nach oben

Tumor Biology

Erschienen in:

07.11.2015 | Original Article

Down-regulation of succinate dehydrogenase subunit B and up-regulation of pyruvate dehydrogenase kinase 1 predicts poor prognosis in recurrent nasopharyngeal carcinoma

verfasst von: ZhiJian Dai, Shenhua Pan, Congxi Chen, Longhe Cao, Xianhui Li, Xiaofeng Chen, Xiaoqing Su, Sen Lin

Erschienen in: Tumor Biology | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Abstract

Succinate dehydrogenase subunit B (SDHB) and pyruvate dehydrogenase kinase 1 (PDK1) play key roles in the regulation of growth and survival of various cancers. This study aimed to investigate expression of SDHB and PDK1 in recurrent nasopharyngeal carcinoma (rNPC) tissues and analyzed the association of SDHB and PDK1 expression with the clinical significance and potential prognostic implication of rNPC. Immunohistochemistry was performed to determine the expression of SDHB and PDK1 in tissues in primary NPC (pNPC) and rNPC patients. Our results revealed that expression of SDHB in rNPC was significantly lower than that in pNPC, while the expression of PDK1 was higher compared to pNPC. The expression levels of SDHB and PDK1 were associated with T stage, N stage, clinical stage, and metastasis of rNPC. Survival analysis showed that patients with low SDHB expression had a significantly shorter overall survival time than those with high SDHB expression. Patients with high PDK1 expression had a shorter survival time than patients with low PDK1 expression. Multivariate analysis showed that the expression of SDHB and PDK1 was an independent predictor for the survival of patients with rNPC. Our results demonstrated that down-regulation of SDHB and up-regulation of PDK1 may be novel biomarkers for predicting advanced tumor progression and unfavorable prognosis in rNPC patients.

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed

Pignon JP, Bourhis J, Domenge C, Designe L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. Mach-nc collaborative group. Meta-analysis of chemotherapy on head and neck cancer. Lancet. 2000;355:949–55.CrossRefPubMed

Chan AT, Teo PM, Ngan RK, Leung TW, Lau WH, Zee B, et al. Concurrent chemotherapy-radiotherapy compared with radiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: progression-free survival analysis of a phase III randomized trial. J Clin Oncol. 2002;20:2038–44.CrossRefPubMed

Lin JC, Jan JS, Hsu CY, Liang WM, Jiang RS, Wang WY. Phase III study of concurrent chemoradiotherapy versus radiotherapy alone for advanced nasopharyngeal carcinoma: positive effect on overall and progression-free survival. J Clin Oncol. 2003;21:631–7.CrossRefPubMed

Erkal HS, Serin M, Cakmak A. Nasopharyngeal carcinomas: analysis of patient, tumor and treatment characteristics determining outcome. Radiother Oncol. 2001;61:247–56.CrossRefPubMed

Ho FC, Tham IW, Earnest A, Lee KM, Lu JJ. Patterns of regional lymph node metastasis of nasopharyngeal carcinoma: a meta-analysis of clinical evidence. BMC Cancer. 2012;12:98.CrossRefPubMedPubMedCentral

Pawlu C, Bausch B, Neumann HP. Mutations of the SDHB and SDHD genes. Familial Cancer. 2005;4:49–54.CrossRefPubMed

Blank A, Schmitt AM, Korpershoek E, van Nederveen F, Rudolph T, Weber N, et al. SDHB loss predicts malignancy in pheochromocytomas/sympathetic paragangliomas, but not through hypoxia signalling. Endocr Relat Cancer. 2010;17:919–28.CrossRefPubMed

Shimizu T, Inoue K, Hachiya H, Shibuya N, Shimoda M, Kubota K. Frequent alteration of the protein synthesis of enzymes for glucose metabolism in hepatocellular carcinomas. J Gastroenterol. 2014;49:1324–32.CrossRefPubMed

10.

Cao Z, Song JH, Kang YW, Yoon JH, Nam SW, Lee JY, et al. Analysis of succinate dehydrogenase subunit B gene alterations in gastric cancers. Pathol Int. 2010;60:559–65.CrossRefPubMed

11.

Zhang D, Wang W, Xiang B, Li N, Huang S, Zhou W, et al. Reduced succinate dehydrogenase B expression is associated with growth and de-differentiation of colorectal cancer cells. Tumour Biol. 2013;34:2337–47.CrossRefPubMed

12.

Gill AJ, Pachter NS, Chou A, Young B, Clarkson A, Tucker KM, et al. Renal tumors associated with germline SDHB mutation show distinctive morphology. Am J Surg Pathol. 2011;35:1578–85.CrossRefPubMed

13.

Fleming S, Mayer NJ, Vlatkovic LJ, McLean J, McConachie M, Baty D. Signalling pathways in succinate dehydrogenase B-associated renal carcinoma. Histopathology. 2014;64:477–83.CrossRefPubMed

14.

Montani M, Schmitt AM, Schmid S, Locher T, Saremaslani P, Heitz PU, et al. No mutations but an increased frequency of SDHx polymorphisms in patients with sporadic and familial medullary thyroid carcinoma. Endocr Relat Cancer. 2005;12:1011–6.CrossRefPubMed

15.

Miettinen M, Sarlomo-Rikala M, McCue P, Czapiewski P, Langfort R, Waloszczyk P, et al. Mapping of succinate dehydrogenase losses in 2258 epithelial neoplasms. Appl Immunohistochem Mol Morphol. 2014;22:31–6.CrossRefPubMed

16.

Ahmed N, Riley C, Quinn MA. An immunohistochemical perspective of PPAR beta and one of its putative targets PDK1 in normal ovaries, benign and malignant ovarian tumours. Br J Cancer. 2008;98:1415–24.CrossRefPubMedPubMedCentral

17.

Yu J, Chen KS, Li YN, Yang J, Zhao L. Silencing of PDK1 gene expression by RNA interference suppresses growth of esophageal cancer. Asian Pac J Cancer Prev. 2012;13:4147–51.CrossRefPubMed

18.

Liu Y, Wang J, Wu M, Wan W, Sun R, Yang D, et al. Down-regulation of 3-phosphoinositide-dependent protein kinase-1 levels inhibits migration and experimental metastasis of human breast cancer cells. Mol Cancer Res. 2009;7:944–54.CrossRefPubMed

19.

Galgano MT, Conaway M, Spencer AM, Paschal BM, Frierson Jr HF. PRK1 distribution in normal tissues and carcinomas: overexpression and activation in ovarian serous carcinoma. Human Pathol. 2009;40:1434–40.CrossRef

20.

Han L, Zhang G, Zhang N, Li H, Liu Y, Fu A, et al. Prognostic potential of microRNA-138 and its target mRNA PDK1 in sera for patients with non-small cell lung cancer. Med Oncol. 2014;31:129.CrossRefPubMed

21.

Tsukamoto Y, Nakada C, Noguchi T, Tanigawa M, Nguyen LT, Uchida T, et al. MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3zeta. Cancer Res. 2010;70:2339–49.CrossRefPubMed

22.

Hur H, Xuan Y, Kim YB, Lee G, Shim W, Yun J, et al. Expression of pyruvate dehydrogenase kinase-1 in gastric cancer as a potential therapeutic target. Int J Oncol. 2013;42:44–54.PubMed

23.

Cen L, Hsieh FC, Lin HJ, Chen CS, Qualman SJ, Lin J. PDK-1/AKT pathway as a novel therapeutic target in rhabdomyosarcoma cells using OSU-03012 compound. Br J Cancer. 2007;97:785–91.CrossRefPubMedPubMedCentral

24.

Lin S, Huang ZX, Li WF, Zhang CH, Fang XB, Liao ZS. Function and chromosome location of differentially expressed genes in primary nasopharyngeal carcinoma. Chinese Archives of Otolaryngology-Head and Neck Surgery. 2010;17:455–7.

25.

Huang ZX, Li WF, Lin S, Huang Y, Du JM, Tan YX, et al. Identification of differentially expressed genes in recurrent nasopharyngeal carcinoma and analysis of their chromosomal location. Chinese Journal of Otorhinolaryngology Head and Neck Surgery. 2010;45:47–51.PubMed

26.

Guzy RD, Sharma B, Bell E, Chandel NS, Schumacker PT. Loss of the SdhB, but not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis. Mol Cell Biol. 2008;28:718–31.CrossRefPubMed

27.

Lendvai N, Pawlosky R, Bullova P, Eisenhofer G, Patocs A, Veech RL, et al. Succinate-to-fumarate ratio as a new metabolic marker to detect the presence of SDHB/D-related paraganglioma: initial experimental and ex vivo findings. Endocrinology. 2014;155:27–32.CrossRefPubMed

28.

Doyle LA, Nelson D, Heinrich MC, Corless CL, Hornick JL. Loss of succinate dehydrogenase subunit B (SDHB) expression is limited to a distinctive subset of gastric wild-type gastrointestinal stromal tumours: a comprehensive genotype-phenotype correlation study. Histopathology. 2012;61:801–9.CrossRefPubMed

29.

Li Y, Yang KJ, Park J. Multiple implications of 3-phosphoinositide-dependent protein kinase 1 in human cancer. World J Biol Chem. 2010;1:239–47.CrossRefPubMedPubMedCentral

30.

Bayascas JR, Leslie NR, Parsons R, Fleming S, Alessi DR. Hypomorphic mutation of PDK1 suppresses tumorigenesis in PTEN (+/−) mice. Curr Biol. 2005;15:1839–46.CrossRefPubMed

31.

Li X, Lin R, Li J. Epigenetic silencing of microRNA-375 regulates PDK1 expression in esophageal cancer. Dig Dis Sci. 2011;56:2849–56.CrossRefPubMed

32.

Tatsumi-Tamori A, Yoshizaki T, Miwa T, Furukawa M. Clinical evaluation of staging system for nasopharyngeal carcinoma: comparison of fourth and fifth editions of UICC TNM classification. Ann Otol Rhino Laryngol. 2000;109:1125–9.CrossRef

33.

Patel SG, Shah JP. TNM staging of cancers of the head and neck: striving for uniformity among diversity. CA Cancer J Clin. 2005;55:242–58.

Titel: Down-regulation of succinate dehydrogenase subunit B and up-regulation of pyruvate dehydrogenase kinase 1 predicts poor prognosis in recurrent nasopharyngeal carcinoma
verfasst von: ZhiJian Dai
Shenhua Pan
Congxi Chen
Longhe Cao
Xianhui Li
Xiaofeng Chen
Xiaoqing Su
Sen Lin
Publikationsdatum: 07.11.2015
Verlag: Springer Netherlands
Erschienen in: Tumor Biology / Ausgabe 4/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-4107-6

Neu im Fachgebiet Onkologie

24.04.2024 | DGIM 2024 | Nachrichten

Springer Medizin

Down-regulation of succinate dehydrogenase subunit B and up-regulation of pyruvate dehydrogenase kinase 1 predicts poor prognosis in recurrent nasopharyngeal carcinoma

Abstract

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2016

Knockdown of miR-221 promotes the cisplatin-inducing apoptosis by targeting the BIM-Bax/Bak axis in breast cancer

Deregulation of miR-1, miR486, and let-7a in cytogenetically normal acute myeloid leukemia: association with NPM1 and FLT3 mutation and clinical characteristics

Comparison of five models for end-stage liver disease in predicting the survival rate of patients with advanced hepatocellular carcinoma

miR-449a enhances radiosensitivity through modulating pRb/E2F1 in prostate cancer cells

Coexpression of CXCR4 and MMP9 predicts lung metastasis and poor prognosis in resected osteosarcoma

Cross-reacting material 197 reverses the resistance to paclitaxel in paclitaxel-resistant human ovarian cancer

Neu im Fachgebiet Onkologie

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Krebspatienten impfen: Was? Wen? Und wann nicht?

Müde im Alter? Auch an die Nebenniere denken

Update Onkologie