title: Low expression of claudin-4: an indicator of recurrence in esophageal squamous cell carcinoma after Ivor Lewis esophagectomy?
abstract: The high recurrence rate after surgery is the main reason for the poor prognosis of esophageal squamous cell carcinoma (ESCC) patients. Finding indicators of recurrence and taking adjuvant therapy may be useful for patients in high risk of recurrence. claudin-4 (CLDN4) is the core protein to form the tight junction, which plays an important role in cell adhesion, and its aberrant expression were detected in various cancers while its expression and functions in ESCC still remained unclear. Here, we detected the expression of CLDN4 in 114 ESCC tissue samples by real-time RT-PCR and immunohistochemistry, and the result showed that the low expression of CLDN4 correlated with a higher T staging (P = 0.010), lymphatic metastasis (P < 0.001) and recurrence status (P = 0.002). And the Cox regression analysis showed that the T classification (P = 0.005), lymph node metastasis (P = 0.003) and low CLDN4 expression (P = 0.029) were independent risk factors of recurrence. Further, we proved the CLDN4 in inhibiting growth, colony formation and invasion in vitro by establishing two stable CLDN4-silencing ESCC cell lines. In conclusion, CLDN4 played an important role in preventing metastasis and could be an effective biomarker to predict the recurrence of ESCC.
authors.affiliation: Department of Thoracic Surgery of Provincial Hospital, Shandong University, Jinan, 250021, China.
authors.forename: Mo
authors.initials: M
authors.lastname: Shi
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Song
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D002465:Cell Movement; D049109:Cell Proliferation; D062506:Claudin-4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D003114:Colony-Forming Units Assay; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016629:Esophagectomy / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C568157:CLDN4 protein, human; D062506:Claudin-4; D012333:RNA, Messenger; D034741:RNA, Small Interfering
references.citation: Hum Pathol. 2006 May;37(5):569-77
references.pmid: 16647955
references.citation: Ann Surg Oncol. 2013 Aug;20(8):2721-6
references.pmid: 23463093
references.citation: Ann Surg Oncol. 2011 Jan;18(1):273-81
references.pmid: 20839069
references.citation: World J Surg. 2007 May;31(5):1107-14
references.pmid: 17426905
references.citation: Ann Surg Oncol. 2012 Jul;19 Suppl 3:S491-9
references.pmid: 21837532
references.citation: Pathobiology. 2007;74(1):32-41
references.pmid: 17496431
references.citation: Front Biosci (Landmark Ed). 2011 Jan 01;16:1069-83
references.pmid: 21196219
references.citation: Prog Mol Biol Transl Sci. 2013;116:317-36
references.pmid: 23481201
references.citation: Gastric Cancer. 2009;12(1):43-51
references.pmid: 19390931
references.citation: Zhonghua Wai Ke Za Zhi. 2004 Jan 22;42(2):68-71
references.pmid: 15009981
references.citation: Lancet Oncol. 2007 Jun;8(6):545-53
references.pmid: 17540306
references.citation: Br J Surg. 2000 Oct;87(10):1426-33
references.pmid: 11044172
references.citation: Biomed Res. 2008 Apr;29(2):71-6
references.pmid: 18480547
references.citation: Cancer Res. 2003 Oct 1;63(19):6265-71
references.pmid: 14559813
references.citation: J Histochem Cytochem. 2011 Oct;59(10):932-41
references.pmid: 21832144
references.citation: Biochim Biophys Acta. 2009 Apr;1788(4):872-91
references.pmid: 19059202
references.citation: Acta Pharmacol Sin. 2011 May;32(5):552-64
references.pmid: 21499288
references.citation: Cancer Lett. 2013 Aug 28;337(1):41-8
references.pmid: 23743355
references.citation: J Am Coll Surg. 2000 Aug;191(2):143-8
references.pmid: 10945357
references.citation: Cancer Sci. 2011 Dec;102(12):2248-54
references.pmid: 21883696
references.citation: J Cell Physiol. 2007 Nov;213(2):374-83
references.pmid: 17680632
references.citation: Cancer Metastasis Rev. 2009 Jun;28(1-2):151-66
references.pmid: 19153669
references.citation: Mol Pharmacol. 2013 Jan;83(1):85-94
references.pmid: 23053666