Publications by authors named "Guangsheng Zhu"

8 Publications

  • Page 1 of 1

Prognostic value of ferroptosis-related genes in patients with lung adenocarcinoma.

Thorac Cancer 2021 Jun 12;12(12):1890-1899. Epub 2021 May 12.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Background: The prevalence of lung adenocarcinomas (LUADs) has dramatically increased in recent decades. Ferroptosis is a process of iron-dependent regulatory cell death. It is still unclear whether the expression of ferroptosis-related genes (FRGs) is involved in the pathogenesis and survival of patients with LUAD.

Methods: We retrieved LUAD data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and used LASSO Cox regression analysis to select the gene signature suitable for modeling. The risk score was calculated according to the model, and the patients were divided into high- and low-risk groups according to the median risk score. Functional enrichment analysis was carried out by this group, and a model for predicting clinical prognosis was established by combining this group with clinical factors.

Results: Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) analysis showed that there were several immune-related pathways and immune infiltration differences between high- and low-risk groups. A prognostic model integrating 10 ferroptosis-related genes (FR-DEGs), and clinical factors were constructed and validated in an external cohort.

Conclusions: The FR-DEGs signature was related to immune infiltration, and a model based on FR-DEGs and clinical factors was established to predict the prognosis of patients with LUAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201541PMC
June 2021

[Immune Microenvironment Comparation Study between EGFR Mutant and EGFR Wild Type Lung Adenocarcinoma Patients Based on TCGA Database].

Zhongguo Fei Ai Za Zhi 2021 Apr;24(4):236-244

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.

Background: Lung cancer is a malignant with high incidence and mortality and adenocarcinoma is among the most popular subtypes. Epidermal growth factor receptor (EGFR) mutation is one of the most important driver mutations for lung adenocarcinoma and EGFR-tyrosine kinase inhibitor (TKI) will benefit those patients with sensitive EGFR mutations. Recently, immune checkpoint inhibitor (ICI) therapy, provide a new breakthrough treatment for lung cancer patients. Whereas immunotherapy as an emerging treatment does not benefit patients with EGFR mutations, for which mechanistic studies are poorly defined and focused on the link of EGFR mutations and programmed cell death-ligand 1 (PD-L1) expression, we speculate that the different immune microenvironment associated with the two classes of patients.

Methods: Lung adenocarcinoma datasets were collected from the Cancer Genome Atlas (TCGA) database, and clinical information and gene expression profiles were downloaded. The immune related lymphocyte infiltration in TCGA database were generated through timer 2.0 GSEA was used to analyze the difference of pathway expression between EGFR mutant patients and wild type patients.

Results: EGFR mutation was more frequently among women and never smokers. Immunoinfiltration analysis showed that patients with EGFR mutation tends to have more tumor associated fibroblasts, common myeloid progenitor cells, hematopoietic stem cells, effector CD4⁺ T cells and natural killer T cells infiltration, and less memory B cells, naïve B cells, plasma B cells, plasmacytoid dendritic cells, memory CD4⁺ T cells, CD4⁺ helper T cells 2, naive CD8⁺ T cells, CD8⁺ T cells and central memory CD8⁺ T cells infiltration. Moreover, patients with more infiltration of CD8⁺ T cells, natural killer T cells, memory B cells and hematopoietic stem cells, tends have better prognosis (Log-rank test, P=0.017, 0.0093, 0.018, 0.016). However, the patients with more CD4⁺ T th2 infiltration in the tumor tends to have worse prognosis (Log-rank test, P=0.016). Furthermore, the results of gene set enrichment analysis showed that compared with the lung adenocarcinoma patients with EGFR wild type, the three pathways positive regulation of natural killer (NK) cell-mediated immune response to tumor cells, NK cell activation involved in immune response, and NK cell-mediated immune response to tumor cells related to natural killer cells in patients with EGFR mutation were down regulated, while the pathway the positive regulation of cytokine secretion involved in immune response was up-regulated in EGFR mutation patients.

Conclusions: The tumour microenvironment of patients with EGFR mutations lacks potent tumour killing effector cells and appears dysfunctional with effector cells. This may be a potential reason for the poor efficacy of immunotherapy in patients with EGFR mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3779/j.issn.1009-3419.2021.102.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105612PMC
April 2021

Mutations Associated with No Durable Clinical Benefit to Immune Checkpoint Blockade in Non-S-Cell Lung Cancer.

Cancers (Basel) 2021 Mar 19;13(6). Epub 2021 Mar 19.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300050, China.

(1) Background: The immune checkpoint blockade (ICB) has shown promising efficacy in non-small-cell lung cancer (NSCLC) patients with significant clinical benefits and durable responses, but the overall response rate to ICBs is only 20%. The lack of responsiveness to ICBs is currently a central problem in cancer immunotherapy. (2) Methods: Four public cohorts comprising 2986 patients with NSCLC were included in the study. We screened 158 patients with NSCLC with no durable clinical benefit (NDB) to ICBs in the Rizvi cohort and identified NDB-related gene mutations in these patients using univariate and multivariate Cox regression analyses. Programmed death-ligand 1 (PD-L1) expression, tumor mutation burden (TMB), neoantigen load, tumor-infiltrating lymphocytes, and immune-related gene expression were analyzed for identifying gene mutations. A comprehensive predictive classifier model was also built to evaluate the efficacy of ICB therapy. (3) Results: Mutations in FAT1 and KEAP1 were found to correlate with NDB in patients with NSCLC to ICBs; however, the analysis suggested that only mutation in FAT1 was valuable in predicting the efficacy of ICB therapy, and that mutation in KEAP1 acted as a prognostic but not a predictive biomarker for NSCLC. Mutations in FAT1 were associated with a higher TMB and lower multiple lymphocyte infiltration, including CD8 (T-Cell Surface Glycoprotein CD8)+ T cells. We established a prognostic model according to PD-L1 expression, TMB, smoking status, treatment regimen, treatment type, and FAT1 mutation, which indicated good accuracy by receiver operating characteristic (ROC) analysis (area under the curve (AUC) for 6-months survival: 0.763; AUC for 12-months survival: 0.871). (4) Conclusions: Mutation in FAT1 may be a predictive biomarker in patients with NSCLC who exhibit NDB to ICBs. We proposed an FAT1 mutation-based model for screening more suitable NSCLC patients to receive ICBs that may contribute to individualized immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13061397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003499PMC
March 2021

Identification of small proline-rich protein 1B (SPRR1B) as a prognostically predictive biomarker for lung adenocarcinoma by integrative bioinformatic analysis.

Thorac Cancer 2021 03 26;12(6):796-806. Epub 2021 Jan 26.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Background: With the ongoing development of targeted therapy and immunotherapy in recent years, the overall five-year survival rate of NSCLC patients has not improved, and the search for novel diagnostic and prognostic markers for lung adenocarcinoma continues.

Methods: Lung adenocarcinoma (LUAD) gene expression data and relevant clinical information were obtained from the TCGA. Hub genes were identified with weighted gene co-expression network analysis (WGCNA) and protein-protein interaction network (PPI). Survival analyses were also performed using GEPIA. The 536 LUAD patients were divided into two groups according to the SPRR1B expression level and analyzed by gene set enrichment analysis (GSEA) and verified by immunoblotting. The effects of SPRR1B on cell proliferation and cell metastasis and apoptosis were evaluated by 5-ethynyl-2'-deoxyuridine (EdU) staining, colony formation assay, transwell migration and invasion assay, and flow cytometry, respectively.

Results: A total of 2269 DEGs were analyzed by WGCNA and five hub genes (CCK, FETUB, PCSK9, SPRR1B, and SPRR2D) were identified. Among them, SPRR1B was selected as one of the most significant prognostic genes in LUAD. SPRR1B was found to be highly expressed in lung adenocarcinoma cells compared with that in normal bronchial epithelial cells. In addition, silencing of SPRR1B could inhibit the cell proliferation, invasion, and migration of lung adenocarcinoma cells, but induced cell apoptosis and G2/M phase arrest in vitro. The result of GSEA and immunoblotting revealed that SPRR1B activated the MAPK signaling pathway involved in the proliferation and metastasis of lung cancer.

Conclusions: Our findings demonstrate that SPRR1B may function as a prognosis predictor in lung adenocarcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952803PMC
March 2021

A Comparison of the Short-Term Clinical Effects Between Totally Laparoscopic Radical Gastrectomy With Modified Roux-en-Y Anastomosis and Laparoscopic-Assisted Radical Gastrectomy With Roux-en-Y Anastomosis.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033820973281

Department of Gastrointestinal Surgery, Hubei Cancer Hospital, Tongji Medical College, University of Science and Technology Huazhong, Wuhan, China.

Objective: To compare the short-term clinical effects between totally laparoscopic radical gastrectomy with modified Roux-en-Y anastomosis, and laparoscopic-assisted radical gastrectomy with Roux-en-Y anastomosis; to explore the safety, feasibility and short-term effect of totally laparoscopic radical gastrectomy with modified Roux-en-Y anastomosis.

Methods: Data of 75 patients who underwent totally laparoscopic radical gastrectomy with modified Roux-en-Y anastomosis, and 95 patients who underwent laparoscopic-assisted radical gastrectomy with Roux-en-Y anastomosis by the same surgical team were analyzed. During the modified Roux-en-Y anastomosis, the stomach separation and regional lymph node dissection were completed under a laparoscope; the specimen was placed in a bag; gastrojejunostomy was completed; the subumbilicus hole was enlarged to 3 cm; the specimen was taken out; then, the proximal and distal ends of the small intestine were moved outside of the abdominal wall to complete the small intestine-small intestine end-to-side anastomosis.

Results: All 170 operations were successful. The differences in the time of anastomosis and the number of dissected lymph nodes between the 2 groups were not statistically significant (P > 0.05), but in the totally-MA group the amount of bleeding and the length of incision significantly decreased (P < 0.05). The recovery time as measured by breathing unassisted, drinking fluids and getting out of bed was significantly shorter than those in the laparoscopic-assisted group (P < 0.05), and the pain score 1 day after surgery was significantly lower than that of the laparoscopic-assisted group (P < 0.05). One case of duodenal stump leakage and 1 case of esophagojejunostomy leakage were found in the laparoscopic-assisted group. In the totally-MA group, there were no complications such as anastomotic leakage, anastomotic stenosis or anastomotic bleeding, but 2 patients with double primary carcinoma underwent joint radical resection.

Conclusion: Compared with laparoscopic-assisted surgery, totally laparoscopic radical gastrectomy with modified Roux-en-Y anastomosis has the advantages of being safer and less traumatic, with associated reductions in bleeding and pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1533033820973281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672738PMC
November 2020

Cutaneous metastasis of ascending colon cancer harboring a BRAF V600E mutation: A rare case report.

Medicine (Baltimore) 2020 May;99(21):e20026

Department of Gastrointestinal Surgery, Hubei Cancer Hospital, Tongji Medical College, University of Science and Technology, Huazhong.

Rationale: Cutaneous metastases from colorectal cancer are extremely rare and generally appear several years after diagnosis or resection of the primary colorectal tumor. Although cutaneous metastasis is unusual, it often indicates a poor prognosis.

Patient Concerns: We treated a 62-year-old woman with multiple cutaneous metastatic nodules on the chest, back, and armpit 7 months after resection of ascending colon cancer.

Diagnoses: The patient was diagnosed with cutaneous metastasis of ascending colon cancer with BRAF V600E mutation.

Interventions: After 6 cycles of fluorouracil, leucovorin, oxaliplatin, cetuximab, and emurafenib, most of the metastatic lesions had begun to shrink, and no new metastases were observed. Serum tests showed that the levels of several tumor markers were decreased.

Outcomes: The patient responded well to treatment and survived for 6.5 months after presentation with skin metastasis.

Lessons: Cutaneous metastasis of colorectal cancer with BRAF V600E mutation is a rare but important phenomenon that should not be ignored. Cutaneous metastasis of colorectal cancer frequently indicates advanced disease and poor prognosis. The SWOG 1406 program is one of the treatment options, but this needs further exploration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000020026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249915PMC
May 2020

[Apatinib Combined with CCI-779 Inhibits the Proliferation and Migration of Small Cell Lung Cancer NCI-H446 Cells In Vitro].

Zhongguo Fei Ai Za Zhi 2020 Apr 26;23(4):216-222. Epub 2020 Mar 26.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.

Background: Lung cancer is the most common malignancy world-wide. Small cell lung cancer is the deadliest subtype of lung cancer, which features such as rapid growth, early metastasis, and high vascularization. Apatinib is a vascular endothelial growth factor receptor 2 inhibitor independently developed in China, which has a significant inhibition in a variety of solid tumors. The purpose of this study is to investigate the effects of Apatinib alone or Apatinib combined with mammalian target of rapamycin (mTOR) inhibitor, CCI-779, on small cell lung cancer cell line NCI-H446 in vitro.

Methods: The small cell lung cancer cell line NCI-H446 was grew in vitro. The effects of Apatinib alone or Apatinib combined with CCI-779 on proliferation, apoptosis, cell cycle and migration of NCI-H446 small cell lung cancer cells were detected by CCK8; FACS and transwell assays were also carried out; Western blot assays were used to detect vascular endothelial growth factor and cell cycle related protein expression.

Results: CCK8 assays showed that high concentration of Apatinib could inhibit the proliferation of NCI-H446 cells. Apoptosis assays showed that high concentration of Apatinib could induce NCI-H446 cell apoptosis. Transwell assays showed that high concentration of Apatinib could inhibit NCI-H446 cell migration. After combined with mTOR inhibitor CCI-779, low concentration of Apatinib could inhibit the proliferation and migration of NCI-H446 small cell lung cancer cells and induce apoptosis.

Conclusions: Apatinib has a concentration-dependent effect on the small cell lung cancer cell line NCI-H446. High concentration of Apatinib can inhibit the proliferation and migration of NCI-H446 small cell lung cancer cells, induce apoptosis. Apatinib combined with the mTOR inhibitor CCI-779 can sensitize the NCI-H446 cells to Apatinib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3779/j.issn.1009-3419.2020.104.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210093PMC
April 2020

The interplay between GRP78 expression and Akt activation in human colon cancer cells under celecoxib treatment.

Anticancer Drugs 2015 Oct;26(9):964-73

aDepartment of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan bDepartment of General Surgery, People's Hospital, Cangzhou, Hebei cDepartment of Gastroenterology, the Central Hospital of Panjin, Liaoning, People's Republic of China.

It has been reported previously that celecoxib shows antitumor effects in many types of cancers. Here, we detected its effects on DLD-1 and SW480 (two human colon cancer cell lines) and investigated the dynamic relationship between the 78-kDa glucose-regulatory protein (GRP78) and the phosphoinositide 3-kinase (PI3K)/Akt pathway. Gene expression was detected by real-time PCR and western blot analysis; the cytotoxicity was determined by the MTT assay and flow cytometry. First, the results showed that celecoxib induced cytotoxicity in a dose-dependent and time-dependent manner. Furthermore, we found the celecoxib-triggered unfolded protein response and the bidirectional regulation of Akt activation in both cell lines. Inhibiting the Akt activation by the PI3K inhibitor LY294002 markedly enhanced GRP78 expression. Besides, silencing the GRP78 expression regulated Akt activation in a time-dependent manner and increased the induction of the C/EBP homologous protein (CHOP) as well as considerably promoted celecoxib-induced apoptosis. In conclusion, these findings provide evidence that under the celecoxib treatment, GRP78 plays a protective role by modulating Akt activation and abrogating CHOP expression. However, Akt activation can provide a feedback loop to inhibit GRP78 expression. These studies can lead to novel therapeutic strategies for human colon cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CAD.0000000000000273DOI Listing
October 2015