Autophagy, an evolutionary and conservative multistage lysosomal degradation process that promotes metabolism and healthy circulation, plays a complex and contradictory role in tumor formation and cancer treatment . As a subclass of the ncRNAs family, lncRNAs play an indispensable role in various biological processes of tumorigenesis, which are considered a new type of biomarker for cancer diagnosis and prognosis widely concerned . The current researches were mainly focused on the function of single or a few lncRNAs involved in autophagy in HCC patients [32–34]. Therefore, it is necessary to explore more autophagy-related lncRNAs to predict HCC patients' prognosis.
In our study, autophagy-related lncRNAs were obtained by establishing the co-expression network of lncRNAs and autophagy genes. Univariate and multivariate Cox regression analyses were used to obtain the 7 prognostic autophagy-related lncRNAs, including PRRT3-AS1, RP11-479G22.8, RP11-73M18.8, LINC01138, CTD-2510F5.4, and RP11-324I22.4, and CTC-297N7.9.The seven autophagy-related lncRNAs may become prognostic molecular markers and potential therapeutic targets for HCC patients for follow-up research.
On the one hand, as the only beneficial prognostic lncRNA in the prognostic prediction model. ,the gene alias of CTC-297N7.9 is lnc-TMEM220-1, which is an intergenic ncRNA. An HCC study showed that CTC-297N7.9 might be related to cofactor/chromatin/NAD binding and oxidoreductase/DNA-dependent ATPase activity . Besides, due to the specific low expression and high methylation of TMEM220 in gastric cancer tissues , some scholars speculate that CTC-297N7.9 that located upstream of the protein-coding gene TMEM220, may be able to regulate the methylation of TMEM220 or participate in autophagy through its functional proteins, which in turn affects the prognosis of HCC patients . In our research, we have speculated that the highly expressed CTC-297N7.9 may be an inhibitory factor in the progression of HCC. This speculation was confirmed in another study on liver cancer, and the high expression of CTC-297N7.9 often predicts better overall survival and disease-free survival  and indicates that CTC-297N7.9 may be one of the critical molecules to improve HCC patients' survival, and it can be further explored in subsequent studies on HCC.
On the other hand, the 6 unfavorable prognostic lncRNAs in the prognostic prediction model have also been attached to various cancers. The official full name of PRRT3-AS1 is PRRT3 antisense RNA 1, as a non-protein-coding RNA, which is mainly expressed in liver tissue (RPKM 0.15), fat (RPKM 4.4), prostate (RPKM 3.3), and brain tissue (RPKM 3.0) . In prostate cancer, Fan et al. confirmed that PRRT3-AS1 has a targeting relationship with PPARγ. Its silence can promote apoptosis autophagy and inhibit the proliferation, migration, and invasion of tumor cells through the mTOR signaling pathway . Besides, PRRT3-AS1 is also considered to be related to GBM patients' prognosis . RP11-479G22.8 is also known as lnc-ITGB1-1 in the LNCipedia database , and its transcription size is 2051 bp. Through the lncRNA disease prediction module of the lncRNASNP2 database , RP11-479G22.8 is closely related to HCC (P < 0.001). Therefore, RP11-479G22.8 is expected to be one of the potential indicators for prognostic prediction in HCC patients . RP11-73M18.8 is a sense-intronic lncRNA with a transcript size of 811 bp, also known as lnc-ZFYVE21-3. Sense-intronic lncRNA is a sequence in the intron of the coding gene on the sense strand. It might harbor different histone modification at the transcription start site (TSS) than other ncRNAs , which indicated that these intronic lncRNAs maybe the novel biomarkers, such as type 2 diabetes mellitus . LINC01138 is also a member of the sense intron ncRNA, located on chr1. Its abnormal expression has an important influence on the occurrence and development of several cancers. In prostate cancer (PCa), as a lncRNA that directly target AR, the high expression of LINC01138 can promote the proliferation of tumor cells and inhibit their apoptosis, which indicated that LINC01138 could be a diagnostic and prognostic marker for PCa . Besides, LINC01138 can increase the arginine methylation and protein stability of sterol regulatory element-binding protein one by interacting with PRMT5, thereby promoting lipid desaturation and cell proliferation in clear cell renal cell carcinoma and being associated with poor prognosis. However. The knockdown of LINC01138 can inhibit the viability, proliferation, invasion, and migration and promotes apoptosis of gastric cancer cells through the LINC01138/miR-1273e/MAPK axis .In some studies related to HCC, high-expressed LINC01138 is not only significantly associated with poor survival  but also can interact with arginine methyltransferase 5 to promote cell proliferation, tumorigenicity, tumor invasion, and metastasis . CTD-2510F5.4 is a 321 bp antisense lncRNA, also known as lnc-SKA2-1 in the LNCipedia database. Through the NPInter v4.0 database , we found that CTD-2510F5.4 mainly interacts with genes in the mRNA surveillance pathway and RNA transport pathway. The high expressed CTD-2510F5.4 also has a significant co-expression relationship with mRNAs of the cell cycle, DNA replication, and p53 signaling pathway . It is closely related to the poor prognosis of patients with lung adenocarcinoma. In gastric cancer, the highly expressed CTD-2510F5.4 may be an independent risk factor for tumors with pathological grade < III and no vascular or nerve infiltration . RP11-324I22.4 is an antisense lncRNA; the gene alias is lnc-CUL2-3. As cancer or tumor suppressor genes, antisense lncRNAs play an essential role in the occurrence and development of human cancer[55–57]. Although there is currently no disease research related to RP11-324I22.4, antisense lncRNAs may certainly be the promising tumor biomarker and therapeutic target in future research.
The risk scoring model we identified ( AUC of 1-, 3-, and 5-year were 0.853, 0.794, and 0.764, respectively ) is more reliable than a similar study in HCC (AUC of the 1-, 3-, and 5-year survival are 0.764, 0.738, and 0.717, respectively) , but it still has its limitations. This study is only based on the TCGA database, and there are no suitable datasets in other databases to verify the risk prediction model. Furthermore, the research is only conducted at the level of bioinformatics; a comprehensive in vitro experiment is needed further to explore the regulatory mechanism of these autophagy lncRNAs.