Glycolytic pathway candidate markers in the prognosis of oral squamous cell carcinoma: a systematic review with meta-analysis

Molecular changes that affect mitochondrial glycolysis have been associated with the maintenance of tumor cells. Some metabolic factors have already been described as predictors of disease severity and outcomes. This systematic review was conducted to answer the question: Is the glycolytic pathway correlated with the prognosis of oral squamous cell carcinoma (OSCC)? A search strategy was developed to retrieve studies in English from PubMed, Scopus, and ISI Web of Science using keywords related to squamous cell carcinoma, survival, and glycolytic pathway, with no restriction of publication date. The search retrieved 1273 publications. After the titles and abstracts were analyzed, 27 studies met inclusion criteria. Studies were divided into groups according to two subtopics, glycolytic pathways and diagnosis, which describe the glycolytic profile of OSCC tumors. Several components of tumor energy metabolism found in this review are important predictors of survival of patients with OSCC.

Oral cancer; Survival; Prognosis; Disease-free survival; Energy metabolism

Authorship

S.E.C. de Mattos

Programa de Pós-graduação em Ciências Biológicas, Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, BrasilUniversidade Federal do Rio Grande do SulBrasilPorto Alegre, RS, BrasilPrograma de Pós-graduação em Ciências Biológicas, Fisiologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil

https://orcid.org/0000-0001-6628-8797

L.F. Diel

Faculdade de Odontologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, BrasilUniversidade Federal do Rio Grande do SulBrasilPorto Alegre, RS, BrasilFaculdade de Odontologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil

https://orcid.org/0000-0003-1526-2575

L.S. Bittencourt

Instituto Federal da Educação, Ciência e Tecnologia do Rio Grande do Sul - Porto Alegre Campus, Porto Alegre, RS, BrasilInstituto Federal da Educação, Ciência e Tecnologia do Rio Grande do Sul - Porto Alegre CampusBrasilRS, BrasilInstituto Federal da Educação, Ciência e Tecnologia do Rio Grande do Sul - Porto Alegre Campus, Porto Alegre, RS, Brasil

Secretaria de Educação do Estado do Rio Grande do Sul, Escola Técnica em Saúde, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, BrasilHospital de Clínicas de Porto AlegreBrasilPorto Alegre, RS, BrasilSecretaria de Educação do Estado do Rio Grande do Sul, Escola Técnica em Saúde, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brasil

https://orcid.org/0000-0001-9649-556X

C.E. Schnorr

Departamento de Ciências Naturales y Exactas, Universidad De La Costa, Barranquilla, Atlántico, ColombiaUniversidad De La CostaColombiaBarranquilla, Atlántico, ColombiaDepartamento de Ciências Naturales y Exactas, Universidad De La Costa, Barranquilla, Atlántico, Colombia

https://orcid.org/0000-0002-2047-2107

F.A. Gonçalves

https://orcid.org/0000-0001-8019-1684

L. Bernardi

Departamento de Ciências Morfológicas, Instituto Básico de Ciências da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, BrasilUniversidade Federal do Rio Grande do SulBrasilPorto Alegre, RS, BrasilDepartamento de Ciências Morfológicas, Instituto Básico de Ciências da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil

https://orcid.org/0000-0001-9756-4053

M.L. Lamers Correspondence: M.L. Lamers: <marcelo.lamers@ufrgs.br>

https://orcid.org/0000-0001-5296-5662

Correspondence: M.L. Lamers: <marcelo.lamers@ufrgs.br>

SCIMAGO INSTITUTIONS RANKINGS

Figures | Tables

Figures (5)
Tables (1)

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Figure 1
Study flow diagram for the literature search and selection of articles for this systematic review and meta-analysis.

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Figure 2
A, Correlation between GLUT-1 and overall survival in oral squamous cell carcinoma (OSCC) (HR=2.553, 95%CI: 1.828-3.564, P=0.000, fixed effect model). B, Correlation between positron emission tomography-computed tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) standardized uptake value-max parameter and overall survival in OSCC (HR=4.042, 95%CI: 2.573-6.348, P=0.000, fixed effect model). GLUT-1: glucose transporter-1; HR: hazard ratio. See Supplementary Table S1 for the reference numbers of the studies.

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Figure 3
Publication bias assessment for glucose transporter-1 (GLUT-1) and overall survival. A, Begg’s test (funnel plot) and B, Egger’s test (precision plot).

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Figure 4
Publication bias assessment for positron emission tomography-computed tomography standardized uptake value-max and overall survival. A, Begg’s test (funnel plot) and B, Egger’s test (precision plot).

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Figure 3
Publication bias assessment for glucose transporter-1 (GLUT-1) and overall survival. A, Begg’s test (funnel plot) and B, Egger’s test (precision plot).

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Figure 5
Flow diagram showing the impact of each marker on the energy metabolism of tumor cells evaluated by meta-analysis. The + and - symbols indicate increase and decrease of marker expression, respectively. GLUT-1: glucose transporter 1; TKTL-1: transketolase like-1; SUVmax: standard uptake value maximum; AldoC: fructose-bisphosphate aldolase C; PKM2: pyruvate kinase isoform M2; HMGCS2: mitochondrial hydroxymethylglutaryl-CoA synthase; LDHB: lactate dehydrogenase B; OSCC: oral squamous cell carcinoma; TCA: tricarboxylic acid; OAA: oxalacetate acid; MCP: mitochondrial pyruvate carrier; MCT: monocarboxylate transporter.

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Table 1
Publication bias tested by Begg’s test and Egger’s test in meta-analysis.

Figure 1 Study flow diagram for the literature search and selection of articles for this systematic review and meta-analysis.

Figure 2 A, Correlation between GLUT-1 and overall survival in oral squamous cell carcinoma (OSCC) (HR=2.553, 95%CI: 1.828-3.564, P=0.000, fixed effect model). B, Correlation between positron emission tomography-computed tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) standardized uptake value-max parameter and overall survival in OSCC (HR=4.042, 95%CI: 2.573-6.348, P=0.000, fixed effect model). GLUT-1: glucose transporter-1; HR: hazard ratio. See Supplementary Table S1 for the reference numbers of the studies.

Figure 3 Publication bias assessment for glucose transporter-1 (GLUT-1) and overall survival. A, Begg’s test (funnel plot) and B, Egger’s test (precision plot).

Figure 4 Publication bias assessment for positron emission tomography-computed tomography standardized uptake value-max and overall survival. A, Begg’s test (funnel plot) and B, Egger’s test (precision plot).

Figure 2 A, Correlation between GLUT-1 and overall survival in oral squamous cell carcinoma (OSCC) (HR=2.553, 95%CI: 1.828-3.564, P=0.000, fixed effect model). B, Correlation between positron emission tomography-computed tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose (FDG) standardized uptake value-max parameter and overall survival in OSCC (HR=4.042, 95%CI: 2.573-6.348, P=0.000, fixed effect model). GLUT-1: glucose transporter-1; HR: hazard ratio. See Supplementary Table S1 for the reference numbers of the studies.

Figure 3 Publication bias assessment for glucose transporter-1 (GLUT-1) and overall survival. A, Begg’s test (funnel plot) and B, Egger’s test (precision plot).

Figure 4 Publication bias assessment for positron emission tomography-computed tomography standardized uptake value-max and overall survival. A, Begg’s test (funnel plot) and B, Egger’s test (precision plot).

Figure 5 Flow diagram showing the impact of each marker on the energy metabolism of tumor cells evaluated by meta-analysis. The + and - symbols indicate increase and decrease of marker expression, respectively. GLUT-1: glucose transporter 1; TKTL-1: transketolase like-1; SUVmax: standard uptake value maximum; AldoC: fructose-bisphosphate aldolase C; PKM2: pyruvate kinase isoform M2; HMGCS2: mitochondrial hydroxymethylglutaryl-CoA synthase; LDHB: lactate dehydrogenase B; OSCC: oral squamous cell carcinoma; TCA: tricarboxylic acid; OAA: oxalacetate acid; MCP: mitochondrial pyruvate carrier; MCT: monocarboxylate transporter.

Table 1 Publication bias tested by Begg’s test and Egger’s test in meta-analysis.

Variables	No. of studies	Begg’s rankcorrelation P-value	Egger’s regression intercept P-value
GLUT-1 and OS	5	0.80650	0.48721
SUVMax and OS	8	0.00937	0.00085

OS: overall survival.

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Glycolytic pathway candidate markers in the prognosis of oral squamous cell carcinoma: a systematic review with meta-analysis

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[1] Correspondence: M.L. Lamers: <marcelo.lamers@ufrgs.br>