Where Ideas Grow

Microbes & Cancer

ABOUT

Microbes are a well-established cause of cancer and over 15% of the cancer cases worldwide are attributable to microbial agents. Our long-term goal is to understand the pathogenesis of cancers mediated by microbial agents, and to contribute knowledge to develop improved strategies for prevention and early diagnosis of cancer, based on the properties of the microbes.

 

RESEARCH

In the last few years, we have successfully been using Helicobacter pylori infection and gastric cancer as a study model of microbe-associated cancer. Our results have contributed to the current view that progression towards cancer depends on the combined effects of host susceptibility and bacterial virulence factors. We have shown that infection with specific H. pylori virulence-associated genotypes increases the levels of gastric inflammation and epithelial damage, and the risk for gastric atrophy, intestinal metaplasia, and gastric cancer. We have also identified the bacterial virulence factors and the host cell signalling pathways involved in H. pylori-mediated alterations in cell-cell adhesion and cell invasion. More recently, we have been exploring the relationship between the gastric microbiome and gastric carcinogenesis.
Our research relies on well-characterized patient cohorts, in vitro and in vivo models of infection and cancer, allied to microbiology, molecular and cellular biology, next-generation sequencing, and bioinformatics.

 

Current Projects

H2020-SC1-2018-825832 – CeLac & European consortium for a personalized medicine approach to gastric cancer (LEGACy)
POCI-01-0145-FEDER-032532 – Microbiome-derived metabolites as new gastric cancer biomarkers (MALIGN)
NORTE-01-0145-FEDER-000029 – Advancing cancer research: from basic knowledge to application

Immunohistochemistry of a human gastric mucosa infected with H. pylori (dark-brown; top left); principal coordinates analysis (PCoA) plot of gastric microbiome samples (top right); immunofluorescence analysis of a gastric cell line (bottom left); negative staining of H. pylori membrane vesicles (bot

Team

Selected Publications

Ferreira R.M., Pereira-Marques J., Pinto-Ribeiro I., Costa J.L., Carneiro F., MacHado J.C., Figueiredo C.,
Gastric microbial community profiling reveals a dysbiotic cancer-associated microbiota. Gut67(2):226-236, 2018. [Journal: Article] [CI: 404] [IF: 17,9]
DOI: 10.1136/gutjnl-2017-314205 SCOPUS: 85043251326

Rajilic-Stojanovic M., Figueiredo C., Smet A., Hansen R., Kupcinskas J., Rokkas T., Andersen L., Machado J.C., Ianiro G., Gasbarrini A., Leja M., Gisbert J.P., Hold G.L.,
Systematic review: gastric microbiota in health and disease. Alimentary Pharmacology and Therapeutics51(6):582-602, 2020. [Journal: Review] [CI: 97] [IF: 8,2]
DOI: 10.1111/apt.15650 SCOPUS: 85079728677

Pereira-Marques J., Hout A., Ferreira R.M., Weber M., Pinto-Ribeiro I., Van Doorn L.J., Knetsch C.W., Figueiredo C.,
Impact of host DNA and sequencing depth on the taxonomic resolution of whole metagenome sequencing for microbiome analysis. Frontiers in Microbiology10(JUN):, 2019. [Journal: Article] [CI: 95] [IF: 4,2]
DOI: 10.3389/fmicb.2019.01277 SCOPUS: 85069196942

Marques M.S., Melo J., Cavadas B., Mendes N., Pereira L., Carneiro F., Figueiredo C., Leite M.,
Afadin downregulation by helicobacter pyloriInduces epithelial to mesenchymal transition in gastric cells. Frontiers in Microbiology9(NOV):, 2018. [Journal: Article] [CI: 19] [IF: 4,3]
DOI: 10.3389/fmicb.2018.02712 SCOPUS: 85056637997

Figueiredo C., Constanza Camargo M., Leite M., Fuentes-Pananá E.M., Rabkin C.S., Machado J.C.,
Pathogenesis of gastric cancer: Genetics and molecular classification. Current Topics in Microbiology and Immunology400:277-304, 2017. [Book Series: Book Chapter] [CI: 97] [IF: 5,8]
DOI: 10.1007/978-3-319-50520-6_12 SCOPUS: 85010908079

Ferreira R.M., Pinto-Ribeiro I., Wen X., Marcos-Pinto R., Dinis-Ribeiro M., Carneiro F., Figueiredo C.,
Helicobacter pylori cagA promoter region sequences influence CagA expression and interleukin 8 secretion. Journal of Infectious Diseases213(4):669-673, 2016. [Journal: Article] [CI: 37] [IF: 6,3]
DOI: 10.1093/infdis/jiv467 SCOPUS: 84960172758

Costa A.M., Ferreira R.M., Pinto-Ribeiro I., Sougleri I.S., Oliveira M.J., Carreto L., Santos M.A., Sgouras D.N., Carneiro F., Leite M., Figueiredo C.,
Helicobacter pylori activates matrix metalloproteinase 10 in gastric epithelial cells via EGFR and ERK-mediated pathways. Journal of Infectious Diseases213(11):1767-1776, 2016. [Journal: Article] [CI: 41] [IF: 6,3]
DOI: 10.1093/infdis/jiw031 SCOPUS: 84978646526

Paredes J., Figueiredo J., Albergaria A., Oliveira P., Carvalho J., Ribeiro A.S., Caldeira J., Costa A.M., Simões-Correia J., Oliveira M.J., Pinheiro H., Pinho S.S., Mateus R., Reis C.A., Leite M., Fernandes M.S., Schmitt F., Carneiro F., Figueiredo C., Oliveira C., Seruca R.,
Epithelial E- and P-cadherins: Role and clinical significance in cancer. Biochimica et Biophysica Acta - Reviews on Cancer1826(2):297-311, 2012. [Journal: Review] [CI: 175] [IF: 9]
DOI: 10.1016/j.bbcan.2012.05.002 SCOPUS: 84861800037

Ferreira R.M., Machado J.C., Letley D., Atherton J.C., Pardo M.L., Gonzalez C.A., Carneiro F., Figueiredo C.,
A novel method for genotyping the Helicobacter pylori vacA intermediate region directly in gastric biopsy specimens. Journal of Clinical Microbiology50(12):3983-3989, 2012. [Journal: Article] [CI: 39] [IF: 4,1]
DOI: 10.1128/JCM.02087-12 SCOPUS: 84869213164

Ferreira R.M., Figueiredo C., Bonet C., Pardo M.L., Liso J.M.R., Alonso P., Sala N., Capella G., Sanz-Anquela J.M., González C.A.,
Helicobacter pylori vacA intermediate region genotyping and progression of gastric preneoplastic lesions. American Journal of Gastroenterology107(1):145-146, 2012. [Journal: Letter] [CI: 13] [IF: 7,6]
DOI: 10.1038/ajg.2011.389 SCOPUS: 84855428342

Leite M., Figueiredo C.,
A method for short-term culture of human gastric epithelial cells to study the effects of helicobacter pylori. Methods in Molecular Biology921:61-68, 2012. [Book Series: Article] [CI: 3]
DOI: 10.1007/978-1-62703-5-2_9 SCOPUS: 84934434604

González C.A., Figueiredo C., Lic C.B., Ferreira R.M., Pardo M.L., Ruiz Liso J.M., Alonso P., Sala N., Capella G., Sanz-Anquela J.M.,
Helicobacter pylori cagA and vacA genotypes as predictors of progression of gastric preneoplastic lesions: A long-term follow-up in a high-risk area in Spain. American Journal of Gastroenterology106(5):867-874, 2011. [Journal: Article] [CI: 108] [IF: 7,3]
DOI: 10.1038/ajg.2011.1 SCOPUS: 79955601017

Machado A.M.D., Figueiredo C., Seruca R., Rasmussen L.J.,
Helicobacter pylori infection generates genetic instability in gastric cells. Biochimica et Biophysica Acta - Reviews on Cancer1806(1):58-65, 2010. [Journal: Review] [CI: 79] [IF: 9,9]
DOI: 10.1016/j.bbcan.2010.01.007 SCOPUS: 77953718630

Oliveira M.J., Costa A.M., Costa A.C., Ferreira R.M., Sampaio P., Machado J.C., Seruca R., Mareei M., Figueiredo C.,
CagA associates with c-met, E-cadherin, and p120catenin in a multiproteic complex that suppresses helicobacter pylori-induced cell-invasive phenotype. Journal of Infectious Diseases200(5):745-755, 2009. [Journal: Article] [CI: 79] [IF: 5,9]
DOI: 10.1086/604727 SCOPUS: 67649120160

Machado A.M.D., Figueiredo C., Touati E., Máximo V., Sousa S., Michel V., Carneiro F., Nielsen F.C., Seruca R., Rasmussen L.J.,
Helicobacter pylori infection induces genetic instability of nuclear and mitochondrial DNA in gastric cells. Clinical Cancer Research15(9):2995-3002, 2009. [Journal: Article] [CI: 121] [IF: 6,7]
DOI: 10.1158/1078-0432.CCR-08-2686 SCOPUS: 65649154690

Oliveira M.J., Costa A.C., Costa A.M., Henriques L., Suriano G., Atherton J.C., Machado J.C., Carneiro F., Seruca R., Mareel M., Leroy A., Figueiredo C.,
Helicobacter pylori induces gastric epithelial cell invasion in a c-Met and type IV secretion system-dependent manner. Journal of Biological Chemistry281(46):34888-34896, 2006. [Journal: Article] [CI: 86] [IF: 5,8]
DOI: 10.1074/jbc.M607067200 SCOPUS: 33845953709

Machado J.C., Figueiredo C., Canedo P., Pharoah P., Carvalho R., Nabais S., Castro Alves C., Campos M.L., Van Doorn L.J., Caldas C., Seruca R., Carneiro F., Sobrinho-Simões M.,
A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma. Gastroenterology125(2):364-371, 2003. [Journal: Article] [CI: 443] [IF: 12,7]
DOI: 10.1016/S0016-5085(03)00899-0 SCOPUS: 0042667008

Figueiredo C., Machado J.C., Pharoah P., Seruca R., Sousa S., Carvalho R., Capelinha A.F., Quint W., Caldas C., van Doorn L.J., Carneiro F., Sobrinho-Simões M.,
Helicobacter pylori and interleukin 1 genotyping: An opportunity to identify high-risk individuals for gastric carcinoma. Journal of the National Cancer Institute94(22):1680-1687, 2002. [Journal: Article] [CI: 564] [IF: 14,5]
DOI: 10.1093/jnci/94.22.1680 SCOPUS: 0037146297

Nogueira C., Figueiredo C., Carneiro F., Gomes A.T., Barreira R., Figueira P., Salgado C., Belo L., Peixoto A., Bravo J.C., Bravo L.E., Realpe J.L., Plaisier A.P., Quint W.G.V., Ruiz B., Correa P., Doorn L.J.V.,
Helicobacter pylori genotypes may determine gastric histopathology. American Journal of Pathology158(2):647-654, 2001. [Journal: Article] [CI: 172] [IF: 7,1]
DOI: 10.1016/S0002-9440(10)64006-0 SCOPUS: 0035135354

Figueiredo C., Quint W., Nouhan N., Van Den Munckhof H., Herbrink P., Scherpenisse J., De Boer W., Schneeberger P., Perez-Perez G., Blaser M.J., Van Doorn L.J.,
Assessment of helicobacter pylori vacA and cagA genotypes and host serological response. Journal of Clinical Microbiology39(4):1339-1344, 2001. [Journal: Article] [CI: 38] [IF: 4]
DOI: 10.1128/JCM.39.4.1339-1344.2001 SCOPUS: 0035060726

Figueiredo C., Quint W.G.V., Sanna R., Sablon E., Donahue J.P., Xu Q., Miller G.G., Peek R.M., Blaser M.J., Van Doorn L.J.,
Genetic organization and heterogeneity of the iceA locus of Helicobacter pylori. Gene246(1-2):59-68, 2000. [Journal: Article] [CI: 65] [IF: 2,5]
DOI: 10.1016/S0378-1119(00)00054-8 SCOPUS: 0034603794

Van Doorn L.J., Figueiredo C., Mégraud F., Pena S., Midolo P., De Magalhaes Queiroz D.M., Carneiro F., Vanderborght B., Pegado M.D.G.F., Sanna R., De Boer W., Schneeberger P.M., Correa P., Ng E.K.W., Atherton J., Blaser M.J., Quint W.G.V.,
Geographic distribution of vacA allelic types of Helicobacter pylori. Gastroenterology116(4):823-830, 1999. [Journal: Article] [CI: 385] [IF: 12,2]
DOI: 10.1016/S0016-5085(99)70065-X SCOPUS: 0033001144

Van Doorn L.J., Figueiredo C., Sanna R., Blaser M.J., Quint W.G.V.,
Distinct variants of Helicobacter pylori cagA are associated with vacA subtypes. Journal of Clinical Microbiology37(7):2306-2311, 1999. [Journal: Article] [CI: 87] [IF: 3,7]
DOI: 10.1128/jcm.37.7.2306-2311.1999 SCOPUS: 0033032564

Van Doorn L.J., Figueiredo C., Sanna R., Plaisier A., Schneeberger P., De Boer W., Quint W.,
Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology115(1):58-66, 1998. [Journal: Article] [CI: 550] [IF: 10,3]
DOI: 10.1016/S0016-5085(98)70365-8 SCOPUS: 0031750247

Van Doorn L.J., Figueiredo C., Sanna R., Pena S., Midolo P., Ng E.K.W., Atherton J.C., Blaser M.J., Quint W.G.V.,
Expanding allelic diversity of Helicobacter pylori vacA. Journal of Clinical Microbiology36(9):2597-2603, 1998. [Journal: Article] [CI: 263] [IF: 3,6]
DOI: 10.1128/jcm.36.9.2597-2603.1998 SCOPUS: 0031850322

Ongoing Projects

Circulating Microbial Signatures for Early Diagnosis of Cancer
Reference: PTDC/BTM-TEC/0367/2021
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-JAN-22 to 31-DEC-24
An artificially intelligent diagnostic assistant for gastric inflammation
Reference: HORIZON-HLTH-2022-STAYHLTH-02-01-RIA- GA 101095359
Proponent: Fundacion Incliva
Sponsor: CE - Comissão Europeia
From 01-JAN-23 to 31-DEC-26
Unveiling microbiome metabolite signatures in gastrointestinal cancers
Reference: 2022.02141.PTDC
Proponent: Instituto de Investigação e Inovação em Saúde - Universidade do Porto
Sponsor: FCT - Fundação para a Ciência e a Tecnologia
From 01-FEB-23 to 31-JAN-25
Helicobacter pylori sensitivity to clarithromycin in Fiji using genetic testing of paraffin fixed biopsy specimens
Proponent: Ipatimup
Sponsor: World Gastroenterology
From 01-JAN-21 to 31-DEC-24