Open AccessCharacterization of key transcription factors as molecular signatures of HPV ‐positive and HPV ‐negative oral cancers
Author(s) -
Verma Gaurav,
Vishnoi Kanchan,
Tyagi Abhishek,
Jadli Mohit,
Singh Tejveer,
Goel Ankit,
Sharma Ankita,
Agarwal Kiran,
Prasad Subhash Chandra,
Pandey Durgatosh,
Sharma Shashi,
Mehrotra Ravi,
Singh Sukh Mahendra,
Bharti Alok Chandra
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.983
Subject(s) - junb , medicine , immunohistochemistry , cancer research , transcription factor , activator (genetics) , nf κb , biology , receptor , gene , inflammation , genetics
Prior studies established constitutively active AP ‐1, NF ‐ κ B, and STAT 3 signaling in oral cancer. Differential expression/activation of specific members of these transcription factors has been documented in HPV ‐positive oral lesions that respond better to therapy. We performed a comprehensive analysis of differentially expressed, transcriptionally active members of these pivotal signaling mediators to develop specific signatures of HPV ‐positive and HPV ‐negative oral lesions by immunohistochemical method that is applicable in low‐resource settings. We examined a total of 31 prospective and 30 formalin‐fixed, paraffin‐embedded tissues from treatment‐naïve, histopathologically and clinically confirmed cases diagnosed as oral or oropharyngeal squamous cell carcinoma ( OSCC / OPSCC ). Following determination of their HPV status by GP 5 + / GP 6 + PCR , the sequential sections of the tissues were evaluated for expression of JunB, JunD, c‐Fos, p50, p65, STAT 3, and pSTAT 3(Y705), along with two key regulatory proteins pEGFR and p16 by IHC . Independent analysis of JunB and p65 showed direct correlation with HPV positivity, whereas STAT 3 and pSTAT 3 were inversely correlated. A combined analysis of transcription factors revealed a more restrictive combination, characterized by the presence of AP ‐1 and NF ‐ κ B lacking involvement of STAT 3 that strongly correlated with HPV ‐positive tumors. Presence of STAT 3/ pSTAT 3 with NF ‐ κ B irrespective of the presence or absence of AP ‐1 members was present in HPV ‐negative lesions. Expression of pSTAT 3 strongly correlated with all the AP ‐1/ NF ‐ κ B members (except JunD), its upstream activator pEGFR Y 1092 , and HPV infection‐related negative regulator p16. Overall, we show a simple combination of AP ‐1, NF ‐ κ B, and STAT 3 members’ expression that may serve as molecular signature of HPV ‐positive lesions or more broadly the tumors that show better prognosis.