Development of a prognostic model for anoikis and identifies hub genes in hepatocellular carcinoma

Zhong, Zhiwei; Xie, Fuchun; Yin, Jiajun; Zhao, Hua; Zhou, Yuehan; Guo, Kun; Li, Rongkuan; Wang, Qimin; Tang, Bo

doi:10.1038/s41598-023-41139-9

Cited by 3 publications

(3 citation statements)

References 87 publications

(81 reference statements)

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“…Skp2 plays multiple roles in malignant tumors ( 38 ). SKP2 is over-expressed in HCC tissues, and its over-expression is associated with poor prognosis ( 39 ). Lung cancer is a typical type of cancer resistant to chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Prognosis comparison between hepatocellular carcinoma patients with microvascular invasion who received hepatectomy alone and those who underwent early PA-TACE: a retrospective cohort study

Ma,

Zhou,

Huang

et al. 2024

J Gastrointest Oncol

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Background Postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) can achieve longer overall survival (OS) and disease-free survival (DFS) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). We investigated whether this treatment strategy could benefit these patients by mediating the dysfunctional immunological status. Therefore, a retrospective cohort study was conducted to investigate the effect of early PA-TACE in HCC patients with MVI by measuring the levels of T helper cell 17 (Th17) and regulatory T cell (Treg). Methods This study retrospectively included 472 patients with HCC undergoing hepatectomy between December 2015 and December 2018, and 115 patients with MVI confirmed by postoperative pathology were enrolled and divided into two groups of TACE group and non-TACE group according to whether TACE was performed. HCC patients with MVI. The proportion of Treg and Th17 cells in peripheral blood was measured one day before and four weeks after TACE. All patients in the two groups were followed up until death or until the study ended in December 2023. The rates of OS and progression-free survival (PFS) in patients with MVI were compared between those who received hepatectomy alone and those who underwent early PA-TACE. Results Among 115 HCC patients with MVI from 472 patients, the study enrolled 51 patients with PA-TACE into the TACE group and 42 patients without TACE into the non-TACE group. There were no statistical differences in baseline data between the two groups (all P>0.05). The frequency of Treg among CD4+ T cells in HCC patients with PA-TACE was significantly lower than baseline (7.34%±3.61% vs . 5.82%±2.76%, P<0.001), and the frequency of Th17 among CD4 + T cells in these patients was significantly higher than baseline (0.49%±0.28% vs . 0.50%±0.25%, P<0.001). Among all the patients, the median OS was 61.8 months. The OS rate and PFS rate at 12, 36, and 60 months in the TACE group were significantly higher than those in the non-TACE group (all P<0.05). Conclusions PA-TACE may have roles in improving survival outcomes, and restoring immune homeostasis in HCC patients with MVI after hepatectomy.

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Section: Discussionmentioning

confidence: 99%

Prognosis comparison between hepatocellular carcinoma patients with microvascular invasion who received hepatectomy alone and those who underwent early PA-TACE: a retrospective cohort study

Ma,

Zhou,

Huang

et al. 2024

J Gastrointest Oncol

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“…Recently, Zhong et al established a risk score model from the perspective of anoikis, which was externally verified by ICGC cohort but not internally verified in TCGA cohort. 47 The prognosis model we established was not only validated internally, but also externally by multiple datasets.…”

Section: Discussionmentioning

confidence: 99%

The Characteristics of Transcription Factors Regulating T Cell Exhaustion Were Analyzed to Predict the Prognosis and Therapeutic Effect in Patients with HCC

Li,

Zhou,

et al. 2023

IJGM

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Purpose Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer-related deaths, posing a significant threat to people in diverse regions. T-cell exhaustion (Tex) can hinder the efficacy of immunotherapy in patients with HCC, and the transcription factors that regulate Tex in HCC have not yet been fully elucidated. Patients and Methods We used the single sample gene set enrichment analysis (ssGSEA) method to define the transcription factor pathway that regulates Tex and employed LASSO regression analysis to establish Tex related genes (TEXRS). To predict differences in immunotherapy efficacy between the two groups, we used the immunophenotype score and submap algorithm. RT-qPCR was used to detect the expression levels of the model genes in 21 pairs of HCC tissues. Finally, we assessed the cell communication strength and identified ligand receptors using the “CellChat” R package. Results Nine Tex transcription factors were identified as regulators of the HCC immune microenvironment, with Tex scores affecting patient survival. Patients with a high Tex Risk Score (TEXRS) had significantly worse overall survival compared to patients with low TEXRS. After adjusting for confounding factors, TEXRS remained an independent prognostic factor. Importantly, TEXRS performed well in multiple independent external validation cohorts. Various algorithms have shown that patients in the low-TEXRS group might benefit more from immunotherapy. Finally, RT-qPCR analysis of 21 HCC samples showed that C7, CD5L, and SDS were significantly downregulated in HCC tissues, consistent with the bioinformatics analysis results. Conclusion TEXRS proved to be a valuable predictor of immunotherapy and transcatheter arterial chemoembolization efficacy in patients with HCC. This holds promise for enhancing the prognosis and treatment outcomes of patients with HCC.

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“…10,11,34,35 KDM5B and SKP2 are involved in many biological functions, including gene regulation, cell development, and proliferation. 15,[36][37][38][39][40] In addition, elevation of KDM5B and SKP2 promotes tumorigenic properties and cancer metastasis in several human cancers, including prostate, breast, and liver cancer, 13,15,41,42 as well as drug resistance of cancer cells. [43][44][45][46] Nevertheless, the relationship between KDM5B and SKP2 in PCa was elusive, and that information is important for the development of effective drugs for PCa patients who failed ADT.…”

Section: Combination Inhibition Of Skp2 and Kdm5b Abrogates Akt Signa...mentioning

confidence: 99%

Co‐targeting SKP2 and KDM5B inhibits prostate cancer progression by abrogating AKT signaling with induction of senescence and apoptosis

Brown,

Kanagasabai,

et al. 2024

The Prostate

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BackgroundProstate cancer (PCa) is the second‐leading cause of cancer mortalities in the United States and is the most commonly diagnosed malignancy in men. While androgen deprivation therapy (ADT) is the first‐line treatment option to initial responses, most PCa patients invariably develop castration‐resistant PCa (CRPC). Therefore, novel and effective treatment strategies are needed. The goal of this study was to evaluate the anticancer effects of the combination of two small molecule inhibitors, SZL‐P1‐41 (SKP2 inhibitor) and PBIT (KDM5B inhibitor), on PCa suppression and to delineate the underlying molecular mechanisms.MethodsHuman CRPC cell lines, C4‐2B and PC3 cells, were treated with small molecular inhibitors alone or in combination, to assess effects on cell proliferation, migration, senescence, and apoptosis.ResultsSKP2 and KDM5B showed an inverse regulation at the translational level in PCa cells. Cells deficient in SKP2 showed an increase in KDM5B protein level, compared to that in cells expressing SKP2. By contrast, cells deficient in KDM5B showed an increase in SKP2 protein level, compared to that in cells with KDM5B intact. The stability of SKP2 protein was prolonged in KDM5B depleted cells as measured by cycloheximide chase assay. Cells deficient in KDM5B were more vulnerable to SKP2 inhibition, showing a twofold greater reduction in proliferation compared to cells with KDM5B intact (p < 0.05). More importantly, combined inhibition of KDM5B and SKP2 significantly decreased proliferation and migration of PCa cells as compared to untreated controls (p < 0.005). Mechanistically, combined inhibition of KDM5B and SKP2 in PCa cells abrogated AKT activation, resulting in an induction of both cellular senescence and apoptosis, which was measured via Western blot analysis and senescence‐associated β‐galactosidase (SA‐β‐Gal) staining.ConclusionsCombined inhibition of KDM5B and SKP2 was more effective at inhibiting proliferation and migration of CRPC cells, and this regimen would be an ideal therapeutic approach of controlling CRPC malignancy.

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Development of a prognostic model for anoikis and identifies hub genes in hepatocellular carcinoma

Cited by 3 publications

References 87 publications

Prognosis comparison between hepatocellular carcinoma patients with microvascular invasion who received hepatectomy alone and those who underwent early PA-TACE: a retrospective cohort study

Prognosis comparison between hepatocellular carcinoma patients with microvascular invasion who received hepatectomy alone and those who underwent early PA-TACE: a retrospective cohort study

The Characteristics of Transcription Factors Regulating T Cell Exhaustion Were Analyzed to Predict the Prognosis and Therapeutic Effect in Patients with HCC

Co‐targeting SKP2 and KDM5B inhibits prostate cancer progression by abrogating AKT signaling with induction of senescence and apoptosis

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