Axl and autophagy LC3 expression in tumors is strongly associated with clinical prognosis of hepatocellular carcinoma patients after curative resection

Hsu, Chia‐Chang; Hsieh, Pei‐Min; Chen, Yaw‐Sen; Lo, Gin‐Ho; Lin, Hung‐Yu; Dai, Chia‐Yen; Huang, Jee‐Fu; Chuang, Wan‐Long; Chen, Yao‐Li; Yu, Ming‐Lung; Lin, Chih‐Wen

doi:10.1002/cam4.2229

Cited by 21 publications

(28 citation statements)

References 22 publications

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“…Studies have shown that abberrant expression of Beclin-1 is strongly associated with the poor survival of various tumors such as intrahepatic cholangiocarcinoma ( 19 ), endometrial adenocarcinoma ( 20 ), colorectal cancer ( 21 ). LC3 was found to be related to tumor growth and progression of triple negative breast cancer ( 22 ), and be associated with clinical prognosis of pancreatic cancer ( 23 ), hepatocellular carcinoma ( 24 ) and colorectal cancer ( 25 ). Our study found that 127 and 131 ATGs were closely related to the OS of LGG patients from the TCGA and CGGA datasets, among which a total of 80 ATGs were present in both groups.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of an Autophagy-Related Five-Gene Signature for Lower-Grade Glioma Patients

Guo

Wei

et al. 2021

Front. Oncol.

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Background: Molecular characteristics can be good indicators of tumor prognosis and have been introduced into the classification of gliomas. The prognosis of patients with newly classified lower-grade gliomas (LGGs, including grade 2 and grade 3 gliomas) is highly heterogeneous, and new molecular markers are urgently needed.Methods: Autophagy related genes (ATGs) were obtained from Human Autophagy Database (HADb). From the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), gene expression profiles including ATG expression information and patient clinical data were downloaded. Cox regression analysis, receiver operating characteristic (ROC) analysis, Kaplan–Meier analysis, random survival forest algorithm (RSFVH) and stratification analysis were performed.Results: Through univariate Cox regression analysis, we found a total of 127 ATGs associated with the prognosis of LGG patients from TCGA dataset and a total of 131 survival-related ATGs from CGGA dataset. Using TCGA dataset as the training group (n = 524), we constructed a five-ATG signature (including BAG1, BID, MAP1LC3C, NRG3, PTK6), which could divide LGG patients into two risk groups with significantly different overall survival (Log Rank P < 0.001). Then we confirmed in the independent CGGA dataset that the five-ATG signature had the ability to predict prognosis (n = 431, Log Rank P < 0.001). We further discovered that the predictive ability of the five-ATG signature was better than the existing clinical indicators and IDH mutation status. In addition, the five-ATG signature could further classify patients after receiving radiotherapy or chemotherapy into groups with different prognosis.Conclusions: We identified a five-ATG signature that could be a reliable prognostic marker and might be therapeutic targets for autophagy therapy for LGG patients.

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Section: Discussionmentioning

confidence: 99%

Prognostic Value of an Autophagy-Related Five-Gene Signature for Lower-Grade Glioma Patients

Guo

Wei

et al. 2021

Front. Oncol.

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“…Recently, the high LC3 expression, by immunohistochemistry analysis, both in the tumour and non-tumour liver was significantly associated with lower HCC recurrence in patients who underwent curative hepatectomy for HCC [ 60 ]. Therefore, LC3 was also considered a potential marker for predicting HCC recurrence and overall survival [ 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

Gene and protein expression of mTOR and LC3 in hepatocellular carcinoma, colorectal liver metastasis and “normal” liver tissues

et al. 2020

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The physiological role of autophagy in the progression of liver diseases is still debated. To understand the clinical relevance of autophagy in primary e secondary hepatic tumors, we analyzed the expression of mTOR (mammalian target of rapamycin), a key regulator of autophagy; Raptor (regulatory-associated protein of mTOR); ULK1 (Unc-51 like kinase 1) determinant in the autophagy initiation; LC3 (microtubule-associated protein 1A/1B-light chain 3), a specific marker of autophagosomes; and p62, a selective autophagy receptor. Samples from subjects with chronic hepatitis (n.58), cirrhosis (n.12), hepatocellular carcinoma (HCC, n.56), metastases (n.48) from colorectal cancer and hyperplasia or gallbladder stones (n.7), the latter considered as controls, were examined. Gene expression analysis was carried out in n.213 tissues by absolute q-PCR, while protein expression by Western Blot in n.191 lysates, including tumoral, surrounding tumoral and normal tissues. Nonparametric statistical tests were used for comparing expression levels in the above-mentioned groups. Subgroup analysis was performed considering viral infection and chemotherapy treatment. The mTOR transcriptional level was significantly lower in metastases compared to HCC (P = 0.0001). p-mTOR(Ser2448) and LC3II/LC3I protein levels were significantly higher in metastases compared to HCC (P = 0.008 and P<0.0001, respectively). ULK(Ser757) levels were significantly higher in HCC compared to metastases (P = 0.0002) while the HCV- and HBV- related HCC showed the highest p62 levels. Chemotherapy induced a down-regulation of the p-mTOR(Ser2448) in metastases and in non-tumor surrounding tissues in treated patients compared to untreated (P = 0.001 and P = 0.005, respectively). Conclusions: the different expression of proteins considered, owning their interaction and diverse tissue microenvironment, indicate an impairment of the autophagy flux in primary liver tumors that is critical for the promotion of tumorigenesis process and a coexistence of autophagy inhibition and activation mechanisms in secondary liver tumors. Differences in mTOR and LC3 transcripts emerged in tumor-free tissues, therefore particular attention should be considered in selecting the control group.

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“…A meta-analysis involving 949 patients in HCC indicated that positive LC3 expression was related to the size of the tumor and the occurrence of HCC 45 . However, the combination of high Axl and low LC3 expression could significantly predict poorer prognosis for HCC patients who underwent hepatectomy in HCC 46 . Other data demonstrate that the complex involvement of TIPRL/LC3/CD133 in HCC aggressiveness can serve as potential biomarkers for early detection in a combined model or worked individually 47 .…”

Section: Autophagy and Autophagy-related Proteins In Hccmentioning

confidence: 97%

Autophagy, an accomplice or antagonist of drug resistance in HCC?

Zhang

Qin

2021

Cell Death Dis

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Hepatocellular carcinoma (HCC) is a highly lethal malignancy characterized by poor prognosis and a low 5-year survival rate. Drug treatment is proving to be effective in anti-HCC. However, only a small number of HCC patients exhibit sensitive responses, and drug resistance occurs frequently in advanced patients. Autophagy, an evolutionary process responsible for the degradation of cellular substances, is closely associated with the acquisition and maintenance of drug resistance for HCC. This review focuses on autophagic proteins and explores the intricate relationship between autophagy and cancer stem cells, tumor-derived exosomes, and noncoding RNA. Clinical trials involved in autophagy inhibition combined with anticancer drugs are also concerned.

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Axl and autophagy LC3 expression in tumors is strongly associated with clinical prognosis of hepatocellular carcinoma patients after curative resection

Cited by 21 publications

References 22 publications

Prognostic Value of an Autophagy-Related Five-Gene Signature for Lower-Grade Glioma Patients

Prognostic Value of an Autophagy-Related Five-Gene Signature for Lower-Grade Glioma Patients

Gene and protein expression of mTOR and LC3 in hepatocellular carcinoma, colorectal liver metastasis and “normal” liver tissues

Autophagy, an accomplice or antagonist of drug resistance in HCC?

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