Publications by authors named "Guo-Ming Shi"

Article Synopsis
  • Single-cell technology offers a more comprehensive view of tumors by analyzing both tumor cells and their surrounding microenvironments, potentially improving diagnosis compared to traditional methods that focus solely on pathology.
  • Despite its advantages, single-cell RNA sequencing (scRNA-seq) faces significant issues, including complex data structures and low signal clarity, which hinder its diagnostic use.
  • The authors introduce a graph neural network framework designed for diagnosing primary liver tumors by leveraging scRNA-seq data and intercellular communication networks, demonstrating accurate differentiation between malignant and benign tumors and validating their findings with public datasets.
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  • Intratumoral immune status plays a crucial role in how patients with intrahepatic cholangiocarcinoma respond to therapy, especially with a combination of gemcitabine, oxaliplatin, lenvatinib, and anti-PD1 antibody.
  • High levels of certain CD8 T-cell markers (GZMB and proliferating CD8) and low levels of Macro CD5L predict better therapeutic responses, while shifts in T-cell markers indicate varying response levels.
  • The study also suggests that using anti-CTLA4 antibody can counteract therapy resistance caused by immune exhaustion, paving the way for more effective cancer treatments based on immune profiling.
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  • Intrahepatic cholangiocarcinoma (iCCA) can arise from various parts of the intrahepatic biliary tree and is classified into subtypes based on their origins, such as large duct, small duct, and cholangiolocarcinoma.
  • Diagnosing these subtypes is challenging due to differences in cell structure, growth patterns, and other pathological features.
  • An expert consensus has proposed nine recommendations to standardize the diagnosis of these iCCA subtypes, referring mainly to the latest World Health Organization classification.
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  • The tumor microenvironment is complex and includes tumor-associated macrophages (TAMs), which can be influenced by tumor cells to create an environment that supports tumor growth.
  • This study found that liver cancer (HCC) cells cause macrophages to change into a M2-like phenotype, which is associated with promoting cancer, and that this change is linked to the role of autophagy in macrophage behavior.
  • Inhibiting autophagy in macrophages leads to M2 polarization through a specific mechanism involving the NF-κB pathway, highlighting a potential target for cancer treatment by disrupting this polarization process.
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Background: The dysregulation of exosomal microRNAs plays an important role in the progression of hepatocarcinogenesis. In this study, we investigated the therapeutic potential of synthetic exosomal miR-26a against HCC cells and explored the feasibility of tumor-derived exosomes as drug delivery vehicles.

Methods: Proliferation and migration assays were performed to examine the effects of miR-26a on HCC in vitro.

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Article Synopsis
  • Evading the immune system is a key feature of cancer, particularly in the development of hepatocellular carcinoma (HCC), and understanding this process is crucial for finding new treatments.
  • The study identifies miR-93-5p as a significant oncogene involved in HCC progression and immune evasion, as it disrupts tumor suppressors and affects immune cell function.
  • Blocking GAL-9, which is linked to high levels of miR-93-5p, shows promise as a new immunotherapeutic strategy to counteract HCC and improve patient outcomes.
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  • The study investigates the role of autophagy in macrophages within the tumor microenvironment of hepatocellular carcinoma (HCC), finding reduced autophagy linked to worse patient outcomes and increased metastasis.
  • Researchers identified that HCC triggers decreased autophagy in macrophages by activating mTOR, which in turn promotes cancer progression through mechanisms involving the NLRP3 inflammasome and IL-1β release.
  • Targeting the signaling pathways related to IL-1β showed potential as a therapeutic strategy, indicating that disrupting the feedback loop between autophagy inhibition and macrophage recruitment could help treat HCC more effectively.
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  • Advanced intrahepatic cholangiocarcinoma (ICC) has poor outcomes, but a new combination therapy of toripalimab, lenvatinib, and GEMOX shows promise as a first-line treatment.
  • In a study of 30 patients, the therapy resulted in an 80% objective response rate, with most experiencing either partial or complete responses, and an overall disease control rate of 93.3%.
  • While manageable adverse events occurred in over half of the patients, including neutropenia and leukocytopenia, the overall survival and progression-free survival were encouraging, prompting further validation in a larger clinical trial.
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  • * Lower levels of 5-hydroxymethylcytosine (5-hmC) in HCC tissues are associated with worse cancer characteristics and resistance to chemotherapy after liver transplantation.
  • * The enzyme TET2 regulates 5-hmC levels, and its reduction leads to chemotherapy resistance via inhibition of PCAF and hyperactivation of AKT signaling, making it a potential target for improving treatment outcomes.
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Background: Perineural invasion (PNI) is associated with metastasis in malignancies, including intrahepatic cholangiocarcinoma (ICC), and is correlated with poor prognosis.

Methods: The study included three large cohorts: ZS-ICC and TMA cohorts from our team, MSK cohort from a public database, and a small cohort named cohort 4. Prognostic implications of PNI were investigated in MSK cohort and TMA cohort.

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Background: Avatrombopag has been approved in patients who have severe thrombocytopenia (<50 × 10/L) and chronic liver disease (CLD) while receiving invasive procedures. The real-world application and effectiveness of avatrombopag in the subgroup patients with liver cancer remain unknown.

Methods: Liver cancer patients (including primary liver cancer and colorectal cancer liver metastasis) who had severe thrombocytopenia and received avatrombopag were retrospectively enrolled.

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Objective: This study evaluated the antitumor activity and safety of pemigatinib in previously treated Chinese patients with advanced cholangiocarcinoma and fibroblast growth factor receptor 2 (FGFR2) fusions or rearrangements.

Background: Pemigatinib provided clinical benefits for previously treated patients with cholangiocarcinoma carrying FGFR2 fusions or rearrangements and was approved for this indication in multiple countries.

Methods: In this ongoing, multicenter, single-arm, phase II study, adult patients with locally advanced or metastatic cholangiocarcinoma carrying centrally confirmed FGFR2 fusions or rearrangements who had progressed on ≥1 systemic therapy received 13.

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Background: Laparoscopic liver resection (LLR) has now been established as a safe and minimally invasive technique that is deemed feasible for treating hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). However, the role of LLR in treating combined hepatocellular-cholangiocarcinoma (cHCC-CC) patients has been rarely reported. This study aimed to assess the efficacy of LLR when compared with open liver resection (OLR) procedure for patients with cHCC-CC.

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Background: Kinase suppressor of Ras 2 (KSR2) is a regulator of MAPK signaling that is overactivated in most hepatocellular carcinoma (HCC). We sought to determine the role of KSR2 in HCC pathogenesis.

Methods: We tested the level of KSR2 in HCC tissues and cell lines by tissue microarray, qPCR, and western blotting.

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Background: While the correlation between PD-L1 expression and KRAS mutation has been previously reported in other solid tumors such as non-small cell lung cancer (NSCLC), whether PD-L1 can be modulated by ERK signaling downstream of KRAS in intrahepatic cholangiocarcinoma (iCCA) and the underlying molecular regulatory mechanism remain unclear.

Methods: The expression of ERK, p-ERK, PD-L1 and autophagy markers following KRAS knockdown or Ras/Raf/MEK/ERK signaling inhibitors treatment was examined in two human iCCA cell lines (HuCCT1 and RBE) using western blotting and immunofluorescence. Both pharmacological autophagy inhibitors and short-interfering RNA against ATG7 were applied to inhibit autophagy.

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Background: Major hepatectomy is associated with high incidence of post-hepatectomy liver failure (PHLF). This study aimed to evaluate the effect of future remnant liver volume combined with liver function tests on predicting PHLF.

Methods: Patients who underwent major hepatectomy from April 2009 to May 2017 were enrolled in the training cohort.

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Background: Immune checkpoint blockade resistance narrows the efficacy of cancer immunotherapies, but the underlying mechanism remains elusive. Delineating the inherent mechanisms of anti-PD1 resistance is important to improve outcome of patients with advanced HCC.

Method: The level of cricTMEM181 was measured in HCC patients with anti-PD1 therapy by RNA sequencing and then confirmed by qPCR and Sanger sequencing.

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Intrahepatic cholangiocarcinoma (ICC) is highly invasive and carries high mortality due to limited therapeutic strategies. In other solid tumors, immune checkpoint inhibitors (ICIs) target cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD1), and the PD1 ligand PD-L1 has revolutionized treatment and improved outcomes. However, the relationship and clinical significance of CTLA-4 and PD-L1 expression in ICC remains to be addressed.

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Background: Remnant liver hypoperfusion is frequently observed after hepatectomy, and associated with a higher risk of postoperative complications and poorer survival. However, the development of remnant liver hypoperfusion was not fully understood.

Methods: We retrospectively analyzed patients who received hepatectomy and took contrast-enhanced computed tomography (CT) scans before, 1-week (POW1) and 4-week (POW4) after resection in our department from June 2017 to July 2019.

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Background: Cirrhosis is a recognized risk factor for developing hepatocellular carcinoma (HCC). Few studies have reported the expression profile of circRNAs in HCC samples compared to paratumour dysplastic nodule (DN) samples.

Methods: The Arraystar Human circRNA Array combined with laser capture microdissection (LCM) was used to analyse the expression profile of circRNAs in HCC samples compared to paratumour DN samples.

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Background: Survival after resection of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) still remains poor. Apatinib, a vascular endothelial cell growth factor receptor 2 inhibitor, has been shown to be safe and effective in patients with advanced HCC, so in the present study its efficacy and safety in the adjuvant setting was explored.

Methods: In this single-center, open-label phase II trial, the patients received apatinib (500 mg/day) until they experienced disease recurrence or intolerable toxicity.

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Background: The incidence of combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma (cHCC-ICC) is relatively low, and the knowledge about the prognosis of cHCC-ICC remains obscure. In the study, we aimed to screen existing primary liver cancer staging systems and shed light on the prognosis and risk factors for cHCC-ICC.

Methods: We retrospectively reviewed 206 cHCC-ICC patients who received curative surgical resection from April 1999 to March 2017.

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Article Synopsis
  • Natural killer (NK) cells are important for fighting tumors, but their dysfunction is observed in hepatocellular carcinoma (HCC), which is not fully understood.
  • The study found that the circular RNA circUHRF1 is expressed at higher levels in HCC tissues and correlates with poor prognosis and NK cell dysfunction by reducing their ability to secrete key immune signals.
  • CircUHRF1 also contributes to NK cell dysfunction by promoting TIM-3 expression through miR-449c-5p degradation, potentially leading to resistance against immunotherapy in HCC patients.
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