Abstract
Simple SummaryThe cancer microbiome has been suggested to be closely involved in the immune dysregulation that leads to carcinogenesis. Given that pancreatic adenocarcinoma (PAAD) is one of the most lethal cancers, it is important to identify features of the microbiome that may contribute to more deadly PAAD tumors. In this study, we analyzed PAAD patient RNA-sequencing data from The Cancer Genome Atlas (TCGA) to correlate abundance of intra-pancreatic microbes to dysregulation of immune and cancer-associated genes and pathways. We discovered that the presence of several bacteria species within PAAD tumors is linked to metastasis and immune suppression. Furthermore, we found that the increased prevalence and poorer prognosis of PAAD in males and smokers are linked to the presence of potentially cancer-promoting or immune-inhibiting microbes. Further study into the roles of these microbes in PAAD is imperative for understanding how a pro-tumor microenvironment may be treated to limit cancer progression.An intra-pancreatic microbiota was recently discovered in several prominent studies. Since pancreatic adenocarcinoma (PAAD) is one of the most lethal cancers worldwide, and the intratumor microbiome was found to be a significant contributor to carcinogenesis in other cancers, this study aims to characterize the PAAD microbiome and elucidate how it may be associated with PAAD prognosis. We further explored the association between the intra-pancreatic microbiome and smoking and gender, which are both risk factors for PAAD. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to infer microbial abundance, which was correlated to clinical variables and to cancer and immune-associated gene expression, to determine how microbes may contribute to cancer progression. We discovered that the presence of several bacteria species within PAAD tumors is linked to metastasis and immune suppression. This is the first large-scale study to report microbiome-immune correlations in human pancreatic cancer samples. Furthermore, we found that the increased prevalence and poorer prognosis of PAAD in males and smokers are linked to the presence of potentially cancer-promoting or immune-inhibiting microbes. Further study into the roles of these microbes in PAAD is imperative for understanding how a pro-tumor microenvironment may be treated to limit cancer progression.
Highlights
Pancreatic cancer is the 12th most common cancer and is highly lethal
To ensure that the microbiota extracted from The Cancer Genome Atlas (TCGA) data did not Cancers 2020,contaminants, 12, x FOR PEER REVIEWrigorous methods were used to correct for potential
To ensure that the microbiota extracted from The Cancer Genome Atlas (TCGA) data did not as the total number microbe reads sequenced increases are likely as contaminants includeofenvironmental contaminants, rigorous methods were used tocontaminants, correct for potential contamination
Summary
Pancreatic cancer is the 12th most common cancer and is highly lethal. The overall 5-year survival rate across all stages of pancreatic adenocarcinoma (PAAD) is 9%, only 3% of patients with metastatic disease are alive after 5 years. PAAD is usually detected at an advanced stage, and most treatment regimens are ineffective, while current interventions to prevent, diagnose, and treat are not satisfactory, leading to the poor overall prognosis [1,2,3,4,5]. Acquired immune evasion, which is comprised of an immunosuppressive microenvironment, poor T cell infiltration, and a low mutational burden, is a dynamic entity connected to immune system control. Based on the special pathological traits of pancreatic cancer, novel strategies such as stoma-targeting therapy, immunotherapy, and neoantigen vaccines are emerging as treatments. These therapies face the challenge of overcoming the highly immunosuppressive tumor microenvironment in pancreatic cancer [7,8,9]
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