Prognostic Impact of Fusobacterium nucleatum Depends on Combined Tumor Location and Microsatellite Instability Status in Stage II/III Colorectal Cancers Treated with Adjuvant Chemotherapy
2
조회
0
다운로드
4
인용
0
참고문헌
키워드
초록
Background: This study aimed to investigate the prognostic impact of intratumoral Fusobacterium nucleatum in colorectal cancer (CRC) treated with adjuvant chemotherapy. Methods: F. nucleatum DNA was quantitatively measured in a total of 593 CRC tissues retrospectively collected from surgically resected specimens of stage III or high-risk stage II CRC patients who had received curative surgery and subsequent oxaliplatin-based adjuvant chemotherapy (either FOLFOX or CAPOX). Each case was classified into one of the three categories: F. nucleatum–high, –low, or –negative. Results: No significant differences in survival were observed between the F. nucleatum–high and –low/negative groups in the 593 CRCs (p = .671). Subgroup analyses according to tumor location demonstrated that disease-free survival was significantly better in F. nucleatum–high than in –low/negative patients with non-sigmoid colon cancer (including cecal, ascending, transverse, and descending colon cancers; n = 219; log-rank p = .026). In multivariate analysis, F. nucleatum was determined to be an independent prognostic factor in non-sigmoid colon cancers (hazard ratio, 0.42; 95% confidence interval, 0.18 to 0.97; p = .043). Furthermore, the favorable prognostic effect of F. nucleatum–high was observed only in a non-microsatellite instability- high (non-MSI-high) subset of non-sigmoid colon cancers (log-rank p = 0.014), but not in a MSI-high subset (log-rank p = 0.844), suggesting that the combined status of tumor location and MSI may be a critical factor for different prognostic impacts of F. nucleatum in CRCs treated with adjuvant chemotherapy. Conclusions: Intratumoral F. nucleatum load is a potential prognostic factor in a non-MSI-high/non-sigmoid/non-rectal cancer subset of stage II/III CRCs treated with oxaliplatin-based adjuvant chemotherapy.
Abstract
Background: This study aimed to investigate the prognostic impact of intratumoral Fusobacterium nucleatum in colorectal cancer (CRC) treated with adjuvant chemotherapy. Methods: F. nucleatum DNA was quantitatively measured in a total of 593 CRC tissues retrospectively collected from surgically resected specimens of stage III or high-risk stage II CRC patients who had received curative surgery and subsequent oxaliplatin-based adjuvant chemotherapy (either FOLFOX or CAPOX). Each case was classified into one of the three categories: F. nucleatum–high, –low, or –negative. Results: No significant differences in survival were observed between the F. nucleatum–high and –low/negative groups in the 593 CRCs (p = .671). Subgroup analyses according to tumor location demonstrated that disease-free survival was significantly better in F. nucleatum–high than in –low/negative patients with non-sigmoid colon cancer (including cecal, ascending, transverse, and descending colon cancers; n = 219; log-rank p = .026). In multivariate analysis, F. nucleatum was determined to be an independent prognostic factor in non-sigmoid colon cancers (hazard ratio, 0.42; 95% confidence interval, 0.18 to 0.97; p = .043). Furthermore, the favorable prognostic effect of F. nucleatum–high was observed only in a non-microsatellite instability- high (non-MSI-high) subset of non-sigmoid colon cancers (log-rank p = 0.014), but not in a MSI-high subset (log-rank p = 0.844), suggesting that the combined status of tumor location and MSI may be a critical factor for different prognostic impacts of F. nucleatum in CRCs treated with adjuvant chemotherapy. Conclusions: Intratumoral F. nucleatum load is a potential prognostic factor in a non-MSI-high/non-sigmoid/non-rectal cancer subset of stage II/III CRCs treated with oxaliplatin-based adjuvant chemotherapy.
참고문헌 (29)
- Kostic AD, "Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumorimmune microenvironment", Cell Host Microbe, 14, pp.207~215 (2013)
- Rubinstein MR, "Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin", beta-catenin signaling via its FadA adhesin, 2013, pp.14, 195~206
- Mima K, "Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis", Gut, 65, pp.1973~1980 (2016)
- Yu T, "Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy", Cell, 170, pp.548.e16~563.e16 (2017)
- Geller LT, "Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine", Science, 357, pp.1156~1160 (2017)
- Kostic AD, "Genomic analysis identifies association of Fusobacterium with colorectal carcinoma", Genome Res, 22, pp.292~298 (2012)
- Castellarin M, "Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma", Genome Res, 22, pp.299~306 (2012)
- Tahara T, "Fusobacterium in colonic flora and molecular features of colorectal carcinoma", Cancer Res, 74, pp.1311~1318 (2014)
- Ito M, "Association of Fusobacterium nucleatum with clinical and molecular features in colorectal serrated pathway", Int J Cancer, 137, pp.1258~1268 (2015)
- Yu J, "Invasive Fusobacterium nucleatum may play a role in the carcinogenesis of proximal colon cancer through the serrated neoplasia pathway", Int J Cancer, 139, pp.1318~1326 (2016)
- Flanagan L, "Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome", Eur J Clin Microbiol Infect Dis, 33, pp.1381~1390 (2014)
- Mima K, "Fusobacterium nucleatum and T cells in colorectal carcinoma", JAMA Oncol, 1, pp.653~661 (2015)
- Mima K, "Fusobacterium nucleatum in colorectal carcinoma tissue according to tumor location", Clin Transl Gastroenterol, 7, pp.e200~ (2016)
- Park HE, "Intratumoral Fusobacterium nucleatum abundance correlates with macrophage infiltration and CDKN2A methylation in microsatellite-unstable colorectal carcinoma", Virchows Arch, 471, pp.329~336 (2017)
- Routy B, "Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors", Science, 359, pp.91~97 (2018)
- Vetizou M, "Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota", Science, 350, pp.1079~1084 (2015)
- Gopalakrishnan V, "Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients", Science, 359, pp.97~103 (2018)
- Bae JM, "Downregulation of acetyl-CoA synthetase 2 is a metabolic hallmark of tumor progression and aggressiveness in colorectal carcinoma", Mod Pathol, 30, pp.267~277 (2017)
- Boland CR, "A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer", Cancer Res, 58, pp.5248~5257 (1998)
- Yamaoka Y, "Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population", J Gastroenterol, 53, pp.517~524 (2018)
- Stintzing S, "Understanding the role of primary tumour localisation in colorectal cancer treatment and outcomes", Eur J Cancer, 84, pp.69~80 (2017)
- Bae JM, "Molecular subtypes of colorectal cancer and their clinicopathologic features, with an emphasis on the serrated neoplasia pathway", Arch Pathol Lab Med, 140, pp.406~412 (2016)
- Dejea CM, "Microbiota organization is a distinct feature of proximal colorectal cancers", Proc Natl Acad Sci U S A, 111, pp.18321~18326 (2014)
- Abed J, "Fap2 mediates Fusobacterium nucleatum colorectal adenocarcinoma enrichment by binding to tumorexpressed Gal-GalNAc", Cell Host Microbe, 20, pp.215~225 (2016)
- Hamada T, "Fusobacterium nucleatum in colorectal cancer relates to immune response differentially by tumor microsatellite instability status", Cancer Immunol Res, 6, pp.1327~1336 (2018)
- Pagès F, "International validation of the consensus Immunoscore for the classification of colon cancer : a prognostic and accuracy study", Lancet, 391, pp.2128~2139 (2018)
- Lee DW, "Association between Fusobacterium nucleatum, pathway mutation, and patient prognosis in colorectal cancer", Ann Surg Oncol, 25, pp.3389~3395 (2018)
- Kim JH, "Molecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer", World J Gastroenterol, 20, pp.4230~4243 (2014)
- Shang FM, "Fusobacterium nucleatum and colorectal cancer : a review", World J Gastrointest Oncol, 10, pp.71~81 (2018)