title: Reduced expression of autophagy markers correlates with high-risk human papillomavirus infection in human cervical squamous cell carcinoma.
abstract: Infection by an oncogenic human papillomavirus (HPV), in particular HPV16 and 18, is a high risk factor for developing cervical cancer; however, viral infection alone is not sufficient for cancer progression. Autophagy is hypothesized to be an important process during carcinogenesis. The aim of the present study was to investigate the association between autophagy and high-risk HPV (hrHPV) infection in human cervical squamous cell carcinomas (SCCs), and to analyze the clinical significance of this association. Quantum dot (QD)-based immunofluorescence histochemistry was used to detect the expression of autophagy markers, Beclin-1 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) proteins, in 104 cases of cervical cancer (including 80 SCCs and 24 adenocarcinomas) and 20 normal cervical tissues. hrHPV (HPV16/18) infection was detected by QDs based fluorescencein situhybridization in cervical cancers. The results revealed that the expression levels of Beclin-1 and LC3B were significantly lower in cervical cancer cells when compared with those of normal cervical squamous epithelial cells, and were found to negatively correlate with hrHPV infection. The expression levels of Beclin-1 and LC3B were not associated with age, tumor grade, tumor stage, tumor node metastasis stage or lymph node metastasis. However, a positive correlation was identified between Beclin-1 and LC3B protein expression. In addition, the absence of autophagy in combination with hrHPV infection may accelerate the progression of cervical SCC. In conclusion, decreased expression of Beclin-1 and LC3B may be important in cervical carcinogenesis. The hrHPV-host cell interaction may inhibit autophagy, which may aid virus duplication and infection, as well as cervical cancer development.
authors.affiliation: Department of Pathology, Jingzhou Second People's Hospital, Jingzhou, Hubei 434000, P.R. China.
authors.forename: Hua-Yi
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Gui-Fang
authors.initials: GF
authors.lastname: Yang
authors.affiliation: Department of Molecular Pathology, Wuhan Nano Tumor Diagnosis Engineering Research Center, Wuhan, Hubei 430075, P.R. China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Pathology, Jingzhou Second People's Hospital, Jingzhou, Hubei 434000, P.R. China.
authors.forename: Qi-Wen
authors.initials: QW
authors.lastname: Huang
authors.affiliation: Department of Molecular Pathology, Wuhan Nano Tumor Diagnosis Engineering Research Center, Wuhan, Hubei 430075, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Xian-DA
authors.initials: XD
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Huang
authors.affiliation: Department of Pathology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Hong-Lei
authors.initials: HL
authors.lastname: Chen
keywords: autophagy; beclin-1; cervical cancer; human papilloma virus; light chain 3B; quantum dots