pelvic lymph node involvement as evaluated by endorectal ultrasonography (uT3-T4 and/or uN+). Patients were treated with neoadjuvant chemo-radiotherapy (capecitabine + oxaliplatin in combination with 45 Gy of pelvic conformal radiotherapy). Patients have been divided in the following two groups: group A those who had obtained a pathologic complete response M-bM-^@M-^S TRG 1, including the patient without detectable disease who refused surgery, group B any pathologic response other than complete.

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Microbiome and metabolome patterns centered on cancer cachexia link skeletal muscle and adipose tissue depletion to clinical outcomes in locally advanced rectal cancer

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