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Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis.

Mitsuhashi K, Nosho K, Sukawa Y, Matsunaga Y, Ito M, Kurihara H, Kanno S, Igarashi H, Naito T, Adachi Y, Tachibana M, Tanuma T, Maguchi H, Shinohara T, Hasegawa T, Imamura M, Kimura Y, Hirata K, Maruyama R, Suzuki H, Imai K, Yamamoto H, Shinomura Y - Oncotarget (2015)

Bottom Line: Fusobacterium species is an oral bacterial group of the human microbiome.We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31.In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023).

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.

ABSTRACT
Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer.

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Related in: MedlinePlus

Kaplan–Meier curves of cancer-specific survival of patients with pancreatic cancer according to CpG island methylator phenotype (CIMP) statusIn the Kaplan–Meier analysis, CIMP-high status significantly correlated with shorter survival (log-rank p = 0.024).
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Figure 4: Kaplan–Meier curves of cancer-specific survival of patients with pancreatic cancer according to CpG island methylator phenotype (CIMP) statusIn the Kaplan–Meier analysis, CIMP-high status significantly correlated with shorter survival (log-rank p = 0.024).

Mentions: In the Kaplan–Meier analysis, high expression levels of miR-21 (log-rank p = 0.0025; Figure 3A), miR-31 (log-rank p = 0.0003; Figure 3B), and CIMP-high status (log-rank p = 0.024; Figure 4) significantly correlated with shorter survival. In contrast, neither KRAS mutations nor miR-143 was associated with patient survival (data not shown).


Association of Fusobacterium species in pancreatic cancer tissues with molecular features and prognosis.

Mitsuhashi K, Nosho K, Sukawa Y, Matsunaga Y, Ito M, Kurihara H, Kanno S, Igarashi H, Naito T, Adachi Y, Tachibana M, Tanuma T, Maguchi H, Shinohara T, Hasegawa T, Imamura M, Kimura Y, Hirata K, Maruyama R, Suzuki H, Imai K, Yamamoto H, Shinomura Y - Oncotarget (2015)

Kaplan–Meier curves of cancer-specific survival of patients with pancreatic cancer according to CpG island methylator phenotype (CIMP) statusIn the Kaplan–Meier analysis, CIMP-high status significantly correlated with shorter survival (log-rank p = 0.024).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4466679&req=5

Figure 4: Kaplan–Meier curves of cancer-specific survival of patients with pancreatic cancer according to CpG island methylator phenotype (CIMP) statusIn the Kaplan–Meier analysis, CIMP-high status significantly correlated with shorter survival (log-rank p = 0.024).
Mentions: In the Kaplan–Meier analysis, high expression levels of miR-21 (log-rank p = 0.0025; Figure 3A), miR-31 (log-rank p = 0.0003; Figure 3B), and CIMP-high status (log-rank p = 0.024; Figure 4) significantly correlated with shorter survival. In contrast, neither KRAS mutations nor miR-143 was associated with patient survival (data not shown).

Bottom Line: Fusobacterium species is an oral bacterial group of the human microbiome.We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31.In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023).

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo, Japan.

ABSTRACT
Recently, bacterial infection causing periodontal disease has attracted considerable attention as a risk factor for pancreatic cancer. Fusobacterium species is an oral bacterial group of the human microbiome. Some evidence suggests that Fusobacterium species promote colorectal cancer development; however, no previous studies have reported the association between Fusobacterium species and pancreatic cancer. Therefore, we examined whether Fusobacterium species exist in pancreatic cancer tissue. Using a database of 283 patients with pancreatic ductal adenocarcinoma (PDAC), we tested cancer tissue specimens for Fusobacterium species. We also tested the specimens for KRAS, NRAS, BRAF and PIK3CA mutations and measured microRNA-21 and microRNA-31. In addition, we assessed epigenetic alterations, including CpG island methylator phenotype (CIMP). Our data showed an 8.8% detection rate of Fusobacterium species in pancreatic cancers; however, tumor Fusobacterium status was not associated with any clinical and molecular features. In contrast, in multivariate Cox regression analysis, compared with the Fusobacterium species-negative group, we observed significantly higher cancer-specific mortality rates in the positive group (p = 0.023). In conclusion, Fusobacterium species were detected in pancreatic cancer tissue. Tumor Fusobacterium species status is independently associated with a worse prognosis of pancreatic cancer, suggesting that Fusobacterium species may be a prognostic biomarker of pancreatic cancer.

Show MeSH
Related in: MedlinePlus