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牙龈卟啉单胞菌感染会加重食道癌,并促进对新辅助化疗的耐药性。

Porphyromonas gingivalis infection exacerbates oesophageal cancer and promotes resistance to neoadjuvant chemotherapy.

机构信息

Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology (HAUST), Luoyang, China.

Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA.

出版信息

Br J Cancer. 2021 Aug;125(3):433-444. doi: 10.1038/s41416-021-01419-5. Epub 2021 May 12.

Abstract

BACKGROUND

The effect of Porphyromonas gingivalis (Pg) infection on oesophageal squamous cell carcinoma (ESCC) prognosis, chemotherapeutic efficacy, and oesophageal cancer cell apoptosis resistance and proliferation remain poorly understood.

METHODS

Clinicopathological data from 312 ESCC oesophagectomy patients, along with the computed tomography imaging results and longitudinal cancerous tissue samples from a patient subset (n = 85) who received neoadjuvant chemotherapy (NACT), were analysed. Comparison of overall survival and response rate to NACT between Pg-infected and Pg-uninfected patients was made by multivariate Cox analysis and Response Evaluation Criteria in Solid Tumours v.1.1 criteria. The influence of Pg on cell proliferation and drug-induced apoptosis was examined in ESCC patients and validated in vitro and in vivo.

RESULTS

The 5-year overall survival was lower in Pg-positive patients, and infection was associated with multiple clinicopathological factors and pathologic tumour, node, metastasis stage. Of the 85 patients who received NACT, Pg infection was associated with a lower response rate and 5-year overall survival. Infection with Pg resulted in apoptosis resistance in ESCC and promoted ESCC cell viability, which was confirmed in longitudinal cancerous tissue samples. Pg-induced apoptosis resistance was dependent on fimbriae and STAT3.

CONCLUSIONS

Pg infection is associated with a worse ESCC prognosis, reduced chemotherapy efficacy, and can potentiate the aggressive behaviour of ESCC cells.

摘要

背景

牙龈卟啉单胞菌(Pg)感染对食管鳞状细胞癌(ESCC)预后、化疗疗效以及食管癌细胞凋亡抵抗和增殖的影响仍知之甚少。

方法

分析了 312 例接受食管切除术的 ESCC 患者的临床病理数据,以及接受新辅助化疗(NACT)的患者亚组(n=85)的计算机断层扫描成像结果和纵向癌组织样本。通过多变量 Cox 分析和实体瘤反应评价标准 1.1 对 Pg 感染和未感染患者的总生存率和 NACT 反应率进行比较。在 ESCC 患者中并在体外和体内验证了 Pg 对细胞增殖和药物诱导的细胞凋亡的影响。

结果

Pg 阳性患者的 5 年总生存率较低,感染与多种临床病理因素和病理肿瘤、淋巴结、转移分期相关。在接受 NACT 的 85 例患者中,Pg 感染与较低的反应率和 5 年总生存率相关。Pg 感染导致 ESCC 细胞凋亡抵抗,并促进 ESCC 细胞活力,这在纵向癌组织样本中得到了证实。Pg 诱导的凋亡抵抗依赖于菌毛和 STAT3。

结论

Pg 感染与 ESCC 预后较差、化疗疗效降低有关,并能增强 ESCC 细胞的侵袭性行为。

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