The Effects of Autophagy-Related Genes and lncRNAs in Therapy and Prognosis of Colorectal Cancer.

Yang Yang,Weiting Liao,Mengxi Zhang,Kexun Zhou,Liangliang Bai,Mingyang Feng,Nan Zhang,Wanting Lei,Qiu Li,Jiaxing Huang

doi:10.3389/fonc.2021.582040

Yang Yang, Weiting Liao + Show 8 more

Open Access

https://doi.org/10.3389/fonc.2021.582040

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Abstract

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.

Highlights

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, with the top five morbidity and mortality rates in the world [1]
Gene enrichment analysis and signaling pathways by WebGestalt showed that differentially autophagy-related genes (DEAGs) played an important role in autophagy-related biological processes (Figures 1A–C) and signaling pathways (Figure 1D) in colorectal cancer (CRC) cells
In the process of CRC treatment, the enhancement of autophagy can make CRC cells survive under the stress state of lack of nutrition and energy, which strengthens the resistance to radiotherapy and chemotherapy

Summary

Introduction

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, with the top five morbidity and mortality rates in the world [1]. The main treatment methods of CRC are surgery, radiotherapy, and chemotherapy. As more research data being gathered, immunotherapy is gradually applied to treatment of CRC [2]. The current treatment solutions have extended the survival time of patients with CRC, the prognosis of patients is still not ideal. There are extensive researches regarding to the topics of accurate diagnosis, CRC treatment, and prognostic evaluation tools for the efficacy of tumor molecular drugs about chemotherapy, targeted therapy and immunotherapy in cancer [3]. The genetic information of cell autophagy can participate in the development of CRC and has good application prospects in diagnosis and treatment [4]. Whether cell autophagy has the potential for therapeutic efficacy and prognosis evaluation of CRC is not yet known

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