PAI‐1, CAIX, and VEGFA expressions as prognosis markers in oral squamous cell carcinoma

Peterle, Gabriela Tonini; Maia, L.L.; Trivilin, Leonardo Oliveira; Oliveira, Mayara Mota de; Santos, Joaquim Gasparini dos; Mendes, Suzanny Oliveira; Stur, Elaine; Agostini, Lidiane Pignaton; Rocha, Lucio Agostinho; Moysés, Raquel Ajub; Cury, Patrí­cia Maluf; Nunes, Fábio Daumas; Louro, Iúri Drumond; Santos, Marcelo dos; Silva, Adriana Madeira Álvares da

doi:10.1111/jop.12721

Cited by 31 publications

(31 citation statements)

References 26 publications

(59 reference statements)

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“…This was confirmed by Li and coworkers, suggesting its use as a prognostic biomarker for this disease [ 61 , 62 , 63 ]. Thus, CA IX was established as an additive prognostic marker [ 45 , 64 ]. In addition, a role of CA IX as a pH sensor was established, and the first therapeutic options by the selective inhibition of carbonic anhydrases, leading to a reversion of the multidrug resistance in tumor cells, were reported [ 65 ].…”

Section: Hif-1α Stabilization Under Normoxia Its Role In Glutaminmentioning

confidence: 99%

Current Understanding of the HIF-1-Dependent Metabolism in Oral Squamous Cell Carcinoma

Eckert

Kappler

Große

et al. 2020

IJMS

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Oral squamous cell carcinoma (OSCC) is the 10th most frequent human malignancy and is thus a global burden. Despite some progress in diagnosis and therapy, patients’ overall survival rate, between 40 and 55%, has stagnated over the last four decades. Since the tumor node metastasis (TNM) system is not precise enough to predict the disease outcome, additive factors for diagnosis, prognosis, prediction and therapy resistance are urgently needed for OSCC. One promising candidate is the hypoxia inducible factor-1 (HIF-1), which functions as an early regulator of tumor aggressiveness and is a key promoter of energy adaptation. Other parameters comprise the composition of the tumor microenvironment, which determines the availability of nutrients and oxygen. In our opinion, these general processes are linked in the pathogenesis of OSCC. Based on this assumption, the review will summarize the major features of the HIF system-induced activities, its target proteins and related pathways of nutrient utilization and metabolism that are essential for the initiation, progression and therapeutic stratification of OSCC.

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Section: Hif-1α Stabilization Under Normoxia Its Role In Glutaminmentioning

confidence: 99%

Current Understanding of the HIF-1-Dependent Metabolism in Oral Squamous Cell Carcinoma

Eckert

Kappler

Große

et al. 2020

IJMS

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“…Out of the 1741 publications which were initially retrieved, 18 studies met our inclusion criteria and were included in the meta-analysis, as depicted in Figure 1. The studies reported on a total of 1616 OSCC-affected patients [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] .…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

“…The data was collected in a period spanning from 1987 to 2015 [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] while the year of publication ranged from 2008 to 2019. The anatomic location of the tumours was mainly divided into exclusively tongue 27,28,30,31,37,39,42 , or mixed subsite tumours 29,[32][33][34][35][36]38,40,41 .…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

“…The studies were carried out in Asia, Europe, and America. Half of the studies were carried out in Asia (specifically in China 38 , Japan 27,33 , and South Korea [28][29][30]32,35,37 ) and the other half in Brazil 39,43 , Canada 34 , Germany 31,44 , Portugal 40 , Spain 36,40,42 , and the US 41 . The retrieved data are summarised in Table 1.…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

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Prognostic value of CAIX expression in oral squamous cell carcinoma: a systematic review and meta-analysis

Lorenzo-Pouso

Torreira

Pérez‐Sayáns

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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Carbonic anhydrase IX (CAIX) is a hypoxia-related protein considered as a predictor for oral squamous cell carcinoma (OSCC) biological behaviour. Nevertheless, this prognostic value is still yet to be validated. We aim to quantify prognostic significance of CAIX overexpression in OSCC by meta-analysis. We performed searches in MEDLINE, EMBASE, SCOPUS, WOS, WHO'S databases, CPCI, and OATD from inception to August 2019. Overall survival (OS), disease-free survival (DFS), locoregional control (LC), and disease-specific survival (DSS) were considered as outcomes of interest. Overall 18 studies were included. CAIX overexpression was associated with worse OS (hazard ratio [HR] ¼ 1.45 95% confidence interval [CI] 1.17-1.80) and DFS (HR ¼ 1.98 95% CI 1.18-3.32). To the contrary, it was neither associated with LC (HR ¼ 1.01 95% CI 0.50-2.02) nor with DSS (HR ¼ 1.35 95% CI 0.78-2.33). Heterogeneity was negligible in all analyses except for DSS. Small studies effect was not significant for OS and DFS. This study shows that immunohistochemical CAIX assessment is a useful OSCC prognostic biomarker.

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“…Yang et al found CA9 mRNA levels as prognostically relevant using datasets from The Cancer Genome Atlas (TCGA) of patients with oral cancer [35]. Peterle et al [37] and Brockton et al [32] described the CAIX protein level to be prognostically relevant to OSCC. Lin et al found a worse outcome of OSCC patients when lipocalin 2 (LCN2) was weak but CAIX was strongly expressed [33].…”

Section: Introductionmentioning

confidence: 99%

Investigation of the Prognostic Role of Carbonic Anhydrase 9 (CAIX) of the Cellular mRNA/Protein Level or Soluble CAIX Protein in Patients with Oral Squamous Cell Carcinoma

Eckert

Horter

Bethmann

et al. 2019

IJMS

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Carbonic anhydrase 9 (CAIX) is an important protein that stabilizes the extracellular pH value and is transcriptionally regulated by hypoxia-inducible factor 1 (HIF1), but more stable than HIF1α. Here we show a comparative study that examines the prognostic value of CA9 mRNA, CAIX protein of tumor cells and secreted CAIX protein for oral squamous cell carcinoma (OSCC) patients. Tumor samples from 72 OSCC patients and 24 samples of normal tissue were analyzed for CA9 mRNA levels. A total of 158 OSCC samples were stained for CAIX by immunohistochemistry and 89 blood serum samples were analyzed by ELISA for soluble CAIX protein content. Survival analyses were performed by Kaplan–Meier and Cox’s regression analysis to estimate the prognostic effect of CA9/CAIX in OSCC patients. The CA9 mRNA and CAIX protein levels of tumor cells correlated with each other, but not with those of the secreted CAIX protein level of the blood of patients. ROC curves showed a significant (p < 0.001) higher mRNA-level of CA9 in OSCC samples than in adjacent normal tissue. Cox’s regression analysis revealed an increased risk (i) of death for patients with a high CA9 mRNA level (RR = 2.2; p = 0.02), (ii) of locoregional recurrence (RR = 3.2; p = 0.036) at higher CA9 mRNA levels and (iii) of death at high CAIX protein level in their tumors (RR = 1.7; p = 0.066) and especially for patients with advanced T4-tumors (RR = 2.0; p = 0.04). However, the secreted CAIX protein level was only as a trend associated with prognosis in OSCC (RR = 2.2; p = 0.066). CA9/CAIX is an independent prognostic factor for OSCC patients and therefore a potential therapeutic target.

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PAI‐1, CAIX, and VEGFA expressions as prognosis markers in oral squamous cell carcinoma

Abstract: Our results suggest a potential role for these expressions profiles as tumor prognostic markers in OSCC patients.

Cited by 31 publications

References 26 publications

Current Understanding of the HIF-1-Dependent Metabolism in Oral Squamous Cell Carcinoma

Current Understanding of the HIF-1-Dependent Metabolism in Oral Squamous Cell Carcinoma

Prognostic value of CAIX expression in oral squamous cell carcinoma: a systematic review and meta-analysis

Investigation of the Prognostic Role of Carbonic Anhydrase 9 (CAIX) of the Cellular mRNA/Protein Level or Soluble CAIX Protein in Patients with Oral Squamous Cell Carcinoma

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