Department of General Surgery II, the First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
Department of General Surgery, Wenshan people's Hospital of Yunnan Province, Yunnan, China.
Cancer Med. 2022 Dec;11(24):4900-4912. doi: 10.1002/cam4.4824. Epub 2022 May 19.
Stage IV colorectal cancer patients with liver metastasis represent a special group of CRC patients with poor prognosis. The prognostic factors have not been investigated for stage IV CRC patients undergoing primary cancer resection but not candidates for metastasis resection.
Ninety-nine stage IV CRC patients who underwent primary cancer resection without metastasis resection were retrospectively recruited. Both whole-exome sequencing (WES) and RNA-seq were performed with frozen primary cancer tissues, using para-cancerous normal tissues as the control. Valid data were obtained from 78 patients for WES and 84 patients for RNA-seq. Univariate, multivariate Cox analyses were performed and Nomogram model was established to predict patient prognosis.
The correlation between patient prognosis and clinicopathological factors, mutational status, or mRNA level changes was examined. Univariate (p = 0.0007) and subsequent multivariate analyses on clinicopathological factors showed that location (left or right) was the only independent risk factor for patient prognosis (HR = 3.63; 95% CI: 1.56-8.40, p = 0.003), while T, N, M staging, gender, race, location (rectum or colon), and pathological types were not stratifying factors. The mutational status of APC, TP53, KRAS, TTN, SYNE1, SMAD4, PIK3CA, RYR2, and BRAF did not show significant stratification in patient prognosis. RNA-seq showed that genes related to membrane function, ion channels, transporters, or receptors were among those with significant mRNA level alterations. Univariate analysis identified 97 genes with significantly altered mRNA levels, while NEUROD1, FGF18, SFTA2, PLAC1, SAA2, DSCAML1, and OTOP3 were significant in multivariate analysis. A risk model was established to stratify the prognosis of stage IV CRC patients. A Nomogram model was established with these genes to predict individual patient prognosis.
A panel of eight genes with significant mRNA level alterations was capable of predicting the prognosis and risk of the specific patient group. Future prospective study is needed to validate the model.
伴有肝转移的 IV 期结直肠癌患者是预后较差的一类 CRC 患者。对于未行转移灶切除术但不适合转移灶切除术的 IV 期 CRC 患者，其预后因素尚未得到研究。
回顾性招募了 99 例未行转移灶切除术而行原发灶切除术的 IV 期 CRC 患者。使用冷冻原发癌组织进行全外显子测序（WES）和 RNA-seq，以癌旁正常组织作为对照。WES 获得了 78 例患者的有效数据，RNA-seq 获得了 84 例患者的有效数据。进行单因素、多因素 Cox 分析，并建立诺莫图模型以预测患者预后。
检测了患者预后与临床病理因素、突变状态或 mRNA 水平变化的相关性。单因素（p=0.0007）和随后的临床病理因素多因素分析表明，位置（左或右）是患者预后的唯一独立危险因素（HR=3.63；95%CI：1.56-8.40，p=0.003），而 T、N、M 分期、性别、种族、位置（直肠或结肠）和病理类型不是分层因素。APC、TP53、KRAS、TTN、SYNE1、SMAD4、PIK3CA、RYR2 和 BRAF 的突变状态在患者预后中未显示出明显的分层。RNA-seq 显示，与膜功能、离子通道、转运体或受体相关的基因是那些具有显著 mRNA 水平改变的基因之一。单因素分析确定了 97 个 mRNA 水平显著改变的基因，而多因素分析中 NEUROD1、FGF18、SFTA2、PLAC1、SAA2、DSCAML1 和 OTOP3 具有显著意义。建立了一个风险模型来分层 IV 期 CRC 患者的预后。建立了一个基于这些基因的诺莫图模型来预测个体患者的预后。
一组具有显著 mRNA 水平改变的八个基因能够预测特定患者群体的预后和风险。需要进一步的前瞻性研究来验证该模型。
