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The Pancreatic Microbiome is Associated with Carcinogenesis and Worse Prognosis in Males and Smokers.

ABSTRACT: 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.

SUBMITTER: Chakladar J

PROVIDER: S-EPMC7565819 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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The Pancreatic Microbiome is Associated with Carcinogenesis and Worse Prognosis in Males and Smokers.

Chakladar Jaideep J Kuo Selena Z SZ Castaneda Grant G Li Wei Tse WT Gnanasekar Aditi A Yu Michael Andrew MA Chang Eric Y EY Wang Xiao Qi XQ Ongkeko Weg M WM

Cancers 20200918 9

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 b ...[more]

PMID: 32962112

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Project description:Carbohydrate sulfotransferase 15 (CHST15) synthesizes matrix proteoglycan that regulates various pathogenic mediators and contributes to tissue remodeling and fibrosis during injury. CHST15 has been reported to promote tumor growth and invasion in various types of cancer. Our previous study reported the safety and efficacy of EUS-guided fine-needle injection (EUS-FNI) of STNM01, a double-stranded RNA oligonucleotide that specifically represses CHST15, for use in patients with pancreatic cancer. The present study aimed to determine the expression and clinicopathological characteristics of CHST15 in pancreatic cancer. Immunohistochemical staining was performed for CHST15 using pancreatic tissues from 64 patients (28 males and 36 females; age, 69.0±9.6 years) with pancreatic cancer who underwent surgery. For the evaluation of fibrosis, two categories were defined (mature and immature), based on the existence of collagen, myxoid stroma and fibroblasts, using hematoxylin and eosin specimens. The positive percentage of CHST15 was quantified, patients were divided into two groups according to high and low CHST15 expression in both the cancer and stroma tissues, and the association between CHST15 expression in cancer cells and the stroma was analyzed. Additionally, the present study analyzed the association between CHST15 expression and clinicopathological information, including overall and disease-free survival. The expression levels of CHST15 were detected in the cytoplasm of pancreatic cancer cells and fibroblasts in the cancer stroma. CHST15 expression in cancer cells was not identified to be associated with overall survival (P=0.52). However, patients with high CHST15 expression in the stroma exhibited worse overall survival compared with patients with low CHST15 expression (P=0.02). CHST15 expression in the stroma exhibited a positive association with that in cancer cells (P=0.01). High CHST15 expression in the stroma group was associated with a higher incidence of immature fibrosis (P=0.02) compared with mature fibrosis. CHST15 expression in cancer cells was associated with Union for International Cancer Control stage (P=0.02) and invasive front. Age and sex were not associated with CHST15 expression. The present study revealed that overexpression of CHST15 in stroma was associated with worse overall survival and immature fibrosis. Overexpression of CHST15 in cancer cells was associated with tumor stage. These results suggested that targeting therapy for CHST15 may be useful for stroma fibroblasts and cancer cells.

Dataset Information

The Pancreatic Microbiome is Associated with Carcinogenesis and Worse Prognosis in Males and Smokers.

Publications

The Pancreatic Microbiome is Associated with Carcinogenesis and Worse Prognosis in Males and Smokers.

Similar Datasets

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