Human Papilloma Viruses and Breast Cancer.
Human Papilloma Viruses and Breast Cancer.
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DOI：
10.3389/fonc.2015.00277
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发表时间：
2015
影响因子：
4.7
通讯作者：
Whitaker NJ
中科院分区：
文献类型：
--
作者：
Lawson JS;Glenn WK;Salyakina D;Delprado W;Clay R;Antonsson A;Heng B;Miyauchi S;Tran DD;Ngan CC;Lutze-Mann L;Whitaker NJ
人乳头瘤病毒（HPV）可能在某些乳腺癌中发挥作用。这项研究的目的是填补证据中的重要空白。这些差距是：（i）确认乳腺癌中存在癌症HPV的高风险，（ii）在相同患者中在HPV阳性乳腺癌发展之前在良性乳腺组织中HPV感染的证据，（iii）HPV在乳腺癌中是生物活性的并且不是无害乘客的证据。来自癌症基因组图谱（TCGA）的RNA-seq数据用于鉴定乳腺癌中的HPV RNA序列。我们还进行了一项基于聚合酶链反应（PCR）分析的回顾性队列研究，以确定澳大利亚良性乳腺活检妇女档案标本中的HPV，这些妇女后来患上了乳腺癌。为了评估乳腺癌中HPV是否具有生物活性，通过免疫组织化学（IHC）评估致癌蛋白HPV E7的表达。从TCGA数据库中的855例乳腺癌中确定了30种（3.5%）低风险和20种（2.3%）高风险HPV类型。高危型为HPV 18型（48%）、HPV 113型（24%）、HPV 16型（10%）、HPV 52型（10%）。PCR队列研究的数据表明，HPV 18型是乳腺癌标本中最常见的类型（40例乳腺癌标本中的55%），其次是HPV 16型（13%）。在15例良性乳腺癌和随后的乳腺癌中鉴定出相同的HPV类型。HPV E7蛋白在72%的良性乳腺标本和59%的浸润性乳腺癌标本中被鉴定。有四项特别令人感兴趣的意见：（i）通过NGS和PCR确认乳腺癌中高危HPV基因序列的存在，（ii）良性乳腺样本中高危HPV与同一患者中随后HPV阳性乳腺癌之间的相关性，（iii）乳腺癌中的HPV可能具有生物活性（如通过HPV DNA转录为RNA加上HPV E7蛋白的表达所示），（iv）HPV致癌影响可能在乳腺癌发展的早期发生。
Human papillomaviruses (HPV) may have a role in some breast cancers. The purpose of this study is to fill important gaps in the evidence. These gaps are: (i) confirmation of the presence of high risk for cancer HPVs in breast cancers, (ii) evidence of HPV infections in benign breast tissues prior to the development of HPV-positive breast cancer in the same patients, (iii) evidence that HPVs are biologically active and not harmless passengers in breast cancer. RNA-seq data from The Cancer Genome Atlas (TCGA) was used to identify HPV RNA sequences in breast cancers. We also conducted a retrospective cohort study based on polymerase chain reaction (PCR) analyses to identify HPVs in archival specimens from Australian women with benign breast biopsies who later developed breast cancer. To assess whether HPVs in breast cancer were biologically active, the expression of the oncogenic protein HPV E7 was assessed by immunohistochemistry (IHC). Thirty (3.5%) low-risk and 20 (2.3%) high-risk HPV types were identified in 855 breast cancers from the TCGA database. The high risk types were HPV 18 (48%), HPV 113 (24%), HPV 16 (10%), HPV 52 (10%). Data from the PCR cohort study indicated that HPV type 18 was the most common type identified in breast cancer specimens (55% of 40 breast cancer specimens) followed by HPV 16 (13%). The same HPV type was identified in both the benign and subsequent breast cancer in 15 patients. HPV E7 proteins were identified in 72% of benign breast specimens and 59% of invasive breast cancer specimens. There were four observations of particular interest: (i) confirmation by both NGS and PCR of the presence of high-risk HPV gene sequences in breast cancers, (ii) a correlation between high-risk HPV in benign breast specimens and subsequent HPV-positive breast cancer in the same patient, (iii) HPVs in breast cancer are likely to be biologically active (as shown by transcription of HPV DNA to RNA plus the expression of HPV E7 proteins), (iv) HPV oncogenic influences may occur early in the development of breast cancer.