Identification of CDCA2 as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma

ObjectiveHepatocellular carcinoma (HCC) is one of the most common and malignant tumors with an insidious onset, difficult early diagnosis, and limited therapy options, resulting in a poor prognosis. Cell division cycle associated 2 (CDCA2), also known as Repo-Man, plays an important role in regulating mitosis and DNA repair, but the involvement of CDCA2 in HCC remains unclear.MethodsThe differentially expressed genes that were significantly upregulated in multiple RNA sequencing datasets of HCC were screened. Receiver operating characteristic (ROC) curve analysis was performed to identify diagnostic markers for HCC. Least absolute shrinkage and selection operator Cox regression analysis was performed to screen the prognosis-related genes. The screening and analyses identified CDCA2 as the target gene in this study. The expression of CDCA2 was analyzed in public databases and clinical specimens, and CDCA2 involvement in HCC was explored by both bioinformatic analysis and in vitro experiments.ResultsThe level of CDCA2 was enhanced in HCC compared with healthy livers. Overexpression of CDCA2 positively correlated with the pathological grade and TNM stage of the diseases. Furthermore, CDCA2 was found to be an independent prognostic predictor. An excellent prognostic model of HCC was successfully constructed with CDCA2 in combination with TNM stage. Bioinformatic analysis revealed that CDCA2 was closely associated with the cell cycle, apoptosis, and p53 signaling pathway. Silencing CDCA2 in Huh7 cells resulted in significant upregulation of p53 and the downstream PUMA and NOXA and a subsequently increased apoptosis. Inhibition of p53 signaling and apoptosis was found after overexpression of CDCA2 in L02 cells. Strikingly, the proliferation of cells was not affected by CDCA2.ConclusionsCDCA2 was a novel diagnostic marker for HCC, and overexpression of this gene reflected poor pathological grade, stage, and clinical prognosis. CDCA2 promoted the pathogenesis of HCC by suppressing the p53-PUMA/NOXA signaling and the subsequent apoptosis.

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Integrated Analysis of lncRNA-Mediated ceRNA Network Reveals a Prognostic Signature for Hepatocellular Carcinoma

Frontiers in Genetics ◽

10.3389/fgene.2020.602542 ◽

2020 ◽

Vol 11 ◽

Author(s):

Jian-Rong Sun ◽

Chen-Fan Kong ◽

Kun-Min Xiao ◽

Jia-Lu Yang ◽

Xiang-Ke Qu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Regression Analysis ◽

Cox Regression ◽

Tnm Stage ◽

The Cancer Genome Atlas ◽

Integrated Analysis ◽

Cox Regression Analysis ◽

Cerna Network ◽

Kaplan Meier ◽

Risk Patients

Hepatocellular carcinoma (HCC) is one of the most common types of malignancy and is associated with high mortality. Prior research suggests that long non-coding RNAs (lncRNAs) play a crucial role in the development of HCC. Therefore, it is necessary to identify lncRNA-associated therapeutic biomarkers to improve the accuracy of HCC prognosis. Transcriptomic data of HCC obtained from The Cancer Genome Atlas (TCGA) database were used in the present study. Differentially expressed RNAs (DERNAs), including 74 lncRNAs, 16 miRNAs, and 35 mRNAs, were identified using bioinformatics analysis. The DERNAs were subsequently used to reconstruct a competing endogenous RNA (ceRNA) network. A lncRNA signature was revealed using Cox regression analysis, including LINC00200, MIR137HG, LINC00462, AP002478.1, and HTR2A-AS1. Kaplan-Meier plot demonstrated that the lncRNA signature is highly accurate in discriminating high- and low-risk patients (P < 0.05). The area under curve (AUC) value exceeded 0.7 in both training and validation cohort, suggesting a high prognostic potential of the signature. Furthermore, multivariate Cox regression analysis indicated that both the TNM stage and the lncRNA signature could serve as independent prognostic factors for HCC (P < 0.05). Then, a nomogram comprising the TNM stage and the lncRNA signature was determined to raise the accuracy in predicting the survival of HCC patients. In the present study, we have introduced a ceRNA network that could contribute to provide a new insight into the identification of potential regulation mechanisms for the development of HCC. The five-lncRNA signature could serve as a reliable biosignature for HCC prognosis, while the nomogram possesses strong potential in clinical applications.

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Enhanced expression of miR-889 forecasts an unfavorable prognosis and facilitates cell progression in hepatocellular carcinoma

Diagnostic Pathology ◽

10.1186/s13000-021-01111-5 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

He Wang ◽

Huiwen Wang ◽

Wenyu Cui ◽

Qiao Zhang ◽

Jing Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Cell Lines ◽

Cox Regression ◽

Malignant Tumors ◽

Prognostic Significance ◽

High Expression ◽

Migration And Invasion ◽

Pcr Analysis ◽

Cox Regression Analysis

Abstract Background As a new type of molecular marker, microRNAs (miRNAs) can be used for early diagnosis and prognosis prediction of malignant tumors, and has broad clinical application prospects. This paper mainly studies the important role of miR-889 in the occurrence and development of hepatocellular carcinoma and the prognostic significance of miR-889 in hepatocellular carcinoma. Methods Quantitative real-time PCR analysis detected the expression levels of miR-889 in hepatocellular carcinoma tissues and cell lines. Kaplan-Meier curve and Cox regression analysis were used to explore the prognostic significance of miR-889 in hepatocellular carcinoma. The CCK-8 and Transwell assays assay were used to assess cell proliferation, migration, and invasion abilities ability. Results The expression of miR-889 in hepatocellular carcinoma tissues was significantly higher than that in adjacent tissues. Overexpression of miR-889 was significantly associated with TNM stage, hepatitis B virus infection, and cirrhosis. Patients with high miR-889 expression had shorter overall survival than those with low miR-889 expression. And functional studies in two hepatocellular carcinoma cell lines have shown that overexpression of miR-889 significantly promoted cell proliferation, migration, and invasion in vitro. Conclusions Overall, miR-889 was upregulated in hepatocellular carcinoma tissues and cell lines, and overexpression of miR-889 promoted cell proliferation, migration, and invasion in hepatocellular carcinoma cells. Based on our findings, high expression of miR-889 may promote the progression of hepatocellular carcinoma, and high expression of miR-889 is also forecasted for an unfavorable prognosis in hepatocellular carcinoma.

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A Novel Five-gene Signature Predicts Overall Survival in Hepatocellular Carcinoma

10.21203/rs.3.rs-32144/v1 ◽

2020 ◽

Author(s):

Zhigang Wang ◽

Leyu Pan ◽

Deliang Guo ◽

Xiaofeng Luo ◽

Jie Tang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Regression Analysis ◽

Cox Regression ◽

Gene Signature ◽

Tnm Stage ◽

Time Dependent ◽

Quantitative Real Time Pcr ◽

Cox Regression Analysis ◽

Normal Tissues

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common challenges for public health worldwide. Due to its complex molecular and great heterogeneity, the effectiveness of existing HCC risk prediction models is unsatisfactory. Hence, more accurate prognostic models are pressingly needed. Materials and methods: Differentially expressed mRNAs (DEMs) between HCC and normal tissues were identified after downloading GSE1450 from gene omnibus (GEO) database. We randomly divided all patients into training and testing sets. Univariate Cox regression, lasso Cox regression and multivariable Cox regression analysis were used to constructed the prognostic gene signature in training set. Our study utilized Kaplan-Meier plot, time-dependent receiver operating characteristic (ROC), multivariable Cox regression analysis with clinical information, nomogram and decision curve analysis (DCA) to evaluate the predictive ability for overall survival of the novel gene signature in training, testing and whole sets. We also validated the prognostic capacity of the five-gene signature in an external validation set. The information of mutation of each gene was explored on cBioPortal online website. We performed gene set enrichment analysis (GSEA) to explore underlying mechanisms in the high and low risk group. Finally, quantitative real-time PCR was conducted to validate the expression tendency between 12 paired HCC and adjacent normal tissues. Results: Our study constructed a novel five-gene signature (CNIH4, SOX4, SPP1, SORBS2 and CCL19) for predicting overall survival of HCC. Time-dependent ROC curve indicated admirable ability in survival prediction in two datasets. Multivariable Cox regression analysis indicated that both this five-gene signature and TNM stage were two independent prognostic factors for overall survival of HCC patients. Combined with TNM stage clinical pathological parameters, the predictive capacity of nomogram had a decent improvement. The mutation of the five genes had no obvious variation. Plenty pathways were enriched by GSEA, including cell cycle and various metabolism. Furthermore, the mRNA levels of these five genes had signiﬁcantly diﬀerent expressions between HCC tissues and adjacent normal tissues by quantitative real-time PCR. Conclusions: A five-gene prognostic model and nomogram were constructed and validated for predicting prognostic of HCC patients. And the five-gene risk score with TNM stage models might help various HCC patients to customize individual therapies.

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Gene signatures and prognostic values of m1A-related regulatory genes in hepatocellular carcinoma

Scientific Reports ◽

10.1038/s41598-020-72178-1 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Qingmiao Shi ◽

Chen Xue ◽

Xin Yuan ◽

Yuting He ◽

Zujiang Yu

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Enrichment Analysis ◽

Cancer Genome ◽

Regulatory Genes ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Clinical Prognosis ◽

Cox Regression Analysis ◽

Genes Expression

Abstract Hepatocellular carcinoma (HCC) ranks fourth in cancer-related mortality worldwide. N1-methyladenosine (m1A), a methylation modification on RNA, is gaining attention for its role across diverse biological processes. However, m1A-related regulatory genes expression, its relationship with clinical prognosis, and its role in HCC remain unclear. In this study, we utilized The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database to investigate alterations within 10 m1A-related regulatory genes and observed a high mutation frequency (23/363). Cox regression analysis and least absolute shrinkage and selection operator were used to explore the association between m1A-related regulatory genes expression and HCC patient survival and identified four regulators that were remarkably associated with HCC patient prognosis. Additionally, an independent cohort from International Cancer Genome Consortium was studied to validate our discoveries and found to be consistent with those in the TCGA dataset. In terms of mechanism, gene set enrichment analysis linked these four genes with various physiological roles in cell division, the MYC pathway, protein metabolism, and mitosis. Kyoto Encyclopedia of Genes and Genomes analysis revealed that PI3K/Akt signaling pathway had potential relevance to m1A-related regulatory genes in HCC. These findings indicate that m1A-related regulatory genes may play crucial roles in regulating HCC progression and be exploited for diagnostic and prognostic purposes.

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Characterizing PD-L1/PD-1 expression in hepatocellular carcinoma and implications on postresection treatment response.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e15626 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e15626-e15626 ◽

Cited By ~ 1

Author(s):

Mark Farha ◽

Michael Green ◽

Issam El Naqa

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Cell ◽

Cox Regression ◽

Malignant Tumors ◽

Demographic Data ◽

Tnm Stage ◽

Recurrence Rates ◽

Time To Death ◽

Treatment Regimens ◽

Immune Score

e15626 Background: Despite recent progress in the treatment of liver cancer, its outcomes remain poor and recurrence rates are as high as 70% in 5 years. Here we seek to use PD-1 and PD-L1 expression to characterize the tumor immune microenvironment and determine whether the expression profile can be associated with response to specific treatments and be applied to personalize treatment regimens in the post-resection setting. Methods: Patients in the study had a mean age of 59, and the majority were caucasian (73%). Most were classified as Child-Pugh A (60%) and TNM stage 1-2 disease (63%). RNA Seq by Expectation Maximization (RSEM) values from the TCGA hepatocellular carcinoma (HCC) dataset for the PD-1 and PD-L1 genes were collected and normalized. RSEM values above the median were labeled “high”, while values below the median were labeled “low”. Corresponding clinical and demographic data were recorded. Survival analysis and multivariate Cox regression analyses were performed, and the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) scores were included to further characterize the tumor purity and the immune cell infiltration. Results: The median post-treatment survival of all patients was 32.4 months. Significant covariates impacting survival were age (HR = 1.05), AJCC TNM stage (HR = 1.61), and high PD-L1 expression (HR = 0.37). When stratified by ESTIMATE, the PD-1 high/PD-L1 high patient cohort had a mean immune score of 450, which was significantly higher than the other cohorts and the only positive score. Furthermore, when patients in this cohort were treated with chemotherapy, radiation, or sorafenib, their time-to-death was 20 months longer than patients from the same cohort treated with local embolization or ablation. Conclusions: We have provided data suggesting a survival advantage for patients with a positive ESTIMATE immune score and high PD-L1 and PD-1 expressions when treated with chemo, radiation, or sorafenib. Existing data suggests that immunotherapy can further synergize with these treatments in HCC and offer another promising approach to improve survival after resection for about 30% of HCC patients with this immune profile.

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Development and validation of prognostic nomograms in patients with hepatocellular carcinoma: a population-based study

Future Oncology ◽

10.2217/fon-2020-1065 ◽

2021 ◽

Author(s):

Youya Zang ◽

Peiyun Long ◽

Ming Wang ◽

Shan Huang ◽

Chuang Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Size ◽

Cox Regression ◽

Malignant Tumors ◽

Disease Free Survival ◽

Staging System ◽

Cox Regression Analysis ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Tumor Capsule

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The existing staging system has a limited budget capacity for HCC recurrence. The authors aimed to establish and verify two nomogram models to predict disease-free survival (DFS) and overall survival (OS) in patients with HCC. Methods: Patients diagnosed with HCC between August 2011 and March 2016 were recruited. Data were randomly divided into a training cohort and a validation cohort. Based on univariate and multivariate Cox regression analysis, independent risk factors for DFS and OS were identified, and two nomogram models were established to predict patient survival. Results: Sex, tumor size, Barcelona Clinic Liver Cancer (BCLC) stage, tumor capsule, macrovascular invasion, AST-to-platelet ratio index, AST-to-lymphocyte ratio index, neutrophil–lymphocyte ratio and alpha-fetoprotein (AFP) were used to build the nomogram for DFS, while age, tumor size, BCLC stage, tumor capsule, macrovascular invasion, systemic immune-inflammation index, AST, total bilirubin and AFP were used to build the nomogram for OS. Calibration curves showed good agreement between the nomogram prediction and actual observation. C-indices in both nomograms were significantly higher than BCLC. Conclusion: The two nomograms improved the accuracy of individualized prediction of DFS and OS, which may help doctors screen patients with a high risk of recurrence to formulate individualized treatment plans.

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Prognostic Value of an m6A RNA Methylation Regulator-Based Signature in Patients with Hepatocellular Carcinoma

BioMed Research International ◽

10.1155/2020/2053902 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Xiaomin Wu ◽

Xiaojing Zhang ◽

Leilei Tao ◽

Xichao Dai ◽

Ping Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Regression Analysis ◽

Cox Regression ◽

Malignant Tumors ◽

The Cancer Genome Atlas ◽

Prognostic Signature ◽

Cox Regression Analysis ◽

Rna Methylation ◽

M6a Rna Methylation ◽

Cluster 2

Purposes. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. Recent researches have demonstrated that m6A methylation regulators play a key role in various cancers, such as gastric cancer and colon adenocarcinoma. Several m6A methylation regulators are reported to predict the prognosis of HCC. Therefore, there is a need to further identify the predictive value of m6A methylation regulators in HCC. Methods. We utilized The Cancer Genome Atlas (TCGA) database to obtain the gene expression profile of m6A RNA methylation regulators and clinical information for patients with HCC. Besides, we identified two clusters of HCC with various clinical factors by consensus clustering analysis. Then the least absolute shrinkage and selection operator (LASSO) and the Cox regression analysis were applied to construct a prognostic signature. Results. Except for ZC3H13 and METTL14, a majority of the thirteen m6A RNA methylation regulators were significantly overexpressed in HCC specimens. HCC patients were classified into two groups (cluster 1 and cluster 2). The cluster 1 was with a significantly worse prognosis than cluster 2, and most of the 13 known m6A RNA methylation regulators were upregulated in cluster 1. Besides, we developed a prognostic signature consisting of YTHDF2, YTHDF1, METTL3, KIAA1429, and ZC3H13, which could successfully differentiate high-risk patients. More importantly, univariate and multivariate Cox regression analysis indicated that the signature-based risk score was an independent prognostic factor for patients with HCC. Conclusions. Our study showed these five m6A RNA methylation regulators can be used as practical and reliable prognostic tools of HCC, which might have potential value for therapeutic strategies.

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Effects of miRNA-140 on the Growth and Clinical Prognosis of SMMC-7721 Hepatocellular Carcinoma Cell Line

BioMed Research International ◽

10.1155/2021/6638915 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Cun-qing Kong ◽

Xing-cai Chen ◽

Guan-hua Qiu ◽

Jing-chen Liang ◽

Duo Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Regression Analysis ◽

Cox Regression ◽

Expression Level ◽

Migration And Invasion ◽

Clinical Prognosis ◽

Cox Regression Analysis ◽

Qrt Pcr ◽

Kaplan Meier ◽

Hcc Cells

Background. A growing number of studies have suggested that microRNAs exert an essential role in the development and occurrence of multiple tumours and act as crucial regulators in various biological processes. However, the expression and function of miRNA-140 in hepatocellular carcinoma (HCC) cells are not yet adequately identified and manifested. Methods. The expression of miRNA-140 was determined in HCC tissues and adjacent nontumour tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan–Meier survival analysis and Cox regression analysis were performed to explore the correlation between miRNA-140 expression level and the survival rate of patients with HCC. Additionally, overexpression experiments were conducted to investigate the biological role of miRNA-140 in HCC cells. Bioinformatics was used to predict the related target genes and pathways of miRNA-140. Results. QRT-PCR results signified that the expression level of miRNA-140 in HCC was lower than that of adjacent normal tissues ( P < 0.0001 ). Compared with the control group, the SMMC-7721 HCC cells in the miRNA-140 mimic group had a decrease in proliferation, migration, and invasion ( P < 0.05 ), whereas those in the miRNA-140 inhibitor group had an increase in proliferation, migration, and invasion ( P < 0.05 ). Cell cycle arrest occurred in the G0/1 phase. Prognosis analysis showed that the expression level of miRNA-140 was not related to the prognosis of HCC. Furthermore, the Kaplan–Meier test revealed that patients with lower miRNA-140 expression levels in liver cancer tissue had significantly shorter disease-free survival (DFS, P = 0.004 ) and overall survival (OS) times ( P = 0.010 ) after hepatectomy. Cox regression analysis further indicated that miRNA-140 was an independent risk factor that may affect the DFS ( P = 0.004 ) and OS times ( P = 0.014 ) of patients after hepatectomy. Our results suggested that miRNA-140 might be a crucial regulator involved in the HCC progression and is thus considered a potential prognostic biomarker and therapeutic target for HCC.

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Comprehensive Analysis of CDCAs Methylation and Immune Infiltrates in Hepatocellular Carcinoma

Frontiers in Oncology ◽

10.3389/fonc.2020.566183 ◽

2021 ◽

Vol 10 ◽

Author(s):

Yongkang Wang ◽

Yinfeng Yang ◽

Honglei Gao ◽

Ting Ouyang ◽

Luyao Zhang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Function ◽

Gene Networks ◽

Cox Regression ◽

Strong Association ◽

Cytotoxic Lymphocytes ◽

Bioinformatics Analyses ◽

Clinical Prognosis ◽

Cox Regression Analysis ◽

Essential Components

BackgroundAs essential components of cycle growth, the cell division cycle-associated family genes (CDCAs) have crucial roles in tumor development and progression, especially in hepatocellular carcinoma (HCC). However, due to the tumor heterogeneity of HCC, little is known about the methylation variability of CDCAs in mediating phenotypic changes (e.g., immune infiltrates) in HCC. Presently, we aim to comprehensively explore the expression and prognosis of CDCAs methylation with regard to immune infiltrates of HCC.MethodsWe first identified the correlating differentially expressed genes (co-DEGs) among 19 different types of cancer cohorts (a total of 7,783 patients) and then constructed the weighted gene co-expressed and co-methylated networks. Applying the clustering analysis, significant modules of DEGs including CDCAs were selected and their functional bioinformatics analyses were performed. Besides, using DiseaseMeth and TIMER, the correlation between the methylation levels of CDCAs and tumor immune infiltrates was also analyzed. In final, to assess the influence of CDCAs methylation on clinical prognosis, Kaplan-Meier and Cox regression analysis were carried out.ResultA total of 473 co-DEGs are successfully identified, while seven genes of CDCAs (CDCA1–3 and CDCA5–8) have significant over-expression in HCC. Co-expressed and co-methylated networks reveal the strong positive correlations in mRNA expression and methylation levels of CDCAs. Besides, the biological enrichment analysis of CDCAs demonstrates that they are significantly related to the immune function regulation of infiltrating immune cells in HCC. Also, the methylation analysis of CDCAs depicts the strong association with the tumor immunogenicity, i.e., low-methylation of CDCA1, CDCA2, and CDCA8 dramatically reduced the immune infiltrate levels of T cells and cytotoxic lymphocytes. Additionally, CDCA1–6 and CDCA8 with low-methylation levels significantly deteriorate the overall survival of patients in HCC.ConclusionsThe co-expressed and co-methylated gene networks of CDCAs show a powerful association with immune function regulation. And the methylation levels of CDCAs suggesting the prognostic value and infiltrating immune differences could be a novel and predictive biomarker for the response of immunotherapy.

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Role of Autophagy in the Prognosis of Combined Hepatocellular Carcinoma and Cholangiocarcinoma after Surgical Resection

10.21203/rs.3.rs-153575/v1 ◽

2021 ◽

Author(s):

Daw-Shyong Perng ◽

Hung-Yu Lin ◽

Paul Morgan ◽

Tsung-Chin Wu ◽

Chao-Ming Hung ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Disease Free Survival ◽

Clinicopathological Characteristics ◽

Clinical Prognosis ◽

Free Survival ◽

Cox Regression Analysis ◽

Tumor Tissues ◽

Related Proteins

Abstract Background: Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). Methods: We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. Results: We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7% and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68–26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01–0.34), p = 0.004, and 0.07 (0.01–0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85–922), p = 0.008, and 17.9 (1.05–306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2% and 74.6% in high LC3 expression patients and 0% and 0% in those with low LC3 expression. Conclusion: High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.

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