Skip to main content
Erschienen in: Irish Journal of Medical Science (1971 -) 3/2022

02.06.2021 | Original Article

Expression and clinical significance of organic cation transporter family in glioblastoma multiforme

verfasst von: Qingbei Lian, Shiling Xiao, Yunda Wang, Haocong Wang, Didong Xie

Erschienen in: Irish Journal of Medical Science (1971 -) | Ausgabe 3/2022

Einloggen, um Zugang zu erhalten

Abstract

Background

Solute carrier (SLC) 22 A1, A2, and A3 are polyspecific transporters transporting organic cations like histamine, serotonin, norepinephrine, dopamine, MPP + , and toxins. The expression of SLC22A1–A3 in cancer is seldom investigated, and the function of SLC22A1–A3 in glioblastoma multiforme (GBM) is never elucidated.

Materials

In our study, we detected the expression of SLC22A1–A3 in 11 fresh GBMs and tumor-adjacent brain tissues with qPCR, and in 129 paraffin-embedded GBMs with immunohistochemistry (IHC). With chi-square test, we investigated the correlation between expression of SLC22A1–A3 and the clinicopathological factors including patients’ age, sex, tumor size, and KPS score. With Kaplan–Meier method and Cox-regression model, we estimated the prognostic significance of SLC22A1–A3 in GBM.

Results

SLC22A3 was significantly downregulated in GBMs compared with the tumor-adjacent normal tissues. With univariate survival analyses, we showed that SLC22A3, instead of SLC22A1 and A2, was an independent biomarker predicting favorable prognosis. With multivariate analyses, SLC22A3 was identified as an independent prognostic biomarker indicating the favorable outcome of GBM.

Conclusions

SLC22A3 is an independent favorable prognostic biomarker of GBM. Patients with low SLC22A3 may be more high-risk and should receive more intensive post-operational supervision and treatments.
Literatur
1.
Zurück zum Zitat Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507CrossRef Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507CrossRef
2.
Zurück zum Zitat Ostrom QT, Gittleman H, Fulop J et al (2015) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro-oncology 17 Suppl 4: iv1-iv62 Ostrom QT, Gittleman H, Fulop J et al (2015) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2008–2012. Neuro-oncology 17 Suppl 4: iv1-iv62
3.
Zurück zum Zitat Dong C, Fan W, Fang S (2020) PBK as a potential biomarker associated with prognosis of glioblastoma. J Mol Neurosci : MN 70:56–64CrossRef Dong C, Fan W, Fang S (2020) PBK as a potential biomarker associated with prognosis of glioblastoma. J Mol Neurosci : MN 70:56–64CrossRef
4.
Zurück zum Zitat Lee EQ, Muzikansky A, Drappatz J et al (2016) A randomized, placebo-controlled pilot trial of armodafinil for fatigue in patients with gliomas undergoing radiotherapy. Neuro Oncol 18:849–854CrossRef Lee EQ, Muzikansky A, Drappatz J et al (2016) A randomized, placebo-controlled pilot trial of armodafinil for fatigue in patients with gliomas undergoing radiotherapy. Neuro Oncol 18:849–854CrossRef
5.
Zurück zum Zitat Stupp R, Hegi ME, Mason WP et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466CrossRef Stupp R, Hegi ME, Mason WP et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466CrossRef
6.
Zurück zum Zitat Verhaak RG, Hoadley KA, Purdom E et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110CrossRef Verhaak RG, Hoadley KA, Purdom E et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110CrossRef
7.
Zurück zum Zitat Roth M, Obaidat A, Hagenbuch B (2012) OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br J Pharmacol 165:1260–1287CrossRef Roth M, Obaidat A, Hagenbuch B (2012) OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br J Pharmacol 165:1260–1287CrossRef
8.
Zurück zum Zitat Koepsell H, Endou H (2004) The SLC22 drug transporter family. Pflugers Arch 447:666–676CrossRef Koepsell H, Endou H (2004) The SLC22 drug transporter family. Pflugers Arch 447:666–676CrossRef
9.
Zurück zum Zitat Liu X (2019) SLC family transporters. Adv Exp Med Biol 1141:101–202CrossRef Liu X (2019) SLC family transporters. Adv Exp Med Biol 1141:101–202CrossRef
10.
Zurück zum Zitat Sweet DH (2005) Organic anion transporter (Slc22a) family members as mediators of toxicity. Toxicol Appl Pharmacol 204:198–215CrossRef Sweet DH (2005) Organic anion transporter (Slc22a) family members as mediators of toxicity. Toxicol Appl Pharmacol 204:198–215CrossRef
11.
Zurück zum Zitat Hsu CM, Lin PM, Chang JG et al (2017) Upregulated SLC22A3 has a potential for improving survival of patients with head and neck squamous cell carcinoma receiving cisplatin treatment. Oncotarget 8:74348–74358CrossRef Hsu CM, Lin PM, Chang JG et al (2017) Upregulated SLC22A3 has a potential for improving survival of patients with head and neck squamous cell carcinoma receiving cisplatin treatment. Oncotarget 8:74348–74358CrossRef
12.
Zurück zum Zitat Herraez E, Lozano E, Macias RI et al (2013) Expression of SLC22A1 variants may affect the response of hepatocellular carcinoma and cholangiocarcinoma to sorafenib. Hepatology 58:1065–1073CrossRef Herraez E, Lozano E, Macias RI et al (2013) Expression of SLC22A1 variants may affect the response of hepatocellular carcinoma and cholangiocarcinoma to sorafenib. Hepatology 58:1065–1073CrossRef
13.
Zurück zum Zitat Lautem A, Heise M, Grasel A et al (2013) Downregulation of organic cation transporter 1 (SLC22A1) is associated with tumor progression and reduced patient survival in human cholangiocellular carcinoma. Int J Oncol 42:1297–1304CrossRef Lautem A, Heise M, Grasel A et al (2013) Downregulation of organic cation transporter 1 (SLC22A1) is associated with tumor progression and reduced patient survival in human cholangiocellular carcinoma. Int J Oncol 42:1297–1304CrossRef
14.
Zurück zum Zitat Du K, Wu X, Ji X et al (2020) Early growth response 1 promoted the invasion of glioblastoma multiforme by elevating HMGB1. J Neuro Sci Du K, Wu X, Ji X et al (2020) Early growth response 1 promoted the invasion of glioblastoma multiforme by elevating HMGB1. J Neuro Sci
15.
Zurück zum Zitat Zhao B, Sun J, Du K, Liang N (2020) Sprouty 4 suppresses glioblastoma invasion by inhibiting ERK phosphorylation and ETS-1-induced matrix metalloproteinase-9. J Neuro Sci Zhao B, Sun J, Du K, Liang N (2020) Sprouty 4 suppresses glioblastoma invasion by inhibiting ERK phosphorylation and ETS-1-induced matrix metalloproteinase-9. J Neuro Sci
16.
Zurück zum Zitat Chen T, Li K, Liu Z et al (2021) WDR5 facilitates EMT and metastasis of CCA by increasing HIF-1alpha accumulation in Myc-dependent and independent pathways. Mol ther : the journal of the American Society of Gene Therapy Chen T, Li K, Liu Z et al (2021) WDR5 facilitates EMT and metastasis of CCA by increasing HIF-1alpha accumulation in Myc-dependent and independent pathways. Mol ther : the journal of the American Society of Gene Therapy 
17.
Zurück zum Zitat Kolz C, Schaeffeler E, Schwab M, Nies AT (2021) Genetic and epigenetic regulation of organic cation transporters. Handb Exp Pharmacol Kolz C, Schaeffeler E, Schwab M, Nies AT (2021) Genetic and epigenetic regulation of organic cation transporters. Handb Exp Pharmacol
18.
Zurück zum Zitat Schaeffeler E, Hellerbrand C, Nies AT et al (2011) DNA methylation is associated with downregulation of the organic cation transporter OCT1 (SLC22A1) in human hepatocellular carcinoma. Genome medicine 3:82CrossRef Schaeffeler E, Hellerbrand C, Nies AT et al (2011) DNA methylation is associated with downregulation of the organic cation transporter OCT1 (SLC22A1) in human hepatocellular carcinoma. Genome medicine 3:82CrossRef
19.
Zurück zum Zitat Tomlins SA, Mehra R, Rhodes DR et al (2007) Integrative molecular concept modeling of prostate cancer progression. Nat Genet 39:41–51CrossRef Tomlins SA, Mehra R, Rhodes DR et al (2007) Integrative molecular concept modeling of prostate cancer progression. Nat Genet 39:41–51CrossRef
20.
Zurück zum Zitat Ren A, Sun S, Li S et al (2019) Genetic variants in SLC22A3 contribute to the susceptibility to colorectal cancer. Int J Cancer 145:154–163CrossRef Ren A, Sun S, Li S et al (2019) Genetic variants in SLC22A3 contribute to the susceptibility to colorectal cancer. Int J Cancer 145:154–163CrossRef
21.
Zurück zum Zitat Heise M, Lautem A, Knapstein J et al (2012) Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance. BMC Cancer 12:109CrossRef Heise M, Lautem A, Knapstein J et al (2012) Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance. BMC Cancer 12:109CrossRef
22.
Zurück zum Zitat Cervenkova L, Vycital O, Bruha J et al (2019) Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma. Sci Rep 9:19782CrossRef Cervenkova L, Vycital O, Bruha J et al (2019) Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma. Sci Rep 9:19782CrossRef
23.
Zurück zum Zitat Mohelnikova-Duchonova B, Brynychova V, Hlavac V et al (2013) The association between the expression of solute carrier transporters and the prognosis of pancreatic cancer. Cancer Chemother Pharmacol 72:669–682CrossRef Mohelnikova-Duchonova B, Brynychova V, Hlavac V et al (2013) The association between the expression of solute carrier transporters and the prognosis of pancreatic cancer. Cancer Chemother Pharmacol 72:669–682CrossRef
24.
Zurück zum Zitat Wu X, Huang W, Ganapathy ME et al (2000) Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol 279:F449-458CrossRef Wu X, Huang W, Ganapathy ME et al (2000) Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol 279:F449-458CrossRef
25.
Zurück zum Zitat Amphoux A, Vialou V, Drescher E et al (2006) Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology 50: 941–952 Amphoux A, Vialou V, Drescher E et al (2006) Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology 50: 941–952
26.
Zurück zum Zitat Grundemann D, Schechinger B, Rappold GA, Schomig E (1998) Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat Neurosci 1:349–351CrossRef Grundemann D, Schechinger B, Rappold GA, Schomig E (1998) Molecular identification of the corticosterone-sensitive extraneuronal catecholamine transporter. Nat Neurosci 1:349–351CrossRef
27.
Zurück zum Zitat Pavlidis N, Kalef-Ezra J, Briassoulis E et al (1994) Evaluation of six tumor markers in patients with carcinoma of unknown primary. Med Pediatr Oncol 22:162–167CrossRef Pavlidis N, Kalef-Ezra J, Briassoulis E et al (1994) Evaluation of six tumor markers in patients with carcinoma of unknown primary. Med Pediatr Oncol 22:162–167CrossRef
Metadaten
Titel
Expression and clinical significance of organic cation transporter family in glioblastoma multiforme
verfasst von
Qingbei Lian
Shiling Xiao
Yunda Wang
Haocong Wang
Didong Xie
Publikationsdatum
02.06.2021
Verlag
Springer International Publishing
Erschienen in
Irish Journal of Medical Science (1971 -) / Ausgabe 3/2022
Print ISSN: 0021-1265
Elektronische ISSN: 1863-4362
DOI
https://doi.org/10.1007/s11845-021-02675-3

Weitere Artikel der Ausgabe 3/2022

Irish Journal of Medical Science (1971 -) 3/2022 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Blutdrucksenkung könnte Uterusmyome verhindern

Frauen mit unbehandelter oder neu auftretender Hypertonie haben ein deutlich erhöhtes Risiko für Uterusmyome. Eine Therapie mit Antihypertensiva geht hingegen mit einer verringerten Inzidenz der gutartigen Tumoren einher.

„Jeder Fall von plötzlichem Tod muss obduziert werden!“

17.05.2024 Plötzlicher Herztod Nachrichten

Ein signifikanter Anteil der Fälle von plötzlichem Herztod ist genetisch bedingt. Um ihre Verwandten vor diesem Schicksal zu bewahren, sollten jüngere Personen, die plötzlich unerwartet versterben, ausnahmslos einer Autopsie unterzogen werden.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Schlechtere Vorhofflimmern-Prognose bei kleinem linken Ventrikel

17.05.2024 Vorhofflimmern Nachrichten

Nicht nur ein vergrößerter, sondern auch ein kleiner linker Ventrikel ist bei Vorhofflimmern mit einer erhöhten Komplikationsrate assoziiert. Der Zusammenhang besteht nach Daten aus China unabhängig von anderen Risikofaktoren.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.