1.Effect of type 2 diabetes on middle cerebral artery occlusion-induced focal cerebral ischemia
Ying JIA ; Yuejia SONG ; Likun ZAN ; Guoxin TENG ; Na LIU ; Min ZHOU ; Yulan SUN ; Jiping QI
Chinese Journal of Neurology 2011;44(4):238-241
Objective To study the function of vascular endothelial growth factor (VEGF) in type 2 diabetes model rats and its effect on focal cerebral ischemia induced by middle cerebral artery occlusion in these rats. Methods Focal cerebral ischemia was induced by middle cerebral artery occlusion for 6 hours in type 2 diabetes rats and normal control rats.Blood vessels morphology was examined by ink perfusion,infarct size was measured by TTC and expression of VEGF and CD34 were evaluated by immunohistochemistry staining. Results Ink perfusion revealed increased number of small vessels in type 2 diabetes rats. Infarct size was significantly smaller in type 2 diabetes rats ( ( 80. 07 ± 11.21 ) mm3 ) than that in normal controls ((98. 91 ± 14. 86) mm3,t = 2.48,P = 0. 0326). There were more hemorrhage lesions in the ischemic hemisphere in type 2 diabetes rats when comparing with the controls. VEGF and CD34 showed significantly higher expression in type 2 diabetes rats than in normal controls. Conclusions High expression of VEGF and CD34 are found in type 2 diabetes rats after middle cerebral artery occlusion. There is cerebrolvascular remodeling in diabetes rats. While this diabetes-induced remodeling appears to prevent infarct expansion,the changes also increase the risk of hemorrhagic transformation. The latter may result in poor prognosis.
2.Expression of insulin-like growth factor 1 and its receptors in colorectal cancer and their significances
Jing JU ; Cunzhi HAN ; Likun ZAN ; Yixin LI ; Bo JIANG
Cancer Research and Clinic 2017;29(9):593-597
Objective To investigate the expression of insulin-like growth factor 1 (IGF-1), insulin growth factor receptor 1(IGF-1R)and insulin growth factor receptor 2(IGF-2R)in colorectal cancer, and their relationship with the relevant clinicopathological factors. Methods Immunohistochemical SP method was used to detect the expression of IGF-1,IGF-1R and IGF-2R in 154 cases of colorectal cancer tissues,58 cases of benign disease tissues (colorectal adenoma, polyps) and 90 normal tissues. Results The positive rate of IGF-1 and IGF-1R expression in colorectal cancer tissues [93.5%(144/154), 70.1%(108/154)] was higher than that in benign diseases [51.7%(30/58), 51.7%(30/58)] and adjacent normal tissues [18.9%(17/90), 35.6%(32/90)] (P=0.001). The positive expression rate of IGF-1 and IGF-1R in colorectal cancer tissue, benign disease tissue and adjacent normal tissues decreased gradually, and there was significant difference between any two groups (P<0.05). The positive expression rate of IGF-2R had no significant difference between any two groups (P>0.05). IGF-2R was significantly different between any two groups (P<0.05). The expression of IGF-1R and IGF-2R in colorectal cancer tissues were not significantly correlated with gender, location, tumor size, family history, depth of tumor invasion and local lymph node metastasis (all P>0.05).IGF-1 was positively correlated with the body mass index(r=0.169,P=0.036).IGF-2R was negatively correlated with age (r=-0.196, P=0.015), and positively correlated with TNM staging in patients with colorectal cancer (r=0.227, P=0.005). The expression of IGF-1 was positively correlated with IGF-1R (r=0.281, P=0.000 1). There was no significant correlation between IGF-1 and IGF-2R in cancer tissues (P>0.05). Conclusion IGF-1 and IGF-1R may promote the occurrence of colorectal cancer, and IGF-2R may be associated with the progress of colorectal cancer,and obesity is a risk factor for incidence of colorectal cancer.
3.Detection of PIK3CA gene mutation and its related prognosis in colorectal cancer based on next-generation sequencing
Xiao PENG ; Xin ZHANG ; Hongxia LU ; Lulu SHEN ; Ning GAO ; Likun ZAN
Chinese Journal of Pathology 2024;53(7):716-721
Objectives:To investigate the mutation of PIK3CA in colorectal cancer and to analyze their clinicopathological features, and evaluate their role in clinical treatment and prognostication.Methods:A total of 128 paraffin-embbeded tissue samples of colorectal cancer from Shanxi Cancer Hospital from 2018 to 2021 were collected. DNA was extracted from the samples, and next-generation sequencing (NGS) was used to detect PIK3CA mutation. The relationship between PIK3CA mutation, their clinicopathological features, and prognosis were analyzed.Results:Among the 128 colorectal cancer samples, there were 75 males and 53 females; with aged range 32-86 years, median 61.5 years, 27 (21.09%) had PIK3CA mutations. Colorectal cancer with PIK3CA mutation was more likely to occur in male patients ( P=0.007), which was related to tumor site ( P=0.032), tumor size ( P=0.029) and TP53 wild-type ( P=0.001). The common site mutations of PIK3CA mostly occurred in tumors with tumor mutation burden≥10 Muts/Mb ( P=0.031).PIK3CA mutation had no significant effect on the survival prognosis of patients, but the efficacy of anti-angiogenic therapy was poor in these patients. Conclusions:PIK3CA mutation is a common mutation in colorectal cancer and plays an important role in the occurrence and development of colorectal cancer. PIK3CA mutation may lead to resistance to anti-angiogenic drugs in colorectal cancer, but its impact on survival and prognosis to patients needs further study.
4.Analysis of VSIG4 expression in clear cell renal cell carcinoma and its correlation with tumor infiltrating immune cells
Hangfeng LIU ; Shenglu LIU ; Lianrui DUAN ; Likun ZAN ; Yanjie MA ; Lijun YANG
Chinese Journal of Immunology 2024;40(5):918-924
Objective:To explore expression of VSIG4 in clear cell renal cell carcinoma(ccRCC)and its correlation with immune cells infiltration and prognosis.Methods:RNA-seq data of ccRCC and corresponding clinical data of patients were downloaded from The Cancer Genome Atlas(TCGA)database.Wilcoxon rank-sum test was used to analyze VSIG4 mRNA expression in ccRCC and normal renal tissues.Correlation between VSIG4 expression and clinicopathological parameters was analyzed by Wilcoxon rank-sum or Kruskal-Wallis rank-sum test.Kaplan-Meier method was used to analyze the correlation between VSIG4 expression and progno-sis of patients.Gene set enrichment analysis(GSEA)was used to explore the signaling pathway of VSIG4 in ccRCC.Correlation between VSIG4 level and tumor infiltrating immune cells was analyzed via CIBERSORT in R software.Western blotting was used to detect VSIG4 protein level in human renal epithelial cell line 293T,and human renal carcinoma cell line ACHN,A498,786-O and OS-RC-2.Results:Expression level of VSIG4 in ccRCC was significantly higher than that in normal tissues(P<0.05).VSIG4 expression was significantly correlated with the stages of distant metastasis and lymph node metastasis(P<0.05).Overall survival rate of patients with high VSIG4 expression was significantly lower than that of patients with low expression(P<0.05).GSEA enrichment analysis showed that VSIG4 was mainly enriched in apoptosis,chemokine signaling pathway,cell adhesion molecules and other signaling path-ways.VSIG4 expression was negatively correlated with M1 macrophages(r<0,P<0.05),while positively correlated with M2 macro-phages(r>0,P<0.05).Western blotting results showed that expression of VSIG4 in renal cell carcinoma cells was higher than that in normal renal cells.Conclusion:VSIG4 is highly expressed in ccRCC,and is negatively associated with prognosis,which may become a prognostic biomarker for ccRCC patients.
5.Clinical characteristics and survival analysis of primary thyroid lymphoma
Zhiqiang ZHAO ; Meng XING ; Yu QIAO ; Xuli YAN ; Qinchuan YU ; Likun ZAN ; Liping SU ; Lieyang WANG
Cancer Research and Clinic 2022;34(11):835-838
Objective:To investigate the clinical characteristics of primary thyroid lymphoma (PTL) and the differences in clinical manifestations and survival between the two main pathological subtypes of PTL.Methods:The clinical data of 52 patients with PTL diagnosed in Shanxi Province Cancer Hospital from January 2011 to January 2022 were retrospectively analyzed. The clinical characteristics and survival between the two main pathological subtypes [diffuse large B-cell lymphoma (DLBCL) and mucosa-associated lymphoid tissue lymphoma (MALT)] were compared.Results:Among 52 PTL patients, there were 12 males and 40 females, with a median age of 65 years old (34-83 years old). All patients presented with anterior cervical mass at the time of visit. MALT was diagnosed in 12 cases (23.1%). DLBCL was diagnosed in 37 cases (71.2%), of which 5 cases were double/triple expression lymphoma. B-cell lymphoma (unclassified) was diagnosed in 2 cases (3.8%). Follicular lymphoma (FL) was diagnosed in 1 case (1.9%). There was statistical difference in the proportion of patients with cervical lymph node enlargement between MALT and DLBCL patients [66.7% (8/12) vs. 94.6% (35/37), χ2 = 4.23, P < 0.05]. The 3-year OS rates of MALT and DLBCL patients were 90.9% and 73.9%, and the difference in OS between the two groups of patients was statistically significant ( χ2 = 5.11, P = 0.024). Conclusions:Pathological subtypes of PTL are related to the prognosis of patients.
6.Clinicopathological analysis of gastric adenocarcinoma with elevated serum alpha-fetoprotein and enteroblastic differentiation
Likun ZAN ; Lulu SHEN ; Xin ZHANG ; Ning GAO ; Baoguo TIAN ; Xiaoxin GENG ; Xiao PENG ; Jiawen LI ; Peng BU ; Guohai ZHAO
Chinese Journal of Oncology 2024;46(7):686-695
Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P<0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P<0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.
7.Clinicopathological analysis of gastric adenocarcinoma with elevated serum alpha-fetoprotein and enteroblastic differentiation
Likun ZAN ; Lulu SHEN ; Xin ZHANG ; Ning GAO ; Baoguo TIAN ; Xiaoxin GENG ; Xiao PENG ; Jiawen LI ; Peng BU ; Guohai ZHAO
Chinese Journal of Oncology 2024;46(7):686-695
Objective:To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED).Methods:The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis.Results:Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177- GNAS, AIM1- FGFR3, and EPHA6- ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis ( P<0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone ( P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone ( P<0.05). Conclusions:Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.
8. Impact of metabolic syndrome on clinicopathological characteristics and survival of patients with colorectal cancer
Xin ZHANG ; Bo JIANG ; Likun ZAN ; Jing JU ; Cunzhi HAN ; Yan WANG ; Lili DU
Chinese Journal of General Practitioners 2019;18(12):1141-1146
Objective:
To examine the impact of metabolic syndrome (MS) on the clinicopathological characteristics and prognosis of patients with colorectal cancer (CRC).
Methods:
The clinical data of 650 patients with CRC admitted in Shanxi Provincial Cancer Hospital between January 2010 and December 2011 were retrospectively analyzed. Among 650 patients there were 190 cases complicated with MS (MS group) and 460 cases without MS (non-MS group), the clinicopathological features and prognosis were compared between two groups.
Results:
The serum insulin and insulin-like growth factor-1 (IGF-1) levels in MS group were significantly higher than those in non-MS group [(9.2±4.7)