Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection
Song Qing,
Wuniqiemu Tulake,
Mingfang Ru,
Xiaohong Li,
Reziwanguli Yuemaier,
Dilare Lidifu,
Aierken Rouzibilali,
Axiangu Hasimu,
Yun Yang,
Reziya Rouziahong,
Halmurat Upur,
Abulizi Abudula
Affiliations
Song Qing
Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, P.R. China
Wuniqiemu Tulake
Key Laboratory of Chinese Ministry of Education and Xinjiang Uighur Autonomous Region for High-Incident Diseases in Uighur Ethnic Population, Xinjiang Medical University, Urumqi, P.R. China
Mingfang Ru
Department of Gynecology, The Third Affiliated Hospital of Xinjiang Medical University, Urumqi, P.R. China
Xiaohong Li
Department of Gynecology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, P.R. China
Reziwanguli Yuemaier
Key Laboratory of Chinese Ministry of Education and Xinjiang Uighur Autonomous Region for High-Incident Diseases in Uighur Ethnic Population, Xinjiang Medical University, Urumqi, P.R. China
Dilare Lidifu
Key Laboratory of Chinese Ministry of Education and Xinjiang Uighur Autonomous Region for High-Incident Diseases in Uighur Ethnic Population, Xinjiang Medical University, Urumqi, P.R. China
Aierken Rouzibilali
Key Laboratory of Chinese Ministry of Education and Xinjiang Uighur Autonomous Region for High-Incident Diseases in Uighur Ethnic Population, Xinjiang Medical University, Urumqi, P.R. China
Axiangu Hasimu
Key Laboratory of Chinese Ministry of Education and Xinjiang Uighur Autonomous Region for High-Incident Diseases in Uighur Ethnic Population, Xinjiang Medical University, Urumqi, P.R. China
Yun Yang
Key Laboratory of Chinese Ministry of Education and Xinjiang Uighur Autonomous Region for High-Incident Diseases in Uighur Ethnic Population, Xinjiang Medical University, Urumqi, P.R. China
Reziya Rouziahong
Key Laboratory of Chinese Ministry of Education and Xinjiang Uighur Autonomous Region for High-Incident Diseases in Uighur Ethnic Population, Xinjiang Medical University, Urumqi, P.R. China
Halmurat Upur
Key Laboratory of Chinese Ministry of Education and Xinjiang Uighur Autonomous Region for High-Incident Diseases in Uighur Ethnic Population, Xinjiang Medical University, Urumqi, P.R. China
Abulizi Abudula
Key Laboratory of Chinese Ministry of Education and Xinjiang Uighur Autonomous Region for High-Incident Diseases in Uighur Ethnic Population, Xinjiang Medical University, Urumqi, P.R. China
It is known that high-risk human papillomavirus infection is the main etiological factor in cervical carcinogenesis. However, human papillomavirus screening is not sufficient for early diagnosis. In this study, we aimed to identify potential biomarkers common to cervical carcinoma and human papillomavirus infection by proteomics for human papillomavirus–based early diagnosis and prognosis. To this end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical intraepithelial neoplasia II–III, or normal cervix from ethnic Uighur and Han women. Human papillomavirus infection by eight oncogenic human papillomavirus types was detected in tissue DNA samples using a quantitative polymerase chain reaction. The protein profile of cervical specimens from human papillomavirus 16–positive squamous cell carcinoma and human papillomavirus–negative normal controls was analyzed by proteomics and bioinformatics. The expression of candidate proteins was further determined by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We identified 67 proteins that were differentially expressed in human papillomavirus 16–positive squamous cell carcinoma compared to normal cervix. The quantitative reverse transcriptase-polymerase chain reaction analysis verified the upregulation of ASAH1 , PCBP2 , DDX5 , MCM5 , TAGLN2 , hnRNPA1 , ENO1 , TYPH , CYC , and MCM4 in squamous cell carcinoma compared to normal cervix ( p < 0.05). In addition, the transcription of PCBP2 , MCM5 , hnRNPA1 , TYPH , and CYC was also significantly increased in cervical intraepithelial neoplasia II–III compared to normal cervix. Immunohistochemistry staining further confirmed the overexpression of PCBP2, hnRNPA1, ASAH1, and DDX5 in squamous cell carcinoma and cervical intraepithelial neoplasia II–III compared to normal controls ( p < 0.05). Our data suggest that the expression of ASAH1, PCBP2, DDX5, and hnRNPA1, and possibly MCM4, MCM5, CYC, ENO1, and TYPH, is upregulated during cervical carcinogenesis and potentially associated with human papillomavirus infection. Further validation studies of the profile will contribute to establishing auxiliary diagnostic markers for human papillomavirus–based cancer prognosis.
