Wang Hua-Yi, Yang Gui-Fang, Huang Yan-Hua, Huang Qi-Wen, Gao Jun, Zhao Xian-DA, Huang Li-Ming, Chen Hong-Lei
Department of Pathology, Jingzhou Second People's Hospital, Jingzhou, Hubei 434000, P.R. China.
Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
Oncol Lett. 2014 Oct;8(4):1492-1498. doi: 10.3892/ol.2014.2417. Epub 2014 Aug 5.
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 fluorescence hybridization 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.
致癌性人乳头瘤病毒(HPV)感染,尤其是HPV16和18感染,是宫颈癌发生的高风险因素;然而,仅病毒感染不足以导致癌症进展。自噬被认为是致癌过程中的一个重要过程。本研究的目的是探讨人宫颈鳞状细胞癌(SCC)中自噬与高危型HPV(hrHPV)感染之间的关联,并分析这种关联的临床意义。采用基于量子点(QD)的免疫荧光组织化学方法,检测104例宫颈癌(包括80例SCC和24例腺癌)及20例正常宫颈组织中自噬标志物Beclin-1和微管相关蛋白1A/1B轻链3B(LC3B)蛋白的表达。通过基于量子点的荧光杂交法检测宫颈癌中的hrHPV(HPV16/18)感染。结果显示,与正常宫颈鳞状上皮细胞相比,宫颈癌细胞中Beclin-1和LC3B的表达水平显著降低,且发现与hrHPV感染呈负相关。Beclin-1和LC3B的表达水平与年龄、肿瘤分级、肿瘤分期、肿瘤淋巴结转移分期或淋巴结转移无关。然而,Beclin-1与LC3B蛋白表达之间存在正相关。此外,自噬缺失与hrHPV感染共同作用可能加速宫颈SCC的进展。总之,Beclin-1和LC3B表达降低可能在宫颈癌发生过程中起重要作用。hrHPV与宿主细胞的相互作用可能抑制自噬,这可能有助于病毒复制和感染以及宫颈癌的发展。