Yang Yang, Feng Mingyang, Bai LiangLiang, Zhang Mengxi, Zhou Kexun, Liao Weiting, Lei Wanting, Zhang Nan, Huang Jiaxing, Li Qiu
Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Sichuan, China.
West China Biomedical Big Data Center, Sichuan University, Sichuan, China.
Front Oncol. 2021 Mar 11;11:582040. doi: 10.3389/fonc.2021.582040. eCollection 2021.
Cellular autophagy plays an important role in the occurrence and development of colorectal cancer (CRC). Whether autophagy-related genes and lncRNAs can be used as ideal markers in CRC is still controversial. The purpose of this study is to identify novel treatment and prognosis markers of CRC. We downloaded transcription and clinical data of CRC from the GEO (GSE40967, GSE12954, GSE17536) and TCGA database, screened for differentially autophagy-related genes (DEAGs) and lncRNAs, constructed prognostic model, and analyzed its relationship with immune infiltration. TCGA and GEO datasets (GSE12954 and GSE17536) were used to validate the effect of the model. Oncomine database and Human Protein Atlas verified the expression of DEAGs. We obtained a total of 151 DEAGs in three verification sets collaboratively. Then we constructed a risk prognostic model through Lasso regression to obtain 15 prognostic DEAGs from the training set and verified the risk prognostic model in three verification sets. The low-risk group survived longer than the high-risk group. Age, gender, pathological stage, and TNM stage were related to the prognostic risk of CRC. On the other hand, BRAF status, RFS event, and tumor location are considered as most significant risk factors of CRC in the training set. Furthermore, we found that the immune score of the low-risk group was higher. The content of CD8 + T cells, active NK cells, macrophages M0, macrophages M1, and active dendritic cells was noted more in the high-risk group. The content of plasma cells, resting memory CD4 + T cells, resting NK cells, resting mast cells, and neutrophil cells was higher in the low-risk group. After all, the Oncomine database and immunohistochemistry verified that the expression level of most key autophagy-related genes was consistent with the results that we found. In addition, we obtained six lncRNAs co-expressed with DEAGs from the training set and found that the survival time was longer in the low-risk group. This finding was verified in the verification set and showed same trend to the results mentioned above. In the final analysis, these results indicate that autophagy-related genes and lncRNAs can be used as prognostic and therapeutic markers for CRC.
细胞自噬在结直肠癌（CRC）的发生发展中起重要作用。自噬相关基因和长链非编码RNA（lncRNAs）是否可作为CRC的理想标志物仍存在争议。本研究的目的是确定CRC新的治疗和预后标志物。我们从GEO（GSE40967、GSE12954、GSE17536）和TCGA数据库下载了CRC的转录和临床数据，筛选差异自噬相关基因（DEAGs）和lncRNAs，构建预后模型，并分析其与免疫浸润的关系。使用TCGA和GEO数据集（GSE12954和GSE17536）验证模型的效果。Oncomine数据库和人类蛋白质图谱验证了DEAGs的表达。我们在三个验证集中共获得151个DEAGs。然后通过Lasso回归构建风险预后模型，从训练集中获得15个预后DEAGs，并在三个验证集中验证风险预后模型。低风险组的生存期长于高风险组。年龄、性别、病理分期和TNM分期与CRC的预后风险相关。另一方面，BRAF状态、无复发生存期（RFS）事件和肿瘤位置被认为是训练集中CRC最显著的风险因素。此外，我们发现低风险组的免疫评分更高。高风险组中CD8 + T细胞、活化自然杀伤（NK）细胞、M0巨噬细胞、M1巨噬细胞和活化树突状细胞的含量更多。低风险组中浆细胞、静息记忆CD4 + T细胞、静息NK细胞、静息肥大细胞和中性粒细胞的含量更高。毕竟，Oncomine数据库和免疫组织化学验证了大多数关键自噬相关基因的表达水平与我们发现的结果一致。此外，我们从训练集中获得了6个与DEAGs共表达的lncRNAs，发现低风险组的生存时间更长。这一发现在验证集中得到验证，并与上述结果呈现相同趋势。最终分析表明，自噬相关基因和lncRNAs可作为CRC的预后和治疗标志物。
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