Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Medical Oncology
Published in: Medical Oncology 9/2014

01-09-2014 | Original Paper

CISD2 expression is a novel marker correlating with pelvic lymph node metastasis and prognosis in patients with early-stage cervical cancer

Authors: Luxin Liu, Meng Xia, Jing Wang, Weijing Zhang, Yanna Zhang, Mian He

Published in: Medical Oncology | Issue 9/2014

Login to get access

Abstract

The CDGSH iron sulfur domain2 (CISD2) is an evolutionarily conserved gene. It functions to control mammalian life span and regulate human breast cancer cells proliferation. However, the characteristics of CISD2 expression and its clinical/prognostic significance are unclear in human tumor. Our study aimed to investigate the expression pattern and clinicopathological significance of CISD2 in patients with early-stage cervical cancer. The mRNA and protein expression levels of CISD2 were analyzed in eight cervical cancer cell lines and eight paired cervical cancer tumors by real-time PCR and Western blotting, respectively. Immunohistochemistry was performed to examine CISD2 protein expression in paraffin-embedded tissues from 149 early-stage cervical cancer patients. Statistical analyses were used to evaluate the clinicopathological significance of CISD2 expression. CISD2 expression was significantly upregulated in cervical cancer cells at both the mRNA and protein levels. Statistical analysis showed a significant correlation of CISD2 expression with the squamous cell carcinoma antigen (P = 0.000), myometrium invasion (P = 0.003), recurrence (P = 0.012), lymphovascular space involvement (P = 0.019) and especially pelvic lymph node metastasis (PLNM; P = 0.000). Patients with higher CISD2 expression had shorter overall survival duration than patients with lower CISD2 expression. Multivariate analysis suggested that CISD2 expression might be an independent prognostic indicator for the survival of patients with early-stage cervical cancer. Our results for the first time suggested that high CISD2 expression was closely correlated with PLNM and poor prognosis in early-stage cervical cancer patients. CISD2 protein might be a novel biomarker for early-stage cervical cancer progression.
Appendix
Available only for authorised users
Literature
1.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.PubMedCrossRef
2.
Kodama J, Seki N, Masahiro S, Kusumoto T, Nakamura K, Hongo A, Hiramatsu K. Prognostic factors in stage IB–IIB cervical adenocarcinoma patients treated with radical hysterectomy and pelvic lymphadenectomy. J Surg Oncol. 2010;101(5):413–7.PubMed
3.
Noordhuis MG, Fehrmann RS, Wisman GB, Nijhuis ER, van Zanden JJ, Moerland PD, van Themaat EVL, Volders HH, Kok M, ten Hoor KA, Hollema H, de Vries EG, de Bock GH, van der Zee AG, Schuuring E. Involvement of the TGF-beta and beta-catenin pathways in pelvic lymph node metastasis in early-stage cervical cancer. Clin Cancer Res. 2011;17(6):1317–30.PubMedCrossRef
4.
Berek JS, Hacker NF. Practical gynecologic oncology. Philadelphia: Lippincott Williams & Wilkins; 2004.
5.
Conlan AR, Axelrod HL, Cohen AE, Abresch EC, Zuris J, Yee D, Nechushtai R, Jennings PA, Paddock ML. Crystal structure of Miner1: the redox-active 2Fe-2S protein causative in wolfram syndrome 2. J Mol Biol. 2009;392(1):143–53.PubMedCrossRefPubMedCentral
6.
Paddock ML, Wiley SE, Axelrod HL, Cohen AE, Roy M, Abresch EC, Capraro D, Murphy AN, Nechushtai R, Dixon JE, Jennings PA. MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc Natl Acad Sci USA. 2007;104(36):14342–7.PubMedCrossRefPubMedCentral
7.
Chen YF, Kao CH, Chen YT, Wang CH, Wu CY, Tsai CY, Liu FC, Yang CW, Wei YH, Hsu MT, Tsai SF, Tsai TF. Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes Dev. 2009;23(10):1183–94.PubMedCrossRefPubMedCentral
8.
Wu CY, Chen YF, Wang CH, Kao CH, Zhuang HW, Chen CC, Chen LK, Kirby R, Wei YH, Tsai SF, Tsai TF. A persistent level of Cisd2 extends healthy lifespan and delays aging in mice. Hum Mol Genet. 2012;21(18):3956–68.PubMedCrossRef
9.
Chen YF, Wu CY, Kirby R, Kao CH, Tsai TF. A role for the CISD2 gene in lifespan control and human disease. Ann N Y Acad Sci. 2010;1201:58–64.PubMedCrossRef
10.
Chen YF, Wu CY, Kirby R, Kao CH, Tsai TF. Cisd2 mediates mitochondrial integrity and life span in mammals. Autophagy. 2009;5(7):1043–5.PubMedCrossRef
11.
Chang NC, Nguyen M, Shore GC. BCL2-CISD2: an ER complex at the nexus of autophagy and calcium homeostasis? Autophagy. 2012;8(5):856–7.PubMedCrossRef
12.
Chang NC, Nguyen M, Germain M, Shore GC. Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1. EMBO J. 2010;29(3):606–18.PubMedCrossRefPubMedCentral
13.
Chang NC, Nguyen M, Bourdon J, Risse PA, Martin J, Danialou G, Rizzuto R, Petrof BJ, Shore GC. Bcl-2-associated autophagy regulator Naf-1 required for maintenance of skeletal muscle. Hum Mol Genet. 2012;21(10):2277–87.PubMedCrossRef
14.
Bu X, Rotter JI. Wolfram syndrome: a mitochondrial mediated disorder? Lancet. 1993;342(8871):598–600.PubMedCrossRef
15.
16.
Puca AA, Daly MJ, Brewster SJ, Matise TC, Barrett J, Shea-Drinkwater M, Kang S, Joyce E, Nicoli J, Benson E, Kunkel LM, Perls T. A genome-wide scan for linkage to human exceptional longevity identifies a locus on chromosome 4. Proc Natl Acad Sci USA. 2001;98(18):10505–8.PubMedCrossRefPubMedCentral
17.
Sohn YS, Tamir S, Song L, Michaeli D, Matouk I, Conlan AR, Harir Y, Holt SH, Shulaev V, Paddock ML, Hochberg A, Cabanchick IZ, Onuchic JN, Jennings PA, Nechushtai R, Mittler R. NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth. PNAS. 2009;110(36):14676–81.CrossRef
18.
Benedet JL, Bender H, Jones H 3rd, Ngan NY, Pecorelli S. FIGO staging classifications and clinical practice guidelines in the management of gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J Gynaecol Obstet. 2000;70(2):209–62.PubMedCrossRef
19.
Selman TJ, Mann C, Zamora J, Appleyard TL, Khan K. Diagnostic accuracy of tests for lymph node status in primary cervical cancer: a systematic review and meta-analysis. CMAJ. 2008;178(7):855–62.PubMedCrossRefPubMedCentral
20.
Esajas MD, Duk JM, De Bruijn HWA, Aalders JG, Willemse PHB, Sluiter W, Pras B, ten Hoor K, Hollema H, van der Zee AG. Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with early-stage cervical cancer. J Clin Oncol. 2001;19(19):3960–6.PubMed
21.
Pras E, Willemse PHB, Canrinus AA, De Bruijn HWA, Sluiter WJ, Ten Hoor KA, Aalders JG, Szabo BG, de Vries EG. Serum squamous cell carcinoma antigen and CYFRA 21-1 in cervical cancer treatment. Int J Rad Oncol Biol Phys. 2002;52(1):23–32.CrossRef
22.
Duk JM, Groenier KH, de Bruijn HW, Hollema H, ten Hoor KA, van der Zee AG, Aalders JG. Pretreatment serum squamous cell carcinoma antigen: a newly identified prognostic factor in early-stage cervical carcinoma. J Clin Oncol. 1996;14(1):111–8.PubMed
23.
Lin H, ChangChien CC, Huang EY, Tseng CW, Eng HL, Huang CC. The role of pretreatment squamous cell carcinoma antigen in predicting nodal metastasis in early stage cervical cancer. Acta Obstet Gynecol Scand. 2000;79(2):140–4.PubMedCrossRef
24.
Bolger BS, Dabbas M, Lopes A, Monaghan JM. Prognostic value of preoperative squamous cell carcinoma antigen level in patients surgically treated for cervical carcinoma. Gynecol Oncol. 1997;65(2):309–13.PubMedCrossRef
25.
Juang CM, Wang PH, Yen MS, Lai CR, Ng HT, Yuan CC. Application of tumor markers CEA, TPA, andSCC-Ag in patients with low-risk FIGO stage IBand IIA squamous cell carcinoma of the uterine cervix. Gynecol Oncol. 2000;6(1):103–6.CrossRef
26.
Gaarenstroom KN, Kenter GG, Bonfrer JM, Korse CM, Van de Vijver MJ, Fleuren GJ, Trimbos JB. Can initial serum cyfra 21-1, SCC antigen, and TPA levels in squamous cell cervical cancer predict lymph node metastases or prognosis? Gynecol Oncol. 2000;77(1):164–70.PubMedCrossRef
27.
van de Lande J, Davelaar EM, von Mensdorff-Pouilly S, Water TJ, Berkhof J, van Baal WM, Kenemans P, Verheijen RH. SCC-Ag, lymph node metastases and sentinel node procedure in early stage squamous cell cervical cancer. Gynecol Oncol. 2009;112(1):119–25.PubMedCrossRef
28.
29.
Tait SW, Green DR. Mitochondria and cell death: outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol. 2010;11(9):621–32.PubMedCrossRef
30.
31.
Zhang J, Yang Z, Xie L, Xu L, Xu D, Liu X. Statins, autophagy and cancer metastasis. Int J Biochem Cell Biol. 2013;45(3):745–52.PubMedCrossRef
32.
Joseph SK, Hajnóczky G. IP3 receptors in cell survival and apoptosis: Ca2+ release and beyond. Apoptosis. 2007;12(5):951–68.PubMedCrossRef
33.
Giorgi C, Baldassari F, Bononi A, Bonora M, DeMarchi E, Marchi S, Missiroli S, Patergnani S, Rimessi A, Suski JM, Wieckowski MR, Pinton P. Mitochondrial Ca2+ and apoptosis. Cell Calcium. 2012;52:36–43.PubMedCrossRefPubMedCentral
34.
Giorgi C, Wieckowski MR, Pandolfi PP, Pinton P. Mitochondria associated membranes (MAMs) as critical hubs for apoptosis. Commun Integr Biol. 2011;4(3):334–5.PubMedCrossRefPubMedCentral
35.
Marchi S, Patergnani S, Pinton P. The endoplasmic reticulum–mitochondria connection: one touch, multiple functions. Biochim Biophys Acta. 2013;1837(4):461–9.PubMedCrossRef
36.
Decuypere JP, Monaco G, Bultynck G, Missiaen L, De Smedt H, Parys JB. The IP3 receptor–mitochondria connection in apoptosis and autophagy. Biochim Biophys Acta. 2011;1813(5):1003–13.PubMedCrossRef
37.
Rong Y, Distelhorst CW. Bcl-2 protein family members: versatile regulators of calcium signaling in cell survival and apoptosis. Annu Rev Physiol. 2008;70:73–91.PubMedCrossRef
38.
Chen R, Valencia R, Zhong F, McColl KS, Roderick HL, Bootman MD, Berridge MJ, Conway SJ, Holmes AB, Mignery GA, Velez P, Distelhorst CW. Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate. J Cell Biol. 2004;166(2):193–203.PubMedCrossRefPubMedCentral
39.
Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T, Korsmeyer SJ. Bax and Bak regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science. 2003;300(5616):135–9.PubMedCrossRef
40.
Monaco G, Decrock E, Akl H, Ponsaerts R, Vervliet T, Luyten T, De Maeyer M, Missiaen L, Distelhorst CW, De Smedt H, Parys JB, Leybaert L, Bultynck G. Selective regulation of IP3-receptor-mediated Ca2 + signaling and apoptosis by the BH4 domain of Bcl-2 versus Bcl-Xl. Cell Death Differ. 2012;19(2):295–309.PubMedCrossRefPubMedCentral
41.
Cheng EH, Levine B, Boise LH, Thompson CB, Hardwick JM. Bax-independent inhibition of apoptosis by Bcl-Xl. Nature. 1996;379(6565):554–6.PubMedCrossRef
42.
Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell. 2002;2(3):183–92.PubMedCrossRef
43.
Liu L, Yu X, Guo X, Tian Z, Su M, Long Y, Huang C, Zhou F, Liu M, Wu X, Wang X. miR-143 is downregulated in cervical cancer and promotes apoptosis and inhibits tumor formation by targeting Bcl-2. Mol Med Rep. 2012;5(3):753–60.PubMed
44.
Dimitrakakis C, Kymionis G, Diakomanolis E, Papaspyrou I, Rodolakis A, Arzimanoglou I, Leandros E, Michalas S. The possible role of p53 and bcl-2 expression in cervical carcinomas and their premalignant lesions. Gynecol Oncol. 2000;77(1):129–36.PubMedCrossRef
45.
Cory S, Adams JM. The BCL2 family: regulators of the cellular life-or-death switch. Nat Rev. 2002;2(9):647–56.CrossRef
46.
Mayo MW, Baldwin AS. The transcription factor NF-κB: control of oncogenesis and cancer therapy resistance. Biochim Biophys Acta. 2000;1470(2):M55–62.PubMed
47.
Chou RH, Hsieh SC, Yu YL, Huang MH, Huang YC, Hsieh YH. Fisetin inhibits migration and invasion of human cervical cancer cells by down-regulating urokinase plasminogen activator expression through suppressing the p38 MAPK-dependent NF-κB signaling pathway. PLoS One. 2013;8(8):1–12.
48.
Yan S, Wang Y, Yang Q, Li X, Kong X, Zhang N, Yuan C, Yang N, Kong B. Low-dose radiation-induced epithelial-mesenchymal transition through NF-κB in cervical cancer cells. Int J Oncol. 2013;42(5):1801–6.PubMed
Metadata
Title
CISD2 expression is a novel marker correlating with pelvic lymph node metastasis and prognosis in patients with early-stage cervical cancer
Authors
Luxin Liu
Meng Xia
Jing Wang
Weijing Zhang
Yanna Zhang
Mian He
Publication date
01-09-2014
Publisher
Springer US
Published in
Medical Oncology / Issue 9/2014
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0183-5

Other articles of this Issue 9/2014

Medical Oncology 9/2014 Go to the issue

Original Paper

The clinical and pathological features of 133 colorectal cancer patients with brain metastasis: a multicenter retrospective analysis of the Gastrointestinal Tumors Working Committee of the Turkish Oncology Group (TOG)

Original Paper

Molecular spectrum of KRAS, BRAF, and PIK3CA gene mutation: determination of frequency, distribution pattern in Indian colorectal carcinoma

Original Paper

Serum ferritin level is prognostic of patient outcome in extranodal NK/T cell lymphoma, nasal type

Original Paper

Toxicity of concurrent chemoradiotherapy with cetuximab for locoregionally advanced nasopharyngeal carcinoma

Review Article

Cancer stem cell detection and isolation

Original Paper

The prognostic value of Cyclin B1 in pancreatic cancer
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits