Dataset Information

Cross-cancer analysis identifies metastatic-specific intratumoral microbiota signature with Streptococcus spp. as key microbial hub

ABSTRACT: Cancer remains one of the leading global health challenges, with lung (LC), breast (BC), and colorectal (CRC) cancers among the most prevalent and deadly malignancies. The intratumoral microbiota (IM), a distinct microbial ecosystem within tumor tissues, has emerged as a potential modulator of carcinogenesis, immune responses, and metastatic progression; however, comparative cross-cancer analyses are very scarce. In this study, we profiled and compared the IM composition and diversity in FFPE samples from an Italian cohort of BC (GSE212891), CRC (GSE216589), and LC patients. BC samples exhibited the highest genus-level richness, whereas CRC samples showed significantly greater overall alpha diversity, consistent with the microbial complexity of the gut environment. LC samples displayed the most balanced microbial distribution, as indicated by the highest Shannon index value. Stratification by metastatic condition revealed distinct microbial signatures: 16 genera were exclusive to metastatic tumors and 49 to non-metastatic ones. In BC specifically, the class Clostridia and family Burkholderiaceae were enriched in non-metastatic samples, accompanied by distinct functional shifts in pantothenate and coenzyme A biosynthesis and lysine and lipid A pathways. Microbial network analysis further uncovered differences in ecological community structure and keystone taxa: Streptococcus spp. predominated as hubs in metastatic tumors, whereas Neisseria spp. were central in non-metastatic networks. Overall, our findings highlight cancer-type– and metastasis-specific microbial signatures, supporting a potential role for the IM in tumor progression and offering avenues for biomarker development and therapeutic targeting.

ORGANISM(S): Homo sapiens

PROVIDER: GSE304021 | GEO | 2026/05/07

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Lung Cancer (LC), colorectal cancer (CRC) and breast cancer (BC) are the major killers in oncology, accounting for about 40% of cancer deaths. Although progresses have been made in the last few years, unfortunately no patient with metastatic disease can obtain a definitive cure. A recent hypothesis is that cancer is driven by a small subpopulation of cells called "cancer stem cells" (CSCs) or "tumor initiating cells" with an unlimited proliferative potential and the ability to reproduce the original human tumor in experimental animal models. These cells are thought to be responsible for the development of the tumor and represent the only cell population able to sustain tumor growth and progression. Therefore, CSCs represent the elective target for new targeted therapies, endowed with high and selective toxicity towards the tumor but harmless towards normal cells. Current technologies allow us to isolate and expand in vitro the CSCs from tumor specimens, testing their sensitivity to different anticancer drugs in a short period of time. Therefore, there is the potential opportunity to identify LC, CRC and BC CSCs.This is a prospective study assessing feasibility of CSCS isolation in LC, CRC and BC. Patients with a previously performed diagnosis of LC, colon cancer or breast cancer with no further standard therapy options, with a Karnofsky performance status of 100% and with tumor tissue available will be considered eligible for the study. Tumor tissue will be collected before study entry, i.e tissue obtained during a diagnostic or therapeutical procedure, like surgery or biopsies with other purposes than the protocol. In vitro tumor sensitivity to chemotherapy drugs will be tested on tumor cell cultures per each patient. Drugs and their combination will be considered effective and if they kill ≥ 60% of tumor stem cells in vitro test. By using cancer spheres the investigators will also generate orthotopic xenograft models that recapitulate the parental tumor behaviour, including the aggressive features and the invasiveness potential. Orthotopic injection technique will be assessed in 5 weeks-old NOD/SCID mice

Project description:Background: Liver metastasis is the major cause of death following a diagnosis of colorectal cancer (CRC) and is a major health burden. Most molecular studies of CRC have profiled primary tumor samples and not the metastasis samples. In this study, we compared the copy number profiles of matched primary and liver metastatic CRC to better understand how the genomic structure of primary CRC differs from the metastasis. This has important implications for whether it is justified to base therapeutic approaches solely on data from the primary tumour. Methods: Paired primary and metastatic tumours from 16 patients and their adjacent normal tissue samples were analyzed using Single-Nucleotide-Polymorphism (SNP) arrays to determine copy number alterations. Nine patients had a synchronous liver metastasis at the time of CRC diagnosis and 7 patients developed a liver metastasis metachronously. Genome-wide chromosomal copy number alterations were assessed, with particular attention to 189 genes known to be somatically altered in CRC and 25 genes that are clinically actionable in CRC. These data were analyzed with respect to the timing of primary and metastatic tissue resection and with exposure to chemotherapy. Results: The genomic divergence with the whole genome duplication correction applied the average percent copy number discordance across all pairs of samples was 22.02%. The pairs of tumour samples collected prior to treatment revealed a significantly higher copy number differences compared to previously treated liver metastasis samples (P=0.024). However, loss of heterozygosity (LOH) acquired in metastasis was significantly higher in previously treated liver metastasis samples compared to treatment naïve liver metastasis samples (P= 0.0064) and which included where KRAS mutation was present in the primary cancers but was not detectable in the metastatic sample following chemotherapy. With regard to 25 genes that are clinically actionable in CRC, amplification of the genes ERBB2, FGFR1, CDK8 or PIK3CA was observed in the metastatic tissue of 4 patients but not in the matched primary CRC. In these cases, knowledge of these metastatic specific alterations could have informed therapeutic decision making and may have improved patient outcome. Conclusion: Intra-patient genomic discrepancies observed between primary and metastatic tissue

Dataset Information

Cross-cancer analysis identifies metastatic-specific intratumoral microbiota signature with Streptococcus spp. as key microbial hub

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets