Tumor-derived mutations in postoperative plasma of colorectal cancer with microsatellite instability.
Tumor-derived mutations in postoperative plasma of colorectal cancer with microsatellite instability.
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结直肠癌术后血浆中肿瘤衍生的微卫星不稳定性突变
DOI：
10.1016/j.tranon.2020.100945
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发表时间：
2021-01
影响因子：
5
通讯作者：
Wan D
中科院分区：
文献类型：
--
作者：
Li L;Zhou W;Li Q;Li P;Yang L;Xia X;Yi X;Wan D
MSI和MSS CRC肿瘤的分子特征有很大不同。MSI型结直肠癌术后血浆中的突变特征与MSS型结直肠癌有明显差异。在MSI中，应独立评估MSI结直肠癌术后血浆ctDNA的预后价值。术后血浆中的突变（分子残基）是结直肠癌（CRC）的独立预后因素。微卫星不稳定性（MSI）结直肠癌术后血浆突变的状态尚未得到系统的研究。在这项研究中，我们招募了30个MSI和46个微卫星稳定性（MSS）CRC，并对手术组织、术后血浆和随访期间的血浆进行了下一代测序。与MSS相比，MSI肿瘤具有不同的基因组谱，更高的肿瘤突变负荷（TMB）和更多的移码突变。在术后血浆中，检测到更多的具有肿瘤源性突变的MSI CRC（MSI中为77%，MSS中为33%，p < 0.001）。术后突变的数量与MSI组织成正比（斯皮尔曼r = 0.47，p = 0.023），而与MSS无关。MSI CRC的术后血浆样本中携带移码突变的比例高于MSS（p = 0.007）。对于随访血浆，93%（14/15）MSI CRC携带肿瘤源性突变; 33%（4/12）MSS为突变阳性，低于MSI（p = 0.003）。因此，考虑到MSI CRC与MSS CRC相比在肿瘤和术后血浆中具有非常不同的突变特征，我们建议在MSI和MSS CRC中独立评估术后血浆中分子残留鉴定的预后价值。
The molecular characteristics of MSI and MSS CRC tumors are quite different. MSI CRC postoperative plasma had distinct mutational characteristics with MSS CRC. The prognostic value of ctDNA in postoperative plasma of MSI CRC should be independently evaluated in MSI. The mutation in postoperative plasma (molecular residues) was an independently prognostic factor in colorectal cancer (CRC). The status of postoperative plasma mutation of microsatellite instability (MSI) CRC has not been systematically examined. In this study, we enrolled 30 MSI and 46 microsatellite stability (MSS) CRCs, and performed next generation sequencing on surgical tissues, postoperative plasma, and plasma during follow-up. Compared with MSS, MSI tumors had dissimilar genomic profiles, higher tumor mutation burden (TMB), and more frameshift mutations. In the postoperative plasma, more MSI CRCs were detected with tumor-derived mutations (77% in MSI vs 33% in MSS, p < 0.001). The numbers of postoperative mutations were proportional to MSI tissues (Spearman r = 0.47, p = 0.023), while not for MSS. More proportion of postoperative plasma samples of MSI CRCs harbored frameshift mutations than MSS (p = 0.007). For the follow-up plasma, 93% (14 out of 15) MSI CRCs harbored tumor-derived mutations; 33% (4/12) MSS were mutation-positive, lower than MSI (p = 0.003). Thus, considering that MSI CRC had extremely distinct mutational characteristics in tumor and postoperative plasma compared with MSS CRC, we propose that the prognostic value of molecular residue identification in postoperative plasma needs to be independently evaluated in MSI and MSS CRCs.
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影响因子：
16.6
作者：
Sausen M;Phallen J;Adleff V;Jones S;Leary RJ;Barrett MT;Anagnostou V;Parpart-Li S;Murphy D;Kay Li Q;Hruban CA;Scharpf R;White JR;O'Dwyer PJ;Allen PJ;Eshleman JR;Thompson CB;Klimstra DS;Linehan DC;Maitra A;Hruban RH;Diaz LA Jr;Von Hoff DD;Johansen JS;Drebin JA;Velculescu VE
通讯作者：
Velculescu VE
影响因子：
24.5
作者：
Jass, JR;Do, KA;Leggett, B
通讯作者：
Leggett, B
影响因子：
28.4
作者：
Reinert, Thomas;Henriksen, Tenna Vesterman;Andersen, Claus Lindbjerg
通讯作者：
Andersen, Claus Lindbjerg
影响因子：
2.1
作者：
Fabrizio, David A.;George, Thomas J., Jr.;Klempner, Samuel J.
通讯作者：
Klempner, Samuel J.
影响因子：
4.1
作者：
Shia, Jinru
通讯作者：
Shia, Jinru