Abstract
The upregulation of peroxisome proliferator-activated receptor gamma (PPARG) has been shown to increase the chemosensitivity of several human cancers. This study is aimed at studying if PPARG sensitizes hypopharyngeal squamous cell carcinoma (HSCC) in chemotherapeutic treatments and at dissecting possible mechanisms of observed effects. We integrated large-scale literature data and HSCC gene expression data to identify regulatory pathways that link PPARG and chemosensitivity in HSCC. Expression levels of molecules within the PPARG regulatory pathways were compared in 21 patients that underwent chemotherapy for primary HSCC, including 12 chemotherapy-sensitive patients (CSP) and 9 chemotherapy-nonsensitive patients (CNSP). In the CPS group, expression levels of PPARG were higher than that in the CNSP group (log‐fold‐change = 0.50). Structured text mining identified two chemosensitivity-related regulatory pathways driven by PPARG. In the CSP group, expression levels for 7 chemosensitivity-promoting genes were increased, while for 13 chemosensitivity suppressing the gene expression levels were decreased. Our results support the chemosensitivity-promoting role of PPARG in HSCC tumor cells, most likely by affecting both cell proliferation and cell motility pathways.
Highlights
As one of the most common head and neck tumors, hypopharyngeal squamous cell carcinoma (HSCC) accounts for more than 160,000 new cases and 83,000 deaths annually [1]
peroxisome proliferator-activated receptor gamma (PPARG) has been suggested as a target for chemoprevention in head and neck cancer prevention, which was based on consistent evidence from investigations of human tumor cell line studies, epidemiological analysis, and animal carcinogenesis models [8]
Our results suggested that the increased expression of PPARG might promote the chemosensitivity of HSCC cells through multiple molecular pathways
Summary
As one of the most common head and neck tumors, hypopharyngeal squamous cell carcinoma (HSCC) accounts for more than 160,000 new cases and 83,000 deaths annually [1]. In cell lines of oral carcinoma origin, the treatment with a synthetic retinoid, 4-hydroxyphenylretinamide was shown to result in an increase of HSCC chemosensitivity [7]. PPARG has been suggested as a target for chemoprevention in head and neck cancer prevention, which was based on consistent evidence from investigations of human tumor cell line studies, epidemiological analysis, and animal carcinogenesis models [8]. PPARG has been suggested as a potential therapeutic target gene for oral squamous cell carcinoma [9], and the activation of PPARG was shown to downregulate several features of the neoplastic phenotype in human upper aerodigestive tract tumors [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
