1.An analysis on clinical features and prognostic factors of gastrointestinal stromal tumors
Jiehua LI ; Haitian ZHANG ; Zhibai CHEN ; Ka SU
Chinese Journal of General Surgery 2013;(5):360-363
Objective To study the prognostic factors of gastrointestinal stromal tumors (GIST).Methods A total of 144 GIST patients treated at the First Affiliated Hospital of Guangxi Medical University between January 1996 and December 2011 were analyzed restrospectively.Kaplan-Meier,log-rank test and Cox regression model were used.Results The overall 5-year survival was 59.6%.Log-rank univariate survival analysis showed that the primary location,tumor size,metastasis,operational method,type of tumor cells,invasion of the surrounding organs and tissues,invasion of the smooth muscle,cellularity of the tumor,mitotic counts of the tumor cells,Ki-67 labeling index,P53 expression and targeting therapy were significant prognostic factors (P < 0.05).Cox regression model showed that tumor size,metastasis,operational method,surrounding organs and tissues invasion,cellularity of the tumor,mitotic counts of the tumor cells,P53 and targeting therapy were essential to improve the survival.Conclusions The study suggests that early diagnosis and comprehensive treatment consisting of operation and targeting therapy can significantly improve the survival of GIST.
2.A study on the hepatic artery lymph node micrometastases of distal gastric cancer
Yuan HUANG ; Jinling LIN ; Chao LIU ; Zhibai CHEN
Chinese Journal of General Surgery 2011;26(9):717-720
ObjectiveTo study the dissecting necessity of lymph node around normal and abnormal hepatic artery in distal gastric cancer undergoing D2 lymphadenectomy.MethodsSixty gastric cancer patients receiving distal D2 lymphadenectomy by the same surgeon between June 2008 to June 2010 at the Department of Gastrointestinal Surgery, First Affiliated Hospital of the Guangxi Medical University were included in this study. The lymph adipose tissue around the anatomically normal and aberrant hepatic artery was carefully dissected, and the lymph nodes sent for recombinant human cytokeratin 20 (CK20) and carcino-embryonicantigen( CEA )micrometastasisimmunohistochemistry.ResultsWiththe micrometastasis immunohistochemistry of CK20 and CEA, we found the metastasise rate of lymph node around the normal hepatic artery was 27%.Patient age, tumor size, Borrmann type, TNM staging were correlated with the lymph node metastase. There were 7 cases with abnormal hepatic artery originating from the superior mesenteric artery. The hepatic artery ran in front of the pancreas in 1 case and behind the pancreas in 6 cases. We found there are no metastases in the lymph adipose tissue surrounding the abnormal artery.ConclusionsCK20,CEA are suitable immunohistochemical targets for estimating the lymph node micrometastasis. In distal gastric cancer age at 60 or older years, tumor larger than 3 cm and Borrmann Ⅲ-Ⅳ type were risk factors for metastasis of lymph nodes around normal hepatic artery, while aberrant hepatic arteries originating from the superior mesenteric artery are much less likely to have positive lymph nodes in D2 lymphadenectomy.
3.Multiple gene mutation and prognostic factors in gastrointestinal stromal tumors
Jiehua LI ; Haitian ZHANG ; Zhibai CHEN ; Xianghua WU
Chinese Journal of General Surgery 2017;32(7):569-573
Objective To investigate the status and significance of KIT,PDGFRA and DOG1 gene mutation in gastrointestinal stromal tumors (GIST).Methods 100 GIST patients treated in the First Affiliated Hospital of Guangxi Medical University between May 2002 and May 2013 were analyzed restrospectively.DNA was isolated and amplified for the all exons of KIT,PDGFRA and DOG1.Each PCR product was sequenced to find the position and type of mutation.Results KIT mutations were identified in 75 cases (75%).PDGFRA mutations were found in 16 cases (16%).No DOG1 mutations were found.The overall 5-year survival was 58.8%.Log-rank univariate survival analysis showed that the primary location,tumor size,metastasis,operational mode,type of tumor cells,invasion of the smrounding organs,invasion of the smooth muscle,mitotic counts of the tumor cells,deletions in exon 11 KIT and targeting therapy were significant prognostic factors (all P < 0.05).COX regression model showed that tumor size,metastasis,operational method,invasion of the surrounding organs,mitotic counts of the tumor cehs,deletions in exon 11 KIT and targeting therapy were related to prognosis.Conclusion KIT and PDGFRA mutations are mutually exclusive.The overexpression mechanism of DOG1 is not related to DOG1 gene mutation.The related gene mutations affect the prognosis of GIST.
4.Mechanism study of KCMF1 promoting proliferation and NF-κB signaling transduction in colorectal cancer cells
Zhibai WU ; Guiqin XU ; Li ZHANG ; Zhaojuan YANG ; Yun LIU ; Kun JIAO ; Zehong CHEN ; Chen XU ; You ZUO ; Ningqian ZHENG ; Zhiqian YE ; Yongzhong LIU
China Oncology 2024;34(11):987-997
Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P<0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P<0.01),and was positively associated with CRC clinical stage(P<0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P<0.001),induced cell apoptosis(P<0.001),and led to cell cycle arrest in G1 phase(P<0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P<0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P<0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P<0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.
5.The expression of BMP8A in papillary thyroid carcinoma and its correlation with cervical lymph node metastasis
Xueyu ZENG ; Zhu CHEN ; Min MAO ; Zhibai CHEN ; Chunyu CHEN ; Wenlong CAO ; Jiehua LI
Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(3):443-447,452
【Objective】 To investigate the expression of BMP8A in papillary thyroid carcinoma (PTC) and the relationship between its expression level and clinicopathological features of PTC patients. 【Methods】 Based on TCGA and GEO databases, we analyzed and screened BMP8A, one differentially expressed gene related to PTC. From April 2019 to October 2019, 35 cases of thyroid papillary carcinoma and the tumor-adjacent tissues were collected from the Department of Gastrointestinal Gland Surgery, the First Affiliated Hospital of Guangxi Medical University. Real-time PCR was used to detect the expression of BMP8A in PTC and tumor-adjacent tissues, and the relationship between different expression levels and clinicopathological features of the patients was analyzed and compared. Then, we used Western blotting for verification. 【Results】 Both Real-time PCR and Western blotting analyses proved that the expression of BMP8A in PTC was significantly lower than that in the tumor-adjacent tissues (P<0.05), and the expression of BMP8A was also significantly decreased in PTC tissues with cervical lymph node metastasis compared with those without metastasis(P<0.05). 【Conclusion】 BMP8A has a low expression in papillary thyroid carcinoma, and its expression level is related to cervical lymph node metastasis. BMP8A may be a suppressor gene of PTC. This may provide a new direction for further exploring the mechanism of cervical lymph node metastasis in PTC and preventing recurrence after surgery.