Academic Journal
View in EDS

Relationship between concentration of heavy metals in bladder cancer tissue and molecular types using luminal GATA3 and basal cytokeratin 5/6 markers.

Bibliographic Details
Title: Relationship between concentration of heavy metals in bladder cancer tissue and molecular types using luminal GATA3 and basal cytokeratin 5/6 markers.
Authors: Ali-El-Dein B; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Electronic address: balieldein@yahoo.com., Abdelgawad M; Toshka Urology and Endoscopy center, Mansoura, Egypt., Abdel-Rahim M; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Gomaa IM; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Elnaggar II; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Zahran F; Department of Biochemistry, Faculty of science, Zagazig University, Egypt., Salama AF; Department of Biochemistry, Faculty of science, Tanta University, Egypt., Keshta AT; Department of Biochemistry, Faculty of science, Zagazig University, Egypt., Mohamed AE; Department of Biochemistry, Faculty of science, Tanta University, Egypt., Saleh HH; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Mortada WI; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Attia AM; Forensic and Toxicology Department, Faculty of Medicine, Mansoura University, Egypt., Elkady ME; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Source: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) [J Trace Elem Med Biol] 2026 Oct; Vol. 97, pp. 127944. Date of Electronic Publication: 2026 Aug 20.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Gustav Fisher Country of Publication: Germany NLM ID: 9508274 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-3252 (Electronic) Linking ISSN: 0946672X NLM ISO Abbreviation: J Trace Elem Med Biol Subsets: MEDLINE
Imprint Name(s): Publication: Stuttgart : Gustav Fisher
Original Publication: Stuttgart ; New York : Gustav Fischer, c1995-
MeSH Terms: GATA3 Transcription Factor*/metabolism , GATA3 Transcription Factor*/genetics , Urinary Bladder Neoplasms*/metabolism , Urinary Bladder Neoplasms*/pathology , Metals, Heavy*/analysis , Metals, Heavy*/metabolism , Biomarkers, Tumor*/metabolism , Biomarkers, Tumor*/genetics , Keratin-6*/metabolism , Keratin-6*/genetics , Keratin-5*/metabolism , Keratin-5*/genetics, Humans ; Male ; Female ; Aged ; Middle Aged ; Aged, 80 and over
Abstract: Introduction and Objectives: Data on molecular sub-typing of bladder cancer (BC) associated with heavy metals (HMTE) are lacking. Clinical significance of luminal (GATA3) and basal (cytokeratin 5/6) markers in BC is controversial. Therefore, objective is to use these markers to characterize BC associated with HMTE into luminal and basal, and to investigate their clinical significance.
Methods: Study included 143 patients undergoing radical cystectomy (RC) for urothelial carcinoma. Two fresh samples were obtained from cancerous and non-cancerous RC specimens to measure [aluminum-Al, cadmium-Cd, cobalt-Co, chromium-Cr, copper-Cu, iron-Fe, nickel-Ni, lead-Pb, zinc-Zn] concentration and GATA3,CK5,CK6, by ICP-OES and RT-PCR, respectively. Also, histopathology and immunohistochemistry for GATA3/CK5/6 were performed.
Results: Stage was pT1/pT2/pT3/pT4 in 36/17/75/15 and grade was G1/G2/G3 in 26/32/85 patients, respectively. High Cd, Co, Cr, Ni, and/or Pb concentration in BC tissue was associated with high CK5/6 and lower GATA3 expression. High GATA3 was associated with low stages, low grade and negative lymph nodes (LN), while high CK5/6 expression was associated with the reverse. Cu had antagonistic effects to (Cd, Co, Cr, Ni, Pb) regarding both markers. No significant association was found between Fe or Zn and GATA3or CK5/6 expression.
Conclusions: High BC tissue concentration of Cd, Co, Cr, Ni, and/or Pb has been proved to be associated with high expression of the basal Cytokeratin 5/6 and lower expression of luminal marker GATA3. High GATA3 and CK5/6 expression are associated with favorable (low stages, low grade, negative LN) and aggressive BC, respectively. However, data on cancer specific survival are awaited.
(Copyright © 2026 Elsevier GmbH. All rights reserved.)
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bedeir Ali-El-Dein reports financial support was provided by Egyptian Science and Technology Development Fund. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Contributed Indexing: Keywords: Bladder cancer; Cytokeratin; GATA3; Heavy metals; Molecular types
Substance Nomenclature: 0 (GATA3 Transcription Factor)
0 (Metals, Heavy)
0 (GATA3 protein, human)
0 (Biomarkers, Tumor)
0 (Keratin-6)
0 (Keratin-5)
Entry Date(s): Date Created: 20260822 Date Completed: 20260918 Latest Revision: 20260918
Update Code: 20260919
DOI: 10.1016/j.jtemb.2026.127944
PMID: 42632153
Database: MEDLINE
FullText Text:
  Availability: 0
CustomLinks:
  – Url: https://www.doi.org/10.1016/j.jtemb.2026.127944?
    Name: ScienceDirect (all content) (s7799221)
    Category: fullText
    Text: View record from ScienceDirect
    MouseOverText: View record from ScienceDirect
  – Url: https://resolver.ebsco.com/c/fiv2js/result?sid=EBSCO:cmedm&genre=article&issn=18783252&ISBN=&volume=97&issue=&date=20261001&spage=127944&pages=127944&title=Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)&atitle=Relationship%20between%20concentration%20of%20heavy%20metals%20in%20bladder%20cancer%20tissue%20and%20molecular%20types%20using%20luminal%20GATA3%20and%20basal%20cytokeratin%205%2F6%20markers.&aulast=Ali-El-Dein%20B&id=DOI:10.1016/j.jtemb.2026.127944
    Name: Full Text Finder (for New FTF UI) (ns324271)
    Category: fullText
    Text: Full Text Finder
    MouseOverText: Full Text Finder
Header DbId: cmedm
DbLabel: MEDLINE
An: 42632153
AccessLevel: 3
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Relationship between concentration of heavy metals in bladder cancer tissue and molecular types using luminal GATA3 and basal cytokeratin 5/6 markers.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AU" term="%22Ali-El-Dein+B%22">Ali-El-Dein B</searchLink>; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt. Electronic address: balieldein@yahoo.com.<br /><searchLink fieldCode="AU" term="%22Abdelgawad+M%22">Abdelgawad M</searchLink>; Toshka Urology and Endoscopy center, Mansoura, Egypt.<br /><searchLink fieldCode="AU" term="%22Abdel-Rahim+M%22">Abdel-Rahim M</searchLink>; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.<br /><searchLink fieldCode="AU" term="%22Gomaa+IM%22">Gomaa IM</searchLink>; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.<br /><searchLink fieldCode="AU" term="%22Elnaggar+II%22">Elnaggar II</searchLink>; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.<br /><searchLink fieldCode="AU" term="%22Zahran+F%22">Zahran F</searchLink>; Department of Biochemistry, Faculty of science, Zagazig University, Egypt.<br /><searchLink fieldCode="AU" term="%22Salama+AF%22">Salama AF</searchLink>; Department of Biochemistry, Faculty of science, Tanta University, Egypt.<br /><searchLink fieldCode="AU" term="%22Keshta+AT%22">Keshta AT</searchLink>; Department of Biochemistry, Faculty of science, Zagazig University, Egypt.<br /><searchLink fieldCode="AU" term="%22Mohamed+AE%22">Mohamed AE</searchLink>; Department of Biochemistry, Faculty of science, Tanta University, Egypt.<br /><searchLink fieldCode="AU" term="%22Saleh+HH%22">Saleh HH</searchLink>; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.<br /><searchLink fieldCode="AU" term="%22Mortada+WI%22">Mortada WI</searchLink>; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.<br /><searchLink fieldCode="AU" term="%22Attia+AM%22">Attia AM</searchLink>; Forensic and Toxicology Department, Faculty of Medicine, Mansoura University, Egypt.<br /><searchLink fieldCode="AU" term="%22Elkady+ME%22">Elkady ME</searchLink>; Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%229508274%22">Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)</searchLink> [J Trace Elem Med Biol] 2026 Oct; Vol. 97, pp. 127944. <i>Date of Electronic Publication: </i>2026 Aug 20.
– Name: TypePub
  Label: Publication Type
  Group: TypPub
  Data: Journal Article
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: TitleSource
  Label: Journal Info
  Group: Src
  Data: <i>Publisher: </i><searchLink fieldCode="PB" term="%22Gustav+Fisher%22">Gustav Fisher </searchLink><i>Country of Publication: </i>Germany <i>NLM ID: </i>9508274 <i>Publication Model: </i>Print-Electronic <i>Cited Medium: </i>Internet <i>ISSN: </i>1878-3252 (Electronic) <i>Linking ISSN: </i><searchLink fieldCode="IS" term="%220946672X%22">0946672X </searchLink><i>NLM ISO Abbreviation: </i>J Trace Elem Med Biol <i>Subsets: </i>MEDLINE
– Name: PublisherInfo
  Label: Imprint Name(s)
  Group: PubInfo
  Data: <i>Publication</i>: Stuttgart : Gustav Fisher<br /><i>Original Publication</i>: Stuttgart ; New York : Gustav Fischer, c1995-
– Name: SubjectMESH
  Label: MeSH Terms
  Group: Su
  Data: <searchLink fieldCode="MM" term="%22GATA3+Transcription+Factor%22">GATA3 Transcription Factor*</searchLink>/<searchLink fieldCode="MM" term="%22GATA3+Transcription+Factor+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22GATA3+Transcription+Factor%22">GATA3 Transcription Factor*</searchLink>/<searchLink fieldCode="MM" term="%22GATA3+Transcription+Factor+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Urinary+Bladder+Neoplasms%22">Urinary Bladder Neoplasms*</searchLink>/<searchLink fieldCode="MM" term="%22Urinary+Bladder+Neoplasms+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Urinary+Bladder+Neoplasms%22">Urinary Bladder Neoplasms*</searchLink>/<searchLink fieldCode="MM" term="%22Urinary+Bladder+Neoplasms+pathology%22">pathology</searchLink> <br /><searchLink fieldCode="MM" term="%22Metals%2C+Heavy%22">Metals, Heavy*</searchLink>/<searchLink fieldCode="MM" term="%22Metals%2C+Heavy+analysis%22">analysis</searchLink> <br /><searchLink fieldCode="MM" term="%22Metals%2C+Heavy%22">Metals, Heavy*</searchLink>/<searchLink fieldCode="MM" term="%22Metals%2C+Heavy+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Biomarkers%2C+Tumor%22">Biomarkers, Tumor*</searchLink>/<searchLink fieldCode="MM" term="%22Biomarkers%2C+Tumor+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Biomarkers%2C+Tumor%22">Biomarkers, Tumor*</searchLink>/<searchLink fieldCode="MM" term="%22Biomarkers%2C+Tumor+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Keratin-6%22">Keratin-6*</searchLink>/<searchLink fieldCode="MM" term="%22Keratin-6+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Keratin-6%22">Keratin-6*</searchLink>/<searchLink fieldCode="MM" term="%22Keratin-6+genetics%22">genetics</searchLink> <br /><searchLink fieldCode="MM" term="%22Keratin-5%22">Keratin-5*</searchLink>/<searchLink fieldCode="MM" term="%22Keratin-5+metabolism%22">metabolism</searchLink> <br /><searchLink fieldCode="MM" term="%22Keratin-5%22">Keratin-5*</searchLink>/<searchLink fieldCode="MM" term="%22Keratin-5+genetics%22">genetics</searchLink><br /><searchLink fieldCode="MH" term="%22Humans%22">Humans</searchLink> ; <searchLink fieldCode="MH" term="%22Male%22">Male</searchLink> ; <searchLink fieldCode="MH" term="%22Female%22">Female</searchLink> ; <searchLink fieldCode="MH" term="%22Aged%22">Aged</searchLink> ; <searchLink fieldCode="MH" term="%22Middle+Aged%22">Middle Aged</searchLink> ; <searchLink fieldCode="MH" term="%22Aged%2C+80+and+over%22">Aged, 80 and over</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Introduction and Objectives: Data on molecular sub-typing of bladder cancer (BC) associated with heavy metals (HMTE) are lacking. Clinical significance of luminal (GATA3) and basal (cytokeratin 5/6) markers in BC is controversial. Therefore, objective is to use these markers to characterize BC associated with HMTE into luminal and basal, and to investigate their clinical significance.<br />Methods: Study included 143 patients undergoing radical cystectomy (RC) for urothelial carcinoma. Two fresh samples were obtained from cancerous and non-cancerous RC specimens to measure [aluminum-Al, cadmium-Cd, cobalt-Co, chromium-Cr, copper-Cu, iron-Fe, nickel-Ni, lead-Pb, zinc-Zn] concentration and GATA3,CK5,CK6, by ICP-OES and RT-PCR, respectively. Also, histopathology and immunohistochemistry for GATA3/CK5/6 were performed.<br />Results: Stage was pT1/pT2/pT3/pT4 in 36/17/75/15 and grade was G1/G2/G3 in 26/32/85 patients, respectively. High Cd, Co, Cr, Ni, and/or Pb concentration in BC tissue was associated with high CK5/6 and lower GATA3 expression. High GATA3 was associated with low stages, low grade and negative lymph nodes (LN), while high CK5/6 expression was associated with the reverse. Cu had antagonistic effects to (Cd, Co, Cr, Ni, Pb) regarding both markers. No significant association was found between Fe or Zn and GATA3or CK5/6 expression.<br />Conclusions: High BC tissue concentration of Cd, Co, Cr, Ni, and/or Pb has been proved to be associated with high expression of the basal Cytokeratin 5/6 and lower expression of luminal marker GATA3. High GATA3 and CK5/6 expression are associated with favorable (low stages, low grade, negative LN) and aggressive BC, respectively. However, data on cancer specific survival are awaited.<br /> (Copyright © 2026 Elsevier GmbH. All rights reserved.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bedeir Ali-El-Dein reports financial support was provided by Egyptian Science and Technology Development Fund. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
– Name: SubjectMinor
  Label: Contributed Indexing
  Group:
  Data: <i>Keywords: </i>Bladder cancer; Cytokeratin; GATA3; Heavy metals; Molecular types
– Name: NumberCAS
  Label: Substance Nomenclature
  Group: ID
  Data: 0 (GATA3 Transcription Factor)<br />0 (Metals, Heavy)<br />0 (GATA3 protein, human)<br />0 (Biomarkers, Tumor)<br />0 (Keratin-6)<br />0 (Keratin-5)
– Name: DateEntry
  Label: Entry Date(s)
  Group: Date
  Data: <i>Date Created: </i>20260822 <i>Date Completed: </i>20260918 <i>Latest Revision: </i>20260918
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20260919
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1016/j.jtemb.2026.127944
– Name: AN
  Label: PMID
  Group: ID
  Data: 42632153
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42632153
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1016/j.jtemb.2026.127944
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 127944
    Subjects:
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Male
        Type: general
      – SubjectFull: Female
        Type: general
      – SubjectFull: Aged
        Type: general
      – SubjectFull: Middle Aged
        Type: general
      – SubjectFull: Aged, 80 and over
        Type: general
      – SubjectFull: GATA3 Transcription Factor metabolism
        Type: general
      – SubjectFull: GATA3 Transcription Factor genetics
        Type: general
      – SubjectFull: Urinary Bladder Neoplasms metabolism
        Type: general
      – SubjectFull: Urinary Bladder Neoplasms pathology
        Type: general
      – SubjectFull: Metals, Heavy analysis
        Type: general
      – SubjectFull: Metals, Heavy metabolism
        Type: general
      – SubjectFull: Biomarkers, Tumor metabolism
        Type: general
      – SubjectFull: Biomarkers, Tumor genetics
        Type: general
      – SubjectFull: Keratin-6 metabolism
        Type: general
      – SubjectFull: Keratin-6 genetics
        Type: general
      – SubjectFull: Keratin-5 metabolism
        Type: general
      – SubjectFull: Keratin-5 genetics
        Type: general
    Titles:
      – TitleFull: Relationship between concentration of heavy metals in bladder cancer tissue and molecular types using luminal GATA3 and basal cytokeratin 5/6 markers.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Ali-El-Dein B
      – PersonEntity:
          Name:
            NameFull: Abdelgawad M
      – PersonEntity:
          Name:
            NameFull: Abdel-Rahim M
      – PersonEntity:
          Name:
            NameFull: Gomaa IM
      – PersonEntity:
          Name:
            NameFull: Elnaggar II
      – PersonEntity:
          Name:
            NameFull: Zahran F
      – PersonEntity:
          Name:
            NameFull: Salama AF
      – PersonEntity:
          Name:
            NameFull: Keshta AT
      – PersonEntity:
          Name:
            NameFull: Mohamed AE
      – PersonEntity:
          Name:
            NameFull: Saleh HH
      – PersonEntity:
          Name:
            NameFull: Mortada WI
      – PersonEntity:
          Name:
            NameFull: Attia AM
      – PersonEntity:
          Name:
            NameFull: Elkady ME
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 10
              Text: 2026 Oct
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1878-3252
          Numbering:
            – Type: volume
              Value: 97
          Titles:
            – TitleFull: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
              Type: main
ResultId 1