Publications by authors named "Xia-Hong You"

8 Publications

  • Page 1 of 1

High-Grade Inflammation Attenuates Chemosensitivity and Confers to Poor Survival of Surgical Stage III CRC Patients.

Front Oncol 2021 23;11:580455. Epub 2021 Apr 23.

Biological Resource Center, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

Heterogeneous clinical and molecular characteristics are reported in colorectal cancer (CRC) with different tumor laterality. However, the outcome of left- and right-sided patients with stage I-III CRC and the role of chronic inflammation in survival differences between them remain unclear. A prospective study including 1,181 surgical patients with stage I-III CRC was carried out to investigate the involvement of circulating fibrinogen-to-pre-albumin (Alb) ratio (FPR) and primary tumor sidedness in the clinical outcome of those patients. We further investigated the effect of FPR on adjuvant chemotherapy response and recurrence in stage III patients. Our study showed that the right tumor location was significantly associated with poor recurrence-free survival (RFS) ( = 0.04, adjusted HR = 1.41, 95% CI = 1.02-1.94) and overall survival (OS) ( = 0.04, adjusted HR = 1.55, 95% CI = 1.01-2.38) only in the stage III disease. In these patients, T4 stage distribution (83.39 vs. 70.94%, < 0.01) within right-sided cases was significantly higher than left-sided patients. Moreover, preoperative FPR within right-sidedness ( < 0.01), T4 stage ( < 0.05), and large cancer bulk (≥5 cm) ( < 0.05) subgroups was significantly elevated compared to their counterparts, and it was gradually rising following the increased cancer bulk ( trend < 0.01). High-FPR distribution (52.30 vs. 27.00%, < 0.01) within right-sided patients with the stage III disease was significantly higher than that in the left-sided cases. RFS ( < 0.01) and OS ( < 0.01) of the high-FPR patients were extremely inferior to the low-FPR cases, and the significant associations were observed when they were adjusted by other confounders including primary tumor location ( < 0.01, adjusted HR = 1.96, 95% CI = 1.42-2.70 for RFS; < 0.01, adjusted HR = 2.44, 95% CI = 1.59-3.75 for OS). Additionally, RFS of adjuvant chemotherapy-treated high-FPR patients was superior to the patients without chemotherapy ( = 0.01) but was inferior to the low-FPR patients undergoing the treatment, especially in the 5-FU- and XELOX-treated subgroup. These findings indicate that chronic high-grade inflammation weakens chemotherapy efficacy and contributes to the poor prognosis of stage III surgical CRC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.580455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103203PMC
April 2021

A Novel Prognostic Score Based on for Predicting CRC Survival.

Pharmgenomics Pers Med 2020 16;13:735-747. Epub 2020 Dec 16.

Jiangxi Province Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, People's Republic of China.

Background: Colorectal cancer (CRC) is one of the lethal malignant tumors worldwide. However, the underlying mechanism of CRC and its biomarkers remain unclear. The aim of this study was to identify the key genes associated with CRC and to further explore their prognostic significance.

Methods: Four expression profile datasets (GSE41657, GSE74602, GSE113513, and GSE40967) downloaded from Gene Expression Omnibus (GEO) and one RNAseq dataset of CRC from The Cancer Genome Atlas (TCGA) database were included in our study. The Cox model was utilized for univariate or multivariate survival analysis. GEPIA and HAP database were adopted for verification of DEGs (). The decision curve analysis (DCA) and time-dependent ROC were chosen for evaluating the prognostic effectiveness of biomarkers.

Results: In total, 88 differentially expressed genes (DEGs) were identified, and the GO and KEGG enrichment analyses of DEGs were processed. After, the protein-protein interaction (PPI) network was constructed and 15 hub genes including were identified. The differential expression of between tumor and normal colorectal tissues were further verified in GEPIA and HAP database. Subsequent survival indicated that expression of is negatively correlated with overall survival of OS and is an independent prognostic factor for CRC patients. Furthermore, the construction of a prognostic score containing , TNM stage and age exhibited superior effectiveness for predicting long-term survival of CRC patients. Additionally, our results were verified using the GSE40967 dataset, which indicated an improved performance of combined risk score based on for predicting OS of CRC patients.

Conclusion: is a potential parameter for predicting prognosis in CRC. Furthermore, a combination of , TNM stage, and age allows improved prognosis of CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/PGPM.S275941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751443PMC
December 2020

Optimization of urinary small extracellular vesicle isolation protocols: implications in early diagnosis, stratification, treatment and prognosis of diseases in the era of personalized medicine.

Am J Transl Res 2020 15;12(10):6302-6313. Epub 2020 Oct 15.

Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University Nanchang 330006, Jiangxi, China.

Extracellular vesicles isolation from urine was severely interfered by polymeric Tamm-Harsefall protein due to its ability to entrap exosome. Studies had been reported to optimize the extraction of urine extracellular vesicles by using reducing agents, surfactants, salt precipitation or ultrafiltration, but rarely based on highly specific purification methods. We optimized the density gradient centrifugation method for the isolation of urinary small extracellular vesicles (sEV) and compared seven differential centrifugation protocols to obtain the high-yield and high-purity sEV isolation procedures. Our study showed Tris sucrose gradient centrifugation at 25°C had more concentrated distribution of exosomal marker in the gradient compared to Tris sucrose gradient centrifugation at 4°C and PBS sucrose gradient centrifugation. Dissolving the 16000 g pellet using Tris, Nonidet™ P 40 or Dithiothreitol then pooling the supernatants did not increase the exosomal markers and number of nanoparticles in sEV preparation compared to the control and PBS groups. Differential centrifugation at room temperature without ultrafiltration recovered more exosome-like vesicles, exosomal markers and nanoparticles than that at 4°C or combining ultrafiltration. Differential centrifugation at RT without ultrafiltration and salt precipitation recovered the highest number of nanoparticles than other protocols. However, differential centrifugation at RT combining 100 kd ultrafiltration obtained the highest purity of sEV calculated by Nanoparticle number/Total protein. In conclusion, we had established two urinary sEV isolation procedures that can recovered higher yield of sEV and more pure preparation of sEV. It is not recommended to treating 16000 g pellet with reducing agents or surfactants to increase the yield of sEV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653599PMC
October 2020

Chemotherapy plus bevacizumab as an optimal first-line therapeutic treatment for patients with right-sided metastatic colon cancer: a meta-analysis of first-line clinical trials.

ESMO Open 2020 03;4(Suppl 2)

Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China

Background: Monoclonal antibodies of anti-epidermal growth factor receptor (EGFR) have been recommended as first-line therapy for patients with left-sided metastatic colorectal cancer (mCRC) with wild-type . The effect of tumour laterality on antivascular endothelial growth factor antibody and how to optimise targeted therapies for the right-sided cases remain controversial.

Patients And Methods: A comprehensive meta-analysis enrolling 16 first-line clinical trials was performed to evaluate the efficacy of chemotherapy alone and chemotherapy plus targeted therapies for patients with mCRC with right primary tumour site, and we validated the results in metastatic setting (14 trials containing 4306 patients with unresectable mCRC).

Results: Here, we found that progression-free survival (PFS) (combined HR 1.30, 95% CI 1.17 to 1.44) and overall survival (OS) (combined HR 1.46, 95% CI 1.32 to 1.62) of the right-sided patients were significantly inferior to the left-sided individuals receiving chemotherapy alone in overall population, regardless of race. Similar results were also observed in metastatic setting. OS of patients with left-sided mCRC receiving chemotherapy plus bevacizumab was superior to the right-sided individuals (combined median survival ratio (MSR)=1.23, 95% CI 1.08 to 1.39 for overall population; combined MSR=1.23, 95% CI 1.05 to 1.45 for metastatic setting), especially for wild-type and mixed population. Moreover, the right-sided patients benefited more from chemotherapy plus bevacizumab comparing with chemotherapy alone in both overall population and metastatic setting. Importantly, the -wild right-sided patients achieved longer PFS (combined HR 0.67, 95% CI 0.52 to 0.88) and OS (combined HR 0.74, 95% CI 0.56 to 0.98) from chemotherapy plus bevacizumab comparing with chemotherapy associated with anti-EGFR agents.

Conclusions: Patients with right-sided mCRC show impaired chemosensitivity, and chemotherapy plus bevacizumab can be an optimal first-line therapeutic regimen for the wild patients with right-sided mCRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/esmoopen-2019-000605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064070PMC
March 2020

K562 cell-derived exosomes suppress the adhesive function of bone marrow mesenchymal stem cells via delivery of miR-711.

Biochem Biophys Res Commun 2020 01 31;521(3):584-589. Epub 2019 Oct 31.

Jiangxi Province Key Laboratory of Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, No.1 Min De Road, Nanchang, 330006, China. Electronic address:

A failure of bone marrow mesenchymal stem cells (BM-MSCs) to adhere to hematopoietic cells is an essential cause of the progression of chronic myelogenous leukemia and is also a cause of failure of bone marrow (BM) transplantation, but the exact mechanisms of this have not been fully elucidated. Recent studies have indicated that microRNAs (miRNAs) are contained in leukemia-derived exosomes and are involved in modulating the BM microenvironment. In this study, we found that K562 cell-derived exosomes transfer miR-711 to BM-MSCs and suppress the adhesive function of BM-MSCs. Using qRT-PCR, we also confirmed a significantly higher level of miR-711 in exosomes derived from K562 cells than in exosomes derived from parental cells. The BM-MSCs co-cultured with exosomes derived from K562 cells showed a lower adhesion rate than did controls. We further demonstrated that exosomal transfer of miR-711 induced decreased adhesive abilities by inhibiting expression of adhesion molecule CD44 in BM-MSCs. In conclusion, our study reveals that K562 cell-derived exosomal miR-711 can be transferred to BM-MSCs and weaken adhesive abilities by silencing the expression of the adhesion molecule CD44.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2019.10.096DOI Listing
January 2020

Albumin to fibrinogen ratio and fibrinogen to pre-albumin ratio are economical, simple and promising prognostic factors for solid malignancy.

J Thorac Dis 2019 Sep;11(Suppl 15):S2036-S2038

Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd.2019.08.96DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783761PMC
September 2019

Primary Tumor Sidedness Predicts Bevacizumab Benefit in Metastatic Colorectal Cancer Patients.

Front Oncol 2019 14;9:723. Epub 2019 Aug 14.

Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China.

The emerging debate between primary tumor location and clinical outcome of bevacizumab treated metastatic colorectal cancer (mCRC) continues. The aim of the present study is to investigate the association between the primary tumor location and clinical outcome of 115 mCRC patients receiving bevacizumab based treatment. A meta-analysis including 21 studies was carried out to confirm the conclusion. In our prospective study, we found that right-sided mCRC commonly occurred in older cases ( = 0.03) with multiple-site metastasis ( = 0.03). Progression-free survival (PFS) of the left-sided patients undergoing bevacizumab plus a FOLFIRI regimen was superior to the right-sided cases ( = 0.03, crude HR = 0.31, 95%CI = 0.11-0.87; adjusted HR = 0.21, 95%CI = 0.06-0.66). The meta-analysis confirmed that efficacy of bevacizumab-based treatment in left-sided mCRC patients was better than the right-sided cases in the overall population ( = 0.24, combined OR = 1.36, 95%CI = 1.07-1.72), / wild-type ( = 0.19, combined OR = 1.66, 95%CI = 1.17-2.34), clinical trial ( = 0.23, combined OR = 1.42, 95%CI = 1.07-1.88), Caucasian population ( = 0.18, combined OR = 1.37, 95%CI = 1.02-1.85) and first-line ( = 0.19, combined OR = 1.48, 95%CI = 1.13-1.96) subgroups. Improved survival of bevacizumab plus chemotherapy treated left-sided mCRC patients was observed in the overall population [ < 0.01, combined MSR = 1.09, 95%CI = 1.00-1.18 for PFS; < 0.01, combined MSR = 1.24, 95%CI = 1.13-1.36 for overall survival (OS)], especially in the wild-type ( = 0.09, combined MSR = 1.10, 95%CI = 1.03-1.19 for PFS; = 0.02, combined MSR = 1.34, 95%CI = 1.21-1.49 for OS). These findings indicate that primary tumor sidedness can predict clinical outcome of bevacizumab-treated wild-type mCRC patients and the left-sided patients may benefit more from bevacizumab plus FOLFIRI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.00723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702298PMC
August 2019

Elevated FPR confers to radiochemoresistance and predicts clinical efficacy and outcome of metastatic colorectal cancer patients.

Aging (Albany NY) 2019 03;11(6):1716-1732

Department of Clinical Laboratory, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchan, Jiangxi 330006, China.

Association of chronic inflammation, primary tumor sidedness, adjuvant therapy and survival of metastatic colorectal cancer (mCRC) remains unclear. Circulating inflammatory cell, fibrinogen (Fib), albumin (Alb), pre-albumin (pAlb), Alb/Fib (AFR) and Fib/pAlb (FPR) were detected, and clinical outcome was obtained to determine the predictive, prognostic and monitoring roles of them in discovery and validation cohort. We found that elevated FPR, low AFR and poor survival was observed in right-sided mCRC comparing to the left-sided disease, elevated FPR harbored the highest areas under curve to independently predict poor progression-free survival and overall survival in overall and left-sided mCRC case in two cohorts. No survival difference was examined between the two-sided patients in subgroups stratified by FPR. Radiochemoresistance was observed in high FPR case. However, the patient could benefit from bevacizumab plus radiochemotherapy. Low FPR patient showed the best survival with treatment of palliative resection plus radiochemotherapy. Moreover, circulating FPR was significantly increased ahead imaging confirmed progression and it reached up to the highest value within three months before death. Additionally, c-indexes of the prognostic nomograms including FPR were significantly higher than those without it. These findings indicated that FPR was an effective and independent factor to predict progression, prognosis and to precisely identify the patient to receive optimal therapeutic regimen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.101864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461181PMC
March 2019
-->