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具核梭杆菌的预后影响取决于辅助化疗治疗的II/III期结直肠癌的肿瘤位置与微卫星不稳定性状态的联合情况。

Prognostic Impact of Fusobacterium nucleatum Depends on Combined Tumor Location and Microsatellite Instability Status in Stage II/III Colorectal Cancers Treated with Adjuvant Chemotherapy.

作者信息

Oh Hyeon Jeong, Kim Jung Ho, Bae Jeong Mo, Kim Hyun Jung, Cho Nam-Yun, Kang Gyeong Hoon

机构信息

Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

出版信息

J Pathol Transl Med. 2019 Jan;53(1):40-49. doi: 10.4132/jptm.2018.11.29. Epub 2018 Dec 26.

Abstract

BACKGROUND

This study aimed to investigate the prognostic impact of intratumoral Fusobacterium nucleatum in colorectal cancer (CRC) treated with adjuvant chemotherapy.

METHODS

F. nucleatumDNA was quantitatively measured in a total of 593 CRC tissues retrospectively collectedfrom surgically resected specimens of stage III or high-risk stage II CRC patients who had receivedcurative surgery and subsequent oxaliplatin-based adjuvant chemotherapy (either FOLFOXor CAPOX). Each case was classified into one of the three categories: F. nucleatum-high, -low, or -negative.

RESULTS

No significant differences in survival were observed between the F.nucleatum-high and -low/negative groups in the 593 CRCs (p = .671). Subgroup analyses accordingto tumor location demonstrated that disease-free survival was significantly better in F.nucleatum-high than in -low/negative patients with non-sigmoid colon cancer (including cecal,ascending, transverse, and descending colon cancers; n = 219; log-rank p = .026). In multivariateanalysis, F. nucleatum was determined to be an independent prognostic factor in non-sigmoidcolon cancers (hazard ratio, 0.42; 95% confidence interval, 0.18 to 0.97; p = .043). Furthermore,the favorable prognostic effect of F. nucleatum-high was observed only in a non-microsatellite instability-high (non-MSI-high) subset of non-sigmoid colon cancers (log-rank p = 0.014), but not ina MSI-high subset (log-rank p = 0.844), suggesting that the combined status of tumor locationand MSI may be a critical factor for different prognostic impacts of F. nucleatum in CRCs treatedwith adjuvant chemotherapy.

CONCLUSIONS

Intratumoral F. nucleatum load is a potential prognosticfactor in a non-MSI-high/non-sigmoid/non-rectal cancer subset of stage II/III CRCs treatedwith oxaliplatin-based adjuvant chemotherapy.

摘要

背景

本研究旨在探讨瘤内具核梭杆菌对接受辅助化疗的结直肠癌(CRC)患者预后的影响。

方法

回顾性收集了593例CRC组织样本,这些样本来自接受了根治性手术及随后基于奥沙利铂的辅助化疗(FOLFOX或CAPOX)的III期或高危II期CRC患者的手术切除标本。对具核梭杆菌DNA进行定量检测。每个病例被分为以下三类之一:具核梭杆菌高、低或阴性。

结果

在593例CRC患者中,具核梭杆菌高表达组与低表达/阴性组之间的生存率无显著差异(p = 0.671)。根据肿瘤位置进行的亚组分析表明,具核梭杆菌高表达的非乙状结肠癌患者(包括盲肠、升结肠、横结肠和降结肠癌;n = 219;对数秩检验p = 0.026)的无病生存期显著优于具核梭杆菌低表达/阴性患者。在多变量分析中,具核梭杆菌被确定为非乙状结肠癌的独立预后因素(风险比,0.42;95%置信区间,0.18至0.97;p = 0.043)。此外,仅在非乙状结肠癌的非微卫星高度不稳定(非MSI-High)亚组中观察到具核梭杆菌高表达的良好预后作用(对数秩检验p = 0.014),而在MSI-High亚组中未观察到(对数秩检验p = 0.844),这表明肿瘤位置和MSI的联合状态可能是具核梭杆菌对接受辅助化疗的CRC患者预后产生不同影响的关键因素。

结论

瘤内具核梭杆菌负荷是接受基于奥沙利铂的辅助化疗的II/III期CRC患者的非MSI-High/非乙状/非直肠癌亚组中的一个潜在预后因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8cd0/6344805/e9d9ba9b62de/jptm-2018-11-29f1.jpg

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