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As we all know, cells are the basic of the human body, but the number of microorganisms in the human body is more than the total number of cells, they colonize a large number of organs such as the gastrointestinal tract, oral cavity and skin, forming a delicate symbiotic relationship with the human body: or promote health; or cause disease, including tumorigenesis
.
Previously, scientists have detected microbes in many types of cancer, including those in organs previously thought to be sterile, such as the pancreas
.
However, the underlying mechanisms by which microbes influence human tumorigenesis or anti-tumor responses remain elusive
.
In a new study published in Cancer Cell, a team of researchers from Rutgers Center for Advanced Biotechnology and Medicine and Rutgers Cancer Research Institute has developed a single-cell analysis of host-microbiome interactions to identify somatic cell-associated bacteria in a subset of tumors, and the presence of these cell-associated bacteria predicts a worse prognosis
.
The study provides new insights
into why specific tumors are difficult to treat.
At present, pancreatic cancer is one of the most common malignant tumors of the digestive tract, and it is known as the "king of cancer" because it is difficult to treat and has a very poor prognosis
.
In the new study, the team sought to explore whether microbes are present in pancreatic tumors and whether they have an impact
on cancer progression or treatment.
Recent studies have found that bacteria and fungi can metastasize to the pancreas and induce local and systemic changes, thereby promoting the development of pancreatic ductal adenocarcinoma (PDA); The microbiome in the PDA may also develop resistance to treatment; In addition, increasingly diverse microbiomes and tumor neoantigens
homologous to microbial peptides were detected in tumors from long-term PDA survivors.
However, studying microbes in tumors is difficult, partly because microbiome composition varies widely between individuals, and few model systems can adequately reproduce tumor-microbiome interactions in humans; Moreover, the footprint of microorganisms is too small to be reliably detected
.
To this end, the team developed the Single-Cell Analysis of Host-Microbiome Interactions (SAHMI) approach, a "pipeline"
for systematically recovering and denoiseling microbial signals in human clinical tissues and assessing host-microbiome interactions at single-cell resolution.
Using sophisticated software, they screened through millions of RNA sequences, identifying which might represent human genes and which came from microbes
.
In the study, the researchers demonstrated the utility of SAHMI
.
First, they wanted to determine whether microbial sequences could be detected in human pancreatic ductal adenotumors using scRNA-seq and how their profiles could be compared
to those using different sequencing methods.
The researchers analyzed 4 tumors using scRNA-seq and whole genome sequencing (WGS), and 14 tumors and normal adjacent tissues
with RNA-seq and 16S-rDNA-seq.
Bacteria were detected in all samples and were significantly correlated with bacterial profiles determined using two sequencing techniques.
Subsequently, they studied two large independent cohorts of pancreatic tumors, where microbes were detected in 48 (87 percent) of the 55 pancreas samples, some of which were present with bacteria associated with specific types of cells that were essentially absent in normal pancreatic tissue
.
The presence of these bacteria is associated with cell type-specific gene expression and pathway activity, including cell motility and immune signaling
.
The most common bacteria in both cohorts are Campylobacter spp.
, which are known to cause gastrointestinal and systemic inflammation; others include F.
nucleatum, which is strongly associated with tumorigenesis in colorectal cancer, and oral microbial ciliates (Leptotrichia) associated with pancreatic cancer spp.
) and the enteric pathogen Clostridium difficile associated with pancreatic pathology
.
These bacteria are mainly located within tumor cells, and their abundance is linked to
tumor-associated cellular activity.
The findings contain microbiome-specific features that predict the progression and poor prognosis
of malignancy.
The microbial footprint inside pancreatic tumors raises the question of whether the immune cells present in the body respond to
cancer or microbes.
The findings suggest that the immune response targets the microbes in the tumor, not the cancer cells
.
Together, these findings provide new insights into why pancreatic cancer is difficult to treat, and a better understanding of these interactions could help develop new treatments
for this difficult-to-treat cancer.
.
Previously, scientists have detected microbes in many types of cancer, including those in organs previously thought to be sterile, such as the pancreas
.
However, the underlying mechanisms by which microbes influence human tumorigenesis or anti-tumor responses remain elusive
.
In a new study published in Cancer Cell, a team of researchers from Rutgers Center for Advanced Biotechnology and Medicine and Rutgers Cancer Research Institute has developed a single-cell analysis of host-microbiome interactions to identify somatic cell-associated bacteria in a subset of tumors, and the presence of these cell-associated bacteria predicts a worse prognosis
.
The study provides new insights
into why specific tumors are difficult to treat.
At present, pancreatic cancer is one of the most common malignant tumors of the digestive tract, and it is known as the "king of cancer" because it is difficult to treat and has a very poor prognosis
.
In the new study, the team sought to explore whether microbes are present in pancreatic tumors and whether they have an impact
on cancer progression or treatment.
Recent studies have found that bacteria and fungi can metastasize to the pancreas and induce local and systemic changes, thereby promoting the development of pancreatic ductal adenocarcinoma (PDA); The microbiome in the PDA may also develop resistance to treatment; In addition, increasingly diverse microbiomes and tumor neoantigens
homologous to microbial peptides were detected in tumors from long-term PDA survivors.
However, studying microbes in tumors is difficult, partly because microbiome composition varies widely between individuals, and few model systems can adequately reproduce tumor-microbiome interactions in humans; Moreover, the footprint of microorganisms is too small to be reliably detected
.
To this end, the team developed the Single-Cell Analysis of Host-Microbiome Interactions (SAHMI) approach, a "pipeline"
for systematically recovering and denoiseling microbial signals in human clinical tissues and assessing host-microbiome interactions at single-cell resolution.
Using sophisticated software, they screened through millions of RNA sequences, identifying which might represent human genes and which came from microbes
.
In the study, the researchers demonstrated the utility of SAHMI
.
First, they wanted to determine whether microbial sequences could be detected in human pancreatic ductal adenotumors using scRNA-seq and how their profiles could be compared
to those using different sequencing methods.
The researchers analyzed 4 tumors using scRNA-seq and whole genome sequencing (WGS), and 14 tumors and normal adjacent tissues
with RNA-seq and 16S-rDNA-seq.
Bacteria were detected in all samples and were significantly correlated with bacterial profiles determined using two sequencing techniques.
Subsequently, they studied two large independent cohorts of pancreatic tumors, where microbes were detected in 48 (87 percent) of the 55 pancreas samples, some of which were present with bacteria associated with specific types of cells that were essentially absent in normal pancreatic tissue
.
The presence of these bacteria is associated with cell type-specific gene expression and pathway activity, including cell motility and immune signaling
.
The most common bacteria in both cohorts are Campylobacter spp.
, which are known to cause gastrointestinal and systemic inflammation; others include F.
nucleatum, which is strongly associated with tumorigenesis in colorectal cancer, and oral microbial ciliates (Leptotrichia) associated with pancreatic cancer spp.
) and the enteric pathogen Clostridium difficile associated with pancreatic pathology
.
These bacteria are mainly located within tumor cells, and their abundance is linked to
tumor-associated cellular activity.
The findings contain microbiome-specific features that predict the progression and poor prognosis
of malignancy.
The microbial footprint inside pancreatic tumors raises the question of whether the immune cells present in the body respond to
cancer or microbes.
The findings suggest that the immune response targets the microbes in the tumor, not the cancer cells
.
Together, these findings provide new insights into why pancreatic cancer is difficult to treat, and a better understanding of these interactions could help develop new treatments
for this difficult-to-treat cancer.
Links to papers:
https://doi.
org/10.
1016/j.
ccell.
2022.
09.
009
