Endoscopic ultrasound-guided fine-needle biopsy as a tool for studying the intra-tumoral microbiome in pancreatic ductal adenocarcinoma: a pilot study

Abstract

A new approach by investigating the intra-tumoral microbiome raised great interest because they may influence the host immune response and natural history of the disease. However, previous studies on the intra-tumoral microbiome of pancreatic ductal adenocarcinoma (PDAC) were mostly based on examining the formalin-fixed paraffin-embedded tumor specimens. This study aims to investigate the feasibility of using endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) as a complementary procedure of surgical biopsy to obtain adequate fresh pancreatic cancer tissue for intra-tumoral microbial research. This was a prospective pilot study performed at a single tertiary referral center. We obtained pancreatic cancer tissue by EUS-FNB and surgical biopsy, respectively. We amplified the V3-V4 hyper-variable region of bacterial 16S ribosomal ribonucleic acid (rRNA) genes, constructed a pair-end library, and performed high-throughput sequencing. From August 2020 to November 2020, nine eligible patients with PDAC were enrolled in this study. The intra-tumoral microbiome profile was successfully generated from the PDAC cancer tissue obtained by EUS-FNB as well as by surgical biopsy. There was no significant difference in intra-tumoral alpha-diversity or bacterial taxonomic composition between tissues obtained by EUS-FNB and by surgical biopsy. EUS-FNB can collect sufficient fresh cancer tissue for microbiome analyses without complication. The intra-tumoral microbiome profile in tissues obtained by EUS-FNB had similar alpha-diversity and taxonomic profiles with those obtained by surgical biopsy. It implicated, except for surgical biopsy, EUS-FNB can be another valid and valuable tool for studying intra-tumoral microbiome in patients with resectable and unresectable PDAC.

The Role of Microbiota in Pancreatic Cancer

“…The intrapancreatic microbiota of PC patients, analyzed by Pushalkar and colleagues, revealed a higher presence of Proteobacteria (45%) and Bacteroides (31%), with an increased bacterial abundance compared to healthy controls [5]. A higher concentration of Proteobacteria in the samples from the PC patients was found in a study of 187 patients and in a survey conducted on 1526 samples from different tumor types [46][47][48]. On the other hand, a study conducted by Geller et al suggested an enhanced ability to metabolize chemotherapies due to a higher abundance of Gammaproteobacteria [27,34].…”

Intratumoral microbiota: roles in cancer initiation, development and therapeutic efficacy

“…A study compared the microbiome of pancreatic duct adenocarcinoma samples obtained using endoscopic ultrasound-guided fine-needle aspiration biopsy with those obtained by surgical resection, and the results showed that microorganisms obtained by biopsy were contained within surgically removed samples. 252 The organisms obtained from non-small cell lung cancer broncho alveolar lavage fluid are clearly correlated with intratumoral microbiota, and their classification and abundance can be used to assess the severity of non-small cell lung cancer. 253 Proteobacteria is significantly enriched in the broncho alveolar lavage fluid of non-small cell lung cancer, and further subdivision of the bacterial communities is associated with adenocarcinoma and squamous cell carcinoma respectively.…”