Guangjie Liu’s research while affiliated with Hebei Medical University and other places

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Publications (15)


Figure 1. Gene profiling in whole blood samples from patients with malignant nodules and benign nodules, and from nodule-free patients. (A) DEGs between malignant nodule blood samples and benign nodule blood samples [fdr <0.05 and log(fold-change) >0.05]. (B) DEGs between malignant nodule blood samples and benign nodule + no nodule blood samples [fdr <0.05 and log(fold-change) >0.05]. (C) The overlapped DEGs from malignant/benign nodules and malignant/(benign + no nodules) were obtained using VENNY. DEG, differentially expressed gene; fdr, false discovery rate; S100, S100 calcium binding protein P;
Figure 4. RNASE2 is a target gene of miR-185-5p. (A) A total of 10 overlapped miRNAs were found using VENNY. (B) Results of quantitative PCR showed that the transfections were successful. (C) Inhibition of RNASE2 by miR-185-5p mimic. (D) Construction of RNASE2-Wt and RNASE2-Mut. (E) Inhibition of RNASE2-Wt luciferase activity by miR-185-5p mimic. (F) Substantiation of the binding of RNASE2 to miR-185-5p by RIP. ** P<0.01 and *** P<0.001. miR, microRNA; NC, negative control; RNASE2, ribonuclease A family member 2; wt, wild-type; mut, mutant; RIP, RNA immunoprecipitation; Ago2, protein argonaute-2; IgG, immunoglobulin G.
RNA analysis of patients with benign and malignant pulmonary nodules
  • Article
  • Full-text available

January 2025

Oncology Letters

Guangjie Liu

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Qingyi Liu

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Yutong He

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[...]

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Fang Liu

Pulmonary nodules are the main manifestations of early lung cancer. Non-small cell lung cancer is the most common histological type of lung cancer, and the main histological classification of non-small cell lung cancer is lung adenocarcinoma. The present study aimed to analyze the differentially expressed genes between patients with benign and malignant pulmonary nodules, and to identify potential therapeutic targets for lung adenocarcinoma. Sequencing data for benign and malignant pulmonary nodule samples and samples with no nodules were obtained from the National Center for Biotechnology Information Gene Expression Omnibus GSE135304 dataset. Differential gene analysis showed that S100 calcium binding protein P (S100P), ribonuclease A family member 2 (RNASE2), cytochrome c oxidase subunit 7C and mast cell expressed membrane protein 1 (C19orf59) were significantly upregulated among the blood samples collected from patients with malignant pulmonary nodules. Results from Kaplan-Meier plotter datasets showed that S100P, RNASE2 and C19orf59 were associated with the prognosis of lung cancer. RNASE2 expression was positively associated with nodule size and negatively associated with lung cancer prognosis. Moreover, RNASE2 was highly expressed in lung adenocarcinoma tissues compared with that in normal tissues. CCK-8 and Transwell assays indicated that overexpressed RNASE2 promoted the proliferation, migration and invasion of lung adenocarcinoma cells. In lung adenocarcinoma cells, RNASE2 was identified as a downstream target of microRNA (miR)-185-5p and was regulated by it. Inhibited cell proliferation, migration and invasion were observed following overexpression of miR-185-5p. Overexpression of RNASE2 reversed the inhibitory effect of miR-185-5p overexpression. In conclusion, in blood samples from patients with malignant pulmonary nodules and lung adenocarcinoma tissues, RNASE2 was found to be upregulated. High RNASE2 expression was associated with poor overall survival. miR-185-5p inhibited the proliferation, migration and invasion of lung adenocarcinoma cells by downregulating RNASE2 expression. These findings have implications for guiding therapeutic strategies.

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CT data of the patient’s three pulmonary nodules.
Analysis of total exon results of three nodules. (A) Number of somatic mutations in three nodules. Colored circles represent different nodules, and the intersection is the common mutation of the three nodules. (B) The abscissa in the mutation spectrum histogram is the sample name, the ordinate is the proportion of each mutation type in the sample, and different colors represent different SNV types. (C) Proportion of each mutation feature in different samples. The abscissa represents the sample, and the ordinate represents the proportion of each mutation feature. (D) Cluster analysis of the mutation features of samples and 78 known mutation features. The darker the color is, the closer the cosine value is to 1, signifying that the higher the feature similarity is, the more likely it is the same feature.
When multiple primary lung cancers express the same rare mutation: a case report

The debate continues whether the expression of the same rare genetic mutation in multiple primary lung cancers suggests intrapulmonary metastasis or truly multiple primary lung cancers. We report a case of a 54-year-old female patient who presented with multiple nodules in the right lung discovered during a routine examination, persisting for six months. The patient had three central lesions in the right lung’s upper, middle, and lower lobes. She underwent thoracoscopic wedge resection, and the postoperative pathology reported two minimally invasive adenocarcinoma and one adenocarcinoma in situ. Interestingly, genetic testing for lung cancer-related driver genes revealed the presence of the rare RET mutation in all three nodules. This led us to speculate that these nodules might have the exact origin rather than being multiple primaries. To verify this hypothesis, we conducted further testing on these nodules, including whole-exome sequencing (The NGS data was generated from the Illumina sequencing platform by Novogene Co. Ltd, Beijing, China). The results indicated that although all three nodules expressed the RET mutation, there was significant heterogeneity in the gene mutations (differences in the number of cellular mutations, substitution composition levels, and clustering analysis of the three nodules). Thus, the patient was considered to have multiple primary lung cancers. In such cases, whole-exome sequencing can distinguish whether the nodules have the exact origin.


Selinexor as a Therapeutic Target: Advances in Non-small Cell and Small Cell Lung Cancer Treatment Strategies

October 2024

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4 Reads

Recent Patents on Anti-Cancer Drug Discovery

Selinexor treats lung cancer, particularly non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). This review summarizes the prevalence and types of lung cancer and emphasizes the challenges associated with current treatments like resistance and limited effectiveness. Selinexor is a selective inhibitor of nuclear export (SINE) that has emerged as a potential therapy that targets the nuclear export of tumor suppressor proteins. The mechanisms of selinexor, its potential in combination therapies, and challenges like side effects and drug resistance are explained in this review. Key findings highlight the effectiveness of selinexor in preclinical studies, particularly against KRAS-mutant NSCLC and in combination with chemotherapy for SCLC. The review concludes with a discussion of future directions and underscores the potential of selinexor to improve the treatment strategies for lung cancer.


Figure 2
Comparison of tumor biomarkers between different groups
Comparison of cytokines levels in different groups
A high-performance metabolomic diagnostic panel for early-stage non-small cell lung cancer detection based on UPLC‒MS/MS

May 2024

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16 Reads

Lung cancer is the most common cancer in the world and has a consistently high mortality rate, with the majority of patients being diagnosed at an advanced stage. This study aimed to identify potential biomarkers through metabolomics to provide clues for the diagnosis and treatment of early-stage non-small cell lung cancer (NSCLC). We enrolled two prospective cohorts with a total of 180 patients (115 patients with I-II a NSCLC and 65 healthy controls) and tested serum samples for tumour markers, cytokines, and 306 metabolites by ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UPLC‒MS/MS). In both the discovery and validation cohorts, there were 57 differentially abundant metabolites in the serum between patients with early-stage NSCLC and healthy controls, which were concentrated in the fatty acid metabolic pathway and amino acid metabolic pathway. Finally, three metabolites with significant differences were screened as isoleucine, 5Z-dodecenoic acid and 9E-tetradecenoic acid. The AUC of centralized combined diagnosis reached 0.95. This study provides new evidence that abnormalities in valine, leucine, and isoleucine metabolism and dysregulation of fatty acid synthesis may play important roles in the development of NSCLC.


Value of exhaled hydrogen sulfide in early diagnosis of esophagogastric junction adenocarcinoma

May 2024

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12 Reads

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1 Citation

Oncology Letters

Esophagogastric junction adenocarcinoma (EJA) has increased in recent years, and it exhibits a poor prognosis and a short survival period for patients. Hydrogen sulfide (H2S) plays an important role in the pathogenesis of cancer and has been studied as a diagnostic factor in some tumor diseases. However, few studies have explored the diagnostic value of H2S for EJA. In the present study, a total of 56 patients with early-stage EJA were enrolled while 57 healthy individuals were selected as the healthy control group. Clinical features were recorded, and exhaled H2S and blood samples were collected from both groups. Exhaled H2S and serum interleukin-8 (IL-8) expression levels were detected in both groups. The correlation between exhaled H2S and serum IL-8 levels was analyzed using Pearson's correlation method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of exhaled H2S combined with IL-8 detection in EJA. The results showed that patients with EJA exhaled more H2S than healthy individuals. In addition, exhaled H2S was positively correlated with increased IL-8 expression. The ROC curve revealed that the exhaled H2S test had an acceptable diagnostic effect and could be used to diagnose EJA. The increase in H2S exhaled by patients with EJA indicated that H2S may be related to the occurrence and development of EJA; however, the in vivo mechanism needs to be further explored. Collectively, it was determined in the present study that exhaled H2S was significantly higher in patients with early-stage EJA than in healthy controls and combined diagnosis with patient serum IL-8 could improve diagnostic accuracy, which has potential diagnostic value for early diagnosis and screening of EJA.


Identification of INHBA as a potential biomarker for gastric cancer through a comprehensive analysis

August 2023

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45 Reads

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9 Citations

Inhibin subunit beta A (INHBA) is a member of the transforming growth factor-beta (TGF-β) superfamily that plays a fundamental role in various cancers. However, a systematic analysis of the exact role of INHBA in patients with gastric cancer (GC) has not yet been conducted. We evaluated the expression levels of INHBA and the correlation between INHBA and GC prognosis in GC. The relationship between INHBA expression, immune infiltration levels, and type markers of immune cells in GC was also explored. In addition, we studied INHBA mutations, promoter methylation, and functional enrichment analysis. Besides, high expression levels of INHBA in GC were significantly related to unfavorable prognosis. INHBA was negatively correlated with B cell infiltration, but positively correlated with macrophage and most anticancer immunity steps. INHBA expression was positively correlated with the type markers of CD8+ T cells, neutrophils, macrophages, and dendritic cells. INHBA has a weak significant methylation level change between tumor and normal tissues and mainly enriched in cancer-related signaling pathways. The present study implies that INHBA may serve as a potential biomarker for predicting the prognosis of patients with GC. INHBA is a promising predictor of immunotherapy response, with higher levels of INHBA indicating greater sensitivity.


Adjuvant chemotherapy can benefit the survival of stage I lung adenocarcinoma patients with tumour spread through air spaces after resection: Propensity-score matched analysis

August 2022

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23 Reads

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5 Citations

Background It is still unclear whether stage I lung adenocarcinoma patients with tumour spread through air spaces (STAS) can benefit from postoperative adjuvant chemotherapy (ACT) after lobectomy. This study investigated the effect of ACT on the postoperative survival of patients with stage I (STAS⁺) lung adenocarcinoma. Methods We retrospectively analysed the clinical data of stage I (STAS⁺) invasive lung adenocarcinoma patients who underwent lobectomy in the Department of Thoracic Surgery of our hospital from January 1, 2013 to January 1, 2016. Propensity score matching (PSM) was performed to group patients to investigate whether ACT could lead to better prognosis of patients. Results A total of 593 patients with stage I (STAS⁺) lung adenocarcinoma were enrolled. The study after PSM included 406 patients. Kaplan–Meier survival analysis showed the experimental group had a better 3-year recurrence-free survival (RFS) rate (p = 0.037) and the 5-year RFS rate (p = 0.022) than the control group. It also had higher 5-year overall survival (p = 0.017). The multivariate analysis by Cox proportional hazard regression model showed that stage I STAS⁺ lung adenocarcinoma patients with lymphatic vessel invasion (HR: 1.711, 95% CI: 1.052-2.784; p = 0.045), vascular invasion (HR: 5.014, 95% CI: 3.154-7.969; p < 0.001), and visceral pleural invasion (HR: 2.086, 95% CI: 1.162-3.743; p = 0.014), and without ACT (HR: 1.675, 95% CI: 1.043-2.689; p = 0.033) had a significant survival disadvantage. Conclusion ACT can boost the postoperative survival of patients with stage I (STAS⁺) lung adenocarcinoma.


Flow chat of SMGGN patient enrollment and examination.
The distribution of EGFR mutations in 87 patients.
Pathological and molecular-biological characteristics of 87 patients. Variable/characteristic Result/No. of patients (%)
Application Value of PET/CT and MRI in the Diagnosis and Treatment of Patients With Synchronous Multiple Pulmonary Ground-Glass Nodules

February 2022

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27 Reads

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1 Citation

Background Synchronous multiple ground-glass nodules (SMGGNs) in synchronous multiple lung cancers are associated with specific imaging findings. It is difficult to distinguish whether multiple nodules are primary tumors or metastatic lesions in the lungs. The need for PET/CT and contrast-enhanced brain MRI for these patients remains unclear. This study investigated the necessity of these two imaging examinations for SMGGN patients by means of retrospective analysis. Methods SMGGN patients who were diagnosed and treated in our hospital from October 2017 to May 2020 and underwent whole-body PET/CT(Cranial excepted) and/or contrast-enhanced brain MRI+DWI were enrolled in this study. We analyzed the imaging and clinical characteristics of these patients to evaluate SMGGN patients’ need to undergo whole-body PET/CT and brain MRI examination. Results A total of 87 SMGGN patients were enrolled. 51 patients underwent whole-body PET/CT examinations and did not show signs of primary tumors in other organs, metastatic foci in other organs, or metastasis to surrounding lymph nodes. 87 patients underwent whole-brain MRI, which did not reveal brain metastases but did detect an old cerebral infarction in 23 patients and a new cerebral infarction in one patient. 87 patients underwent surgical treatment in which 219 nodules were removed. All nodules were diagnosed as adenocarcinoma or atypical adenomatous hyperplasia. No lymph node metastasis was noted. Conclusion For SMGGN patients, PET/CT and enhanced cranial MRI are unnecessary for SMGGNs patients, but from the perspective of perioperative patient safety, preoperative MRI+DWI examination is recommended for SMGGNs patients.


Regulatory Mechanism and Experimental Verification of Patchouli Alcohol on Gastric Cancer Cell Based on Network Pharmacology

September 2021

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54 Reads

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13 Citations

Background Pogostemon cablin is a traditional Chinese medicine (TCM) that is frequently used to treat various gastrointestinal diseases. Patchouli alcohol (PA), a compound extracted from the Pogostemon cablin, has been shown to have anti-tumor efficacy in human colorectal cancer. However, the mechanism of PA’s anticancer effect on gastric cancer (GC) remains unknown. Methods We used the public database to obtain the potential targets of PA and genes related to GC. Bioinformatic analyses, such as the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and protein-protein interactions (PPI), were used for analyzing the potential signal pathways and targets. Cell experiments were also conducted to further explain the impact and molecular mechanism of PA on GC, as well as to confirm the findings of network pharmacology. Results Using network pharmacological analysis, 161 possible targets were identified for the treatment of GC. Network analysis and functional enrichment analysis show that PA produced a marked effect in the treatment of GC through multi-targets and multi-pathways, especially the MAPK and PI3K/AKT signal pathways. In addition, PA showed the inhibition of GC cell proliferation, migration and invasion in cell experiments. According to our findings, PA could also cause G0/G1 phase arrest and apoptosis in GC cells. Conclusion Using network pharmacology, we aim to uncover the possible molecular mechanism of PA on GC treatment in this research. Cell experiments were also conducted to confirm the therapeutic effect of PA on GC.


Figure 1. Identification of differentially expressed genes (DEGs) and differentially methylated genes (DMGs) in colon adenocarcinoma (COAD). (A) Flowchart showing overall design and analytic procedure of this study. (B) Overlapping of DEGs from TCGA and GSE39582. (C) Overlapping of DMGs from TCGA and GSE48684. (D) Identification of aberrantly methylated DEGs.
Figure 2. Correlation between the expression value and methylation value of the methylation-driven genes (MDGs) in colon adenocarcinoma (COAD) tissues.
Figure 7. Representative enriched pathways in four candidate genes from gene set enrichment analysis (GSEA) software.
Six MDGs associated with overall survival (OS) of colon adenocarcinoma (COAD) patients.
Clinical information of the study patients.
Development and Validation of a Risk Prediction Model and Nomogram for Colon Adenocarcinoma Based on Methylation-driven Genes

June 2021

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20 Reads

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9 Citations

Aging

Evidence suggests that abnormal DNA methylation patterns play a crucial role in the etiology and pathogenesis of colon adenocarcinoma (COAD). In this study, we identified a total of 97 methylation-driven genes (MDGs) through a comprehensive analysis of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate Cox regression analysis identified four MDGs (CBLN2, RBM47, SLCO4C1, and TMEM220) associated with overall survival (OS) in COAD patients. A risk prediction model was then developed based on these four MDGs to predict the prognosis of COAD patients. We also created a nomogram that incorporated risk scores, age, and TNM stage to promote a personalized prediction of OS in COAD patients. Compared with the traditional TNM staging system, our new nomogram was better at predicting the OS of COAD patients. In cell experiments, we confirmed that the mRNA expression levels of CLBN2 and TMEM220 were regulated by the methylation of their promoter regions. Moreover, immunohistochemistry showed that CBLN2 and TMEM220 were potential prognostic biomarkers for COAD patients. In summary, we have established a risk prediction model and nomogram that might be effectively utilized to promote the prediction of OS in COAD patients.


Citations (6)


... Results suggested INHBA modulates cell proliferation as well as migration; however, the mechanism behind this is still unclear 21 . A comprehensive study also reported INHBA as a promising predictor of immunotherapy response as they evaluated the expression of INHBA and the correlation between INHBA and GC prognosis and revealed that INHBA expression was positively correlated with the type markers of CD8 + T cells, neutrophils, macrophages, and dendritic cell 22 . A recent study in colorectal cancer suggested an interplay of HNF1A-AS1/ miR-214/ INHBA axis regulation in TGF β / SMAD signaling based on their preliminary results, where they showed the expression of HNF1A-AS1 was negatively correlated with hsa-miR-214 and hsa-miR-214 targets INHBA, and expression INHBA and HNF1A-AS1 were found to be increased in colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ) 23 . ...

Reference:

Comprehensive analysis of inhibin-β A as a potential biomarker for gastrointestinal tract cancers through bioinformatics approaches
Identification of INHBA as a potential biomarker for gastric cancer through a comprehensive analysis

... Although STAS is considered an independent high-risk factor for LUAD, its impact on the need for adjuvant therapy in surgically treated early-stage LUAD patients remains uncertain. Adjuvant therapy may be beneficial for Stage IB STAS-positive patients, whereas the benefits of adjuvant therapy for Stage IA patients are controversial [11][12][13] . Only moderate interobserver agreement exists among physicians in STAS diagnosis for LUAD patients who underwent surgery 14 . ...

Adjuvant chemotherapy can benefit the survival of stage I lung adenocarcinoma patients with tumour spread through air spaces after resection: Propensity-score matched analysis

... In contrast, GGNs in the contralateral lung were more commonly detected in patients with neoplastic GGNs. It indicates that scattered GGNs in bilateral lungs had a higher possibility of neoplasm, 26,27 and at the level of genetic research, multiple GGNs are often multifocal and independent cancers. 28 Regarding the efficacy of different indicators or parameters in the differential diagnosis of non-neoplastic GGNs, the AUC of model based solely on CT features of target GGNs is higher than that only based on intrapulmonary concomitant lesions, but lower than that based on the combination of CT features of target GGNs and intrapulmonary concomitant lesions. ...

Application Value of PET/CT and MRI in the Diagnosis and Treatment of Patients With Synchronous Multiple Pulmonary Ground-Glass Nodules

... 2,3 At present, patchouli volatile oil and its component (patchouli alcohol) played an adjuvant role in the treatment of SARS-CoV-2 infection, providing a potential choice for subsequent drug development. 4 The phytochemistry of patchouli has been extensively studied, and its components were mainly volatile components (sesquiterpenoids) and non-volatile components including other terpenes, pyrones, flavonoids, [5][6][7] Pharmacological research objects of patchouli mainly focus on volatile oil 8-10 and its single components patchouli alcohol 11,12 and pogostone, 13,14 which had the efficacy of regulating gastrointestinal activity, [15][16][17][18] inhibiting pathogenic microorganisms, [19][20][21] anti-inflammatory activity, 22,23 anti-tumor effect, 24,25 insecticidal activity, 26 etc. Terpenes, flavonoids and phenylpropanes accounted for 40%, 20% and 10% of the patchouli total components; 27 while most of the previous studies just focused on the volatile oil components of terpenes and paid little attention to non-volatile ingredients. ...

Regulatory Mechanism and Experimental Verification of Patchouli Alcohol on Gastric Cancer Cell Based on Network Pharmacology

... Prior studies have confirmed that SLCO4C1 has relatively low expression in prostate cancer, 47 acting as a protective gene for patient prognosis in colon adenocarcinoma. 48 Another Figure 7. The absence of MBNL1 or QKI promotes tumor growth of ESCC in xenograft models. ...

Development and Validation of a Risk Prediction Model and Nomogram for Colon Adenocarcinoma Based on Methylation-driven Genes

Aging

... CTCs, direct indicators of tumor presence, reveal a correlation between specific gene mutations and cancer metabolites, promising avenues for early diagnostic markers [52]. However, the challenge lies in their rarity and the technical hurdles in their isolation and analysis [49]. ...

Circulating Tumor Cell and Metabolites as Novel Biomarkers for Early-Stage Lung Cancer Diagnosis