Skip to main content
Top
Published in: Journal of Experimental & Clinical Cancer Research 1/2012

Open Access 01-12-2012 | Research

Alpha B-crystallin is a new prognostic marker for laryngeal squamous cell carcinoma

Authors: Yuan Mao, Da-Wei Zhang, Hong Lin, Lin Xiong, Ying Liu, Qing-Dong Li, Jun Ma, Qing Cao, Ren-Jie Chen, Jin Zhu, Zhen-Qing Feng

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2012

Login to get access

Abstract

Background

Alpha B-crystallin (αB-crystallin) has been suggested to play an important role in the development of solid tumors. However, the association between αB-crystallin expression and clinicopathological characteristics of human laryngeal carcinoma is not well defined. This study aimed to examine the expression of αB-crystallin in human laryngeal squamous cell carcinoma (LSCC) and investigate the relationship between its expression and the prognosis of LSCC.

Methods

Real-time polymerase chain reaction (six LSCC samples, six tumor-adjacent normal samples) and immunohistochemistry by tissue microarrays (109 LSCC samples and 28 tumor-adjacent normal samples) were performed to characterize expression of the αB-crystallin gene in LSCC. Kaplan-Meier survival and Cox regression analyses were carried out to evaluate the prognosis of LSCC.

Results

Real-time polymerase chain reaction and immunohistochemistry analysis showed that the expression of αB-crystallin in LSCC was significantly higher than that in tumor-adjacent normal tissues. Moreover, the expression level of αB-crystallin protein in LSCC was significantly related to alcohol consumption (P = 0.022), tumor differentiation (P = 0.007), pTNM stage (P = 0.041) and 5 years’ survival (P =0.030). COX multi-factor analysis showed that αB-crystallin (P = 0.013), as well as pTNM stage (P =0.027) and lymphatic metastasis (P = 0.015) were independent prognosis factors for LSCC.

Conclusions

The data suggest that αB-crystallin expression is correlated with malignant phenotypes of LSCC and it may serve as a novel prognostic factor for LSCC.
Appendix
Available only for authorised users
Literature
1.
go back to reference Wu H, Xu H, Zhang S, Wang X, Zhu H, Zhang H, Zhu J, Huang J: Potential therapeutic target and independent prognostic marker of TROP2 in laryngeal squamous cell carcinoma. Head Neck. 2012, doi:10.1002/hed.23138. Wu H, Xu H, Zhang S, Wang X, Zhu H, Zhang H, Zhu J, Huang J: Potential therapeutic target and independent prognostic marker of TROP2 in laryngeal squamous cell carcinoma. Head Neck. 2012, doi:10.1002/hed.23138.
2.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 2009, 59 (4): 225-249. 10.3322/caac.20006.CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 2009, 59 (4): 225-249. 10.3322/caac.20006.CrossRefPubMed
3.
go back to reference Hoffman HT, Porter K, Karnell LH, Cooper JS, Weber RS, Langer CJ, Ang KK, Gay G, Stewart A, Robinson RA: Laryngeal cancer in the United States: changes in demographics, patterns of care, and survival. Laryngoscope. 2006, 116 (9 Pt 2 Suppl 111): 1-13.CrossRefPubMed Hoffman HT, Porter K, Karnell LH, Cooper JS, Weber RS, Langer CJ, Ang KK, Gay G, Stewart A, Robinson RA: Laryngeal cancer in the United States: changes in demographics, patterns of care, and survival. Laryngoscope. 2006, 116 (9 Pt 2 Suppl 111): 1-13.CrossRefPubMed
4.
go back to reference Boyle P, Ferlay J: Cancer incidence and mortality in Europe. Ann Oncol. 2005, 16 (3): 481-488. 10.1093/annonc/mdi098.CrossRefPubMed Boyle P, Ferlay J: Cancer incidence and mortality in Europe. Ann Oncol. 2005, 16 (3): 481-488. 10.1093/annonc/mdi098.CrossRefPubMed
5.
go back to reference Chin D, Boyle GM, Williams RM, Ferguson K, Pandeya N, Pedley J, Campbell CM, Theile DR, Parsons PG, Coman WB: Alpha B-crystallin, a new independent marker for poor prognosis in head and neck cancer. Laryngoscope. 2005, 115 (7): 1239-1242. 10.1097/01.MLG.0000164715.86240.55.CrossRefPubMed Chin D, Boyle GM, Williams RM, Ferguson K, Pandeya N, Pedley J, Campbell CM, Theile DR, Parsons PG, Coman WB: Alpha B-crystallin, a new independent marker for poor prognosis in head and neck cancer. Laryngoscope. 2005, 115 (7): 1239-1242. 10.1097/01.MLG.0000164715.86240.55.CrossRefPubMed
6.
go back to reference Moyano JV, Evans JR, Chen F, Lu M, Werner ME, Yehiely F, Diaz LK, Turbin D, Karaca G, Wiley E, Nielsen TO, Perou CM, Cryns VL: AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer. J Clin Invest. 2006, 116 (1): 261-270.PubMedCentralCrossRefPubMed Moyano JV, Evans JR, Chen F, Lu M, Werner ME, Yehiely F, Diaz LK, Turbin D, Karaca G, Wiley E, Nielsen TO, Perou CM, Cryns VL: AlphaB-crystallin is a novel oncoprotein that predicts poor clinical outcome in breast cancer. J Clin Invest. 2006, 116 (1): 261-270.PubMedCentralCrossRefPubMed
7.
go back to reference Kamradt MC, Lu M, Werner ME, Kwan T, Chen F, Strohecker A, Oshita S, Wilkinson JC, Yu C, Oliver PG, Duckett CS, Buchsbaum DJ, LoBuglio AF, Jordan VC, Cryns VL: The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3. J Biol Chem. 2005, 280 (12): 11059-11066. 10.1074/jbc.M413382200.CrossRefPubMed Kamradt MC, Lu M, Werner ME, Kwan T, Chen F, Strohecker A, Oshita S, Wilkinson JC, Yu C, Oliver PG, Duckett CS, Buchsbaum DJ, LoBuglio AF, Jordan VC, Cryns VL: The small heat shock protein alpha B-crystallin is a novel inhibitor of TRAIL-induced apoptosis that suppresses the activation of caspase-3. J Biol Chem. 2005, 280 (12): 11059-11066. 10.1074/jbc.M413382200.CrossRefPubMed
8.
go back to reference Adhikari AS, Singh BN, Rao KS, Rao CM: αB-crystallin, a small heat shock protein, modulates NF-κB activity in a phosphorylation-dependent manner and protects muscle myoblasts from TNF-α induced cytotoxicity. Biochim Biophys Acta. 2011, 1813 (8): 1532-1542. 10.1016/j.bbamcr.2011.04.009.CrossRefPubMed Adhikari AS, Singh BN, Rao KS, Rao CM: αB-crystallin, a small heat shock protein, modulates NF-κB activity in a phosphorylation-dependent manner and protects muscle myoblasts from TNF-α induced cytotoxicity. Biochim Biophys Acta. 2011, 1813 (8): 1532-1542. 10.1016/j.bbamcr.2011.04.009.CrossRefPubMed
9.
go back to reference Mao YW, Liu JP, Xiang H, Li DW: Human alphaA- and alphaBcrystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis. Cell Death Differ. 2004, 11 (5): 512-526. 10.1038/sj.cdd.4401384.CrossRefPubMed Mao YW, Liu JP, Xiang H, Li DW: Human alphaA- and alphaBcrystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis. Cell Death Differ. 2004, 11 (5): 512-526. 10.1038/sj.cdd.4401384.CrossRefPubMed
10.
go back to reference Chan SK, Lui PC, Tan PH, Yamaguchi R, Moriya T, Yu AM, Shao MM, Hliang T, Wong SI, Tse GM: Increased alpha-B-crystallin expression in mammary metaplastic carcinomas. Histopathology. 2011, 59 (2): 247-255.CrossRefPubMed Chan SK, Lui PC, Tan PH, Yamaguchi R, Moriya T, Yu AM, Shao MM, Hliang T, Wong SI, Tse GM: Increased alpha-B-crystallin expression in mammary metaplastic carcinomas. Histopathology. 2011, 59 (2): 247-255.CrossRefPubMed
11.
go back to reference Tang Q, Liu YF, Zhu XJ, Li YH, Zhu J, Zhang JP, Feng ZQ, Guan XH: Expression and prognostic significance of the αB-crystallin gene in human hepatocellular carcinoma. Hum Pathol. 2009, 40 (3): 300-305. 10.1016/j.humpath.2008.09.002.CrossRefPubMed Tang Q, Liu YF, Zhu XJ, Li YH, Zhu J, Zhang JP, Feng ZQ, Guan XH: Expression and prognostic significance of the αB-crystallin gene in human hepatocellular carcinoma. Hum Pathol. 2009, 40 (3): 300-305. 10.1016/j.humpath.2008.09.002.CrossRefPubMed
12.
go back to reference Stegh AH, Kesari S, Mahoney JE, Jenq HT, Forloney KL, Protopopov A, Louis DN, Chin L, DePinho RA: Bcl2L12-mediated inhibition of effector caspase-3 and caspase-7 via distinct mechanisms in glioblastoma. Proc Natl Acad Sci USA. 2008, 105 (31): 10703-10708. 10.1073/pnas.0712034105.PubMedCentralCrossRefPubMed Stegh AH, Kesari S, Mahoney JE, Jenq HT, Forloney KL, Protopopov A, Louis DN, Chin L, DePinho RA: Bcl2L12-mediated inhibition of effector caspase-3 and caspase-7 via distinct mechanisms in glioblastoma. Proc Natl Acad Sci USA. 2008, 105 (31): 10703-10708. 10.1073/pnas.0712034105.PubMedCentralCrossRefPubMed
13.
go back to reference Dimberg A, Rylova S, Dieterich LC, Olsson AK, Schiller P, Wikner C, Bohman S, Botling J, Lukinius A, Wawrousek EF, Claesson-Welsh L: alphaB-crystallin promotes tumor angiogenesis by increasing vascular survival during tube morphogenesis. Blood. 2008, 111 (4): 2015-2023. 10.1182/blood-2007-04-087841.CrossRefPubMed Dimberg A, Rylova S, Dieterich LC, Olsson AK, Schiller P, Wikner C, Bohman S, Botling J, Lukinius A, Wawrousek EF, Claesson-Welsh L: alphaB-crystallin promotes tumor angiogenesis by increasing vascular survival during tube morphogenesis. Blood. 2008, 111 (4): 2015-2023. 10.1182/blood-2007-04-087841.CrossRefPubMed
14.
go back to reference Kase S, He S, Sonoda S, Kitamura M, Spee C, Wawrousek E, Ryan SJ, Kannan R, Hinton DR: alphaB-crystallin regulation of angiogenesis by modulation of VEGF. Blood. 2010, 115 (16): 3398-3406. 10.1182/blood-2009-01-197095.PubMedCentralCrossRefPubMed Kase S, He S, Sonoda S, Kitamura M, Spee C, Wawrousek E, Ryan SJ, Kannan R, Hinton DR: alphaB-crystallin regulation of angiogenesis by modulation of VEGF. Blood. 2010, 115 (16): 3398-3406. 10.1182/blood-2009-01-197095.PubMedCentralCrossRefPubMed
15.
go back to reference Thompson L: World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Ear Nose Throat J. 2006, 85 (2): 74-PubMed Thompson L: World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Ear Nose Throat J. 2006, 85 (2): 74-PubMed
16.
go back to reference Friedrich M, Villena-Heinsen C, Reitnauer K, Schmidt W, Tilgen W, Reichrath J: Malignancies of the uterine corpus and immunoreactivity score of the DNA “mismatch-repair”enzyme human Mut-S-homologon-2. J Histochem Cytochem. 1999, 47 (1): 113-118. 10.1177/002215549904700112.CrossRefPubMed Friedrich M, Villena-Heinsen C, Reitnauer K, Schmidt W, Tilgen W, Reichrath J: Malignancies of the uterine corpus and immunoreactivity score of the DNA “mismatch-repair”enzyme human Mut-S-homologon-2. J Histochem Cytochem. 1999, 47 (1): 113-118. 10.1177/002215549904700112.CrossRefPubMed
17.
go back to reference Mao Y, Zhang DW, Wen J, Cao Q, Chen RJ, Zhu J, Feng ZQ: A novel LMP1 antibody synergizes with Mitomycin C to inhibit Nasopharyngeal Carcinoma growth in vivo through inducing apoptosis and downregulating vascular endothelial growth factor. Int J Mol Sci. 2012, 13 (2): 2208-2218. 10.3390/ijms13022208.PubMedCentralCrossRefPubMed Mao Y, Zhang DW, Wen J, Cao Q, Chen RJ, Zhu J, Feng ZQ: A novel LMP1 antibody synergizes with Mitomycin C to inhibit Nasopharyngeal Carcinoma growth in vivo through inducing apoptosis and downregulating vascular endothelial growth factor. Int J Mol Sci. 2012, 13 (2): 2208-2218. 10.3390/ijms13022208.PubMedCentralCrossRefPubMed
18.
go back to reference Luo XM, Zhou SH, Fan J: Glucose transporter-1 as a new therapeutic target in laryngeal carcinoma. J Int Med Res. 2010, 38 (6): 1885-1892.CrossRefPubMed Luo XM, Zhou SH, Fan J: Glucose transporter-1 as a new therapeutic target in laryngeal carcinoma. J Int Med Res. 2010, 38 (6): 1885-1892.CrossRefPubMed
19.
go back to reference Chen J, Yang B, Zhang S, Ling Y, Ye J, Jia Z, Cao J: Antitumor potential of SLPI promoter controlled recombinant caspase-3 expression in laryngeal carcinoma. Cancer Gene Ther. 2012, 19 (5): 328-335. 10.1038/cgt.2012.5.CrossRefPubMed Chen J, Yang B, Zhang S, Ling Y, Ye J, Jia Z, Cao J: Antitumor potential of SLPI promoter controlled recombinant caspase-3 expression in laryngeal carcinoma. Cancer Gene Ther. 2012, 19 (5): 328-335. 10.1038/cgt.2012.5.CrossRefPubMed
20.
go back to reference Liang W, Wang XF: In vitro induction of specific anti-tumoral immunity against laryngeal carcinoma by using human interleukin-12 gene-transfected dendritic cells. Chin Med J (Engl). 2011, 124 (9): 1357-1361. Liang W, Wang XF: In vitro induction of specific anti-tumoral immunity against laryngeal carcinoma by using human interleukin-12 gene-transfected dendritic cells. Chin Med J (Engl). 2011, 124 (9): 1357-1361.
21.
go back to reference de Souza DL B, Jerez Roig J, Bernal MM: Laryngeal cancer survival in Zaragoza (Spain): a population-based study. Clin Transl Oncol. 2012, 14 (3): 221-224. 10.1007/s12094-012-0787-1.CrossRef de Souza DL B, Jerez Roig J, Bernal MM: Laryngeal cancer survival in Zaragoza (Spain): a population-based study. Clin Transl Oncol. 2012, 14 (3): 221-224. 10.1007/s12094-012-0787-1.CrossRef
22.
go back to reference Liu Y, Dong XL, Tian C, Liu HG: Human telomerase RNA component (hTERC) gene amplification detected by FISH in precancerous lesions and carcinoma of the larynx. Diagn Pathol. 2012, 7: 34-10.1186/1746-1596-7-34.PubMedCentralCrossRefPubMed Liu Y, Dong XL, Tian C, Liu HG: Human telomerase RNA component (hTERC) gene amplification detected by FISH in precancerous lesions and carcinoma of the larynx. Diagn Pathol. 2012, 7: 34-10.1186/1746-1596-7-34.PubMedCentralCrossRefPubMed
23.
go back to reference Shi Y, Gong HL, Zhou L, Tian J, Wang Y: CD24: a novel cancer biomarker in laryngeal squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec. 2012, 74 (2): 78-85. 10.1159/000335584.CrossRefPubMed Shi Y, Gong HL, Zhou L, Tian J, Wang Y: CD24: a novel cancer biomarker in laryngeal squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec. 2012, 74 (2): 78-85. 10.1159/000335584.CrossRefPubMed
24.
go back to reference Liu J, Lei DP, Jin T, Zhao XN, Li G, Pan XL: Altered expression of miR-21 and PTEN in human laryngeal and hypopharyngeal squamous cell carcinomas. Asian Pac J Cancer Prev. 2011, 12 (10): 2653-2657.PubMed Liu J, Lei DP, Jin T, Zhao XN, Li G, Pan XL: Altered expression of miR-21 and PTEN in human laryngeal and hypopharyngeal squamous cell carcinomas. Asian Pac J Cancer Prev. 2011, 12 (10): 2653-2657.PubMed
25.
go back to reference Arrigo AP, Simon S, Gibert B, Kretz-Remy C, Nivon M, Czekalla A, Guillet D, Moulin M, Diaz-Latoud C, Vicart P: Hsp27 (HspB1) and alphaB-crystallin (HspB5) as therapeutic targets. FEBS Lett. 2007, 581 (19): 3665-3674. 10.1016/j.febslet.2007.04.033.CrossRefPubMed Arrigo AP, Simon S, Gibert B, Kretz-Remy C, Nivon M, Czekalla A, Guillet D, Moulin M, Diaz-Latoud C, Vicart P: Hsp27 (HspB1) and alphaB-crystallin (HspB5) as therapeutic targets. FEBS Lett. 2007, 581 (19): 3665-3674. 10.1016/j.febslet.2007.04.033.CrossRefPubMed
27.
go back to reference Chelouche-Lev D, Kluger HM, Berger AJ, Rimm DL, Price JE: alphaB-crystallin as a marker of lymphnode involvement in breast carcinoma. Cancer. 2004, 100 (12): 2543-2548. 10.1002/cncr.20304.CrossRefPubMed Chelouche-Lev D, Kluger HM, Berger AJ, Rimm DL, Price JE: alphaB-crystallin as a marker of lymphnode involvement in breast carcinoma. Cancer. 2004, 100 (12): 2543-2548. 10.1002/cncr.20304.CrossRefPubMed
28.
go back to reference Jeong WJ, Rho JH, Yoon YG, Yoo SH, Jeong NY, Ryu WY, Ahn HB, Park WC, Rho SH, Yoon HS, Choi YH, Yoo YH: Cytoplasmic and nuclear anti-apoptotic roles of αB-Crystallin in retinal pigment epithelial cells. PLoS One. 2012, 7 (9): e45754-10.1371/journal.pone.0045754.PubMedCentralCrossRefPubMed Jeong WJ, Rho JH, Yoon YG, Yoo SH, Jeong NY, Ryu WY, Ahn HB, Park WC, Rho SH, Yoon HS, Choi YH, Yoo YH: Cytoplasmic and nuclear anti-apoptotic roles of αB-Crystallin in retinal pigment epithelial cells. PLoS One. 2012, 7 (9): e45754-10.1371/journal.pone.0045754.PubMedCentralCrossRefPubMed
29.
go back to reference Huang Z, Cheng Y, Chiu PM, Cheung FM, Nicholls JM, Kwong DL, Lee AW, Zabarovsky ER, Stanbridge EJ, Lung HL, Lung ML: Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties. Oncogene. 2012, 31 (32): 3709-3720. 10.1038/onc.2011.529.CrossRefPubMed Huang Z, Cheng Y, Chiu PM, Cheung FM, Nicholls JM, Kwong DL, Lee AW, Zabarovsky ER, Stanbridge EJ, Lung HL, Lung ML: Tumor suppressor Alpha B-crystallin (CRYAB) associates with the cadherin/catenin adherens junction and impairs NPC progression-associated properties. Oncogene. 2012, 31 (32): 3709-3720. 10.1038/onc.2011.529.CrossRefPubMed
30.
go back to reference Barbash O, Zamfirova P, Lin DI, Chen X, Yang K, Nakagawa H, Lu F, Rustgi AK, Diehl JA: Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer. Cancer Cell. 2008, 14 (1): 68-78. 10.1016/j.ccr.2008.05.017.PubMedCentralCrossRefPubMed Barbash O, Zamfirova P, Lin DI, Chen X, Yang K, Nakagawa H, Lu F, Rustgi AK, Diehl JA: Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer. Cancer Cell. 2008, 14 (1): 68-78. 10.1016/j.ccr.2008.05.017.PubMedCentralCrossRefPubMed
31.
go back to reference Stronach EA, Sellar GC, Blenkiron C, Rabiasz GJ, Taylor KJ, Miller EP, Massie CE, Al-Nafussi A, Smyth JF, Porteous DJ, Gabra H: Identification of clinically relevant genes on chromosome 11 in a functional model of ovarian cancer tumor suppression. Cancer Res. 2003, 63 (24): 8648-8655.PubMed Stronach EA, Sellar GC, Blenkiron C, Rabiasz GJ, Taylor KJ, Miller EP, Massie CE, Al-Nafussi A, Smyth JF, Porteous DJ, Gabra H: Identification of clinically relevant genes on chromosome 11 in a functional model of ovarian cancer tumor suppression. Cancer Res. 2003, 63 (24): 8648-8655.PubMed
32.
go back to reference Solares CA, Boyle GM, Brown I, Parsons PG, Panizza B: Reduced alphaB-crystallin staining in perineural invasion of head and neck cutaneous squamous cell carcinoma. Otolaryngol Head Neck Surg. 2010, 142 (3 Suppl 1): S15-S19.CrossRefPubMed Solares CA, Boyle GM, Brown I, Parsons PG, Panizza B: Reduced alphaB-crystallin staining in perineural invasion of head and neck cutaneous squamous cell carcinoma. Otolaryngol Head Neck Surg. 2010, 142 (3 Suppl 1): S15-S19.CrossRefPubMed
33.
go back to reference Boslooper K, King-Yin Lam A, Gao J, Weinstein S, Johnson N: The clinicopathological roles of alpha-B-crystallin and p53 expression in patients with head and neck squamous cell carcinoma. Pathology. 2008, 40 (5): 500-504. 10.1080/00313020802198010.CrossRefPubMed Boslooper K, King-Yin Lam A, Gao J, Weinstein S, Johnson N: The clinicopathological roles of alpha-B-crystallin and p53 expression in patients with head and neck squamous cell carcinoma. Pathology. 2008, 40 (5): 500-504. 10.1080/00313020802198010.CrossRefPubMed
Metadata
Title
Alpha B-crystallin is a new prognostic marker for laryngeal squamous cell carcinoma
Authors
Yuan Mao
Da-Wei Zhang
Hong Lin
Lin Xiong
Ying Liu
Qing-Dong Li
Jun Ma
Qing Cao
Ren-Jie Chen
Jin Zhu
Zhen-Qing Feng
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2012
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-31-101

Other articles of this Issue 1/2012

Journal of Experimental & Clinical Cancer Research 1/2012 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine