子宫颈癌胃型腺癌TP53基因及其通路改变。

IF 4.1 Q2 ONCOLOGY
Daiki Higuchi, Maiko Yamaguchi, Erisa Fujii, Mayumi Kobayashi Kato, Kengo Hiranuma, Yuka Asami, Hanako Ono, Takafumi Koyama, Masaaki Komatsu, Ryuji Hamamoto, Yasuhisa Terao, Koji Matsumoto, Akihiko Sekizawa, Mitsuya Ishikawa, Takashi Kohno, Hiroshi Yoshida, Hideki Makinoshima, Kouya Shiraishi, Tomoyasu Kato
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引用次数: 0

摘要

人乳头瘤病毒(HPV)感染有助于几乎所有宫颈恶性肿瘤的发展,除了胃型宫颈腺癌(GAS),一种罕见的侵袭性亚型,没有HPV感染。为了研究这种疾病的致癌机制,我们在三个独立的GAS和UEA患者队列中对GAS和普通型宫颈内膜腺癌(UEA)进行了比较多组学分析。第一个队列包括2002年至2020年间在国家癌症中心医院接受治疗的8名GAS和22名UEA患者,他们通过靶向和全转录组测序进行了检查。另外两个队列包括52例GAS和109例UEA患者,39例GAS和232例UEA患者,其突变数据分别来自C-CAT(日本患者)和GENIE(美国患者)公共数据库。对8例患者进行代谢组学分析,其中5例为GAS。在所有三个队列中,TP53突变在GAS中比在UEA中更普遍。转录组分析一致显示GAS中tp53相关通路的频繁抑制。在GAS组织中优先检测到的代谢物表明TP53的改变与肿瘤内代谢特性有关。GAS的发展可能是由TP53突变驱动的,TP53突变在形成肿瘤细胞内的细胞内信号传导和代谢谱中起着重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

TP53 gene and pathway alterations in gastric-type adenocarcinoma of the cervix.

TP53 gene and pathway alterations in gastric-type adenocarcinoma of the cervix.

TP53 gene and pathway alterations in gastric-type adenocarcinoma of the cervix.

TP53 gene and pathway alterations in gastric-type adenocarcinoma of the cervix.

Background: Human papillomavirus infection contributes to the development of almost all cervical malignancies, aside from gastric-type adenocarcinoma of the cervix, a rare aggressive subtype without human papillomavirus infection.

Methods: To address the carcinogenic mechanism of this disease, we performed a comparative multi-omics analysis of gastric-type adenocarcinoma of the cervix and usual-type endocervical adenocarcinoma in 3 independent cohorts of patients with gastric-type adenocarcinoma of the cervix and usual-type endocervical adenocarcinoma. The first cohort comprised 8 gastric-type adenocarcinoma of the cervix and 22 patients with usual-type endocervical adenocarcinoma treated at the National Cancer Center Hospital between 2002 and 2020, who were examined by targeted and whole transcriptome sequencing. The other 2 cohorts comprised 52 patients with gastric-type adenocarcinoma of the cervix and 109 patients with usual-type endocervical adenocarcinoma and 39 patients with gastric-type adenocarcinoma of the cervix and 232 patients with usual-type endocervical adenocarcinoma, whose mutational data were obtained from the Center for Cancer Genomics and Advanced Therapeutics (Japanese patients) and Genomics Evidence Neoplasia Information Exchange (US patients) public databases, respectively. Metabolomic analysis was performed in 8 patients, including 5 with gastric-type adenocarcinoma of the cervix.

Results: TP53 mutations were more prevalent in gastric-type adenocarcinoma of the cervix than in usual-type endocervical adenocarcinoma in all 3 cohorts. Transcriptome analysis consistently revealed frequent suppression of TP53-related pathways in gastric-type adenocarcinoma of the cervix. Metabolites preferentially detected in gastric-type adenocarcinoma of the cervix tissues suggest TP53 alterations are implicated in intratumoral metabolic properties.

Conclusion: The development of gastric-type adenocarcinoma of the cervix is likely driven by TP53 mutations, which play a large role in shaping intracellular signaling and metabolic profiles within tumor cells.

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来源期刊
JNCI Cancer Spectrum
JNCI Cancer Spectrum Medicine-Oncology
CiteScore
7.70
自引率
0.00%
发文量
80
审稿时长
18 weeks
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