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Xp11 translocation renal cell carcinoma is a rare renal cell carcinoma subtype harboring a TFE3 translocation, which is grouped into the MiT family translocation renal cell carcinomas together with t (6;11) translocation renal cell carcinomas. With the de-velopment and application of immunohistochemistry, fluorescence in situ hybridization, reverse transcription-polymerase chain reac-tion, and RNA sequencing, increasingly more Xp11 translocation renal cell carcinomas have been diagnosed and studied, and many new insights have been elucidated and advances have been made in clinicopathology, molecular genetics, and clinical treatment. The latest progress in Xp11 translocation renal cell carcinoma research is introduced and reviewed in this paper.
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Objective: To detect the expression of SVEP1, PKHD1 and P53 in primary liver cancer tissues by immunohistochemistry for predicting the recurrence of liver cancer. Methods: The clinical data of 103 patients with primary liver cancer who underwent surgical resection at Tianjin Medical University Cancer Institute and Hospital were gathered from January 2013 to January 2014 and analyzed retrospectively. Expression values of three different proteins were used to develop separate immunohistochemical scores for the prog-nosis of recurrence in patients. The patients were classified into either a high-risk or a low-risk group based on their immunohisto-chemical scores through ROC curve analysis. The difference in recurrence ratio between the two groups was then compared using the common research index of disease-free survival (DFS). Results: The median age of the total patients was 55 years (range 21-88 years), the median AFP level was 70.6 (range 1.03-718840.0) μg/L, the median CA19-9 level was 22.89 (range 0.6-1000.0) kU/L, and the medi-an tumor size was 4.5 (1.0-27.0) cm. The expression levels of SVEP1, PKHD1, and P53 in primary liver tumors were detected by immu-nohistochemistry and assigned separate immunohistochemical scores. The areas under the ROC curves of the immunohistochemical scores of SVEP1, PKHD1, and P53 were 0.861, 0.829, and 0.716, respectively. The critical values of SVEP1, PKHD1, and P53 were 4, 4, and 1 point, respectively (P<0.001). The three-year DFS rates among the SVEP1 high-risk (expression≤4 points) and low-risk groups (expression>4 points) were 4.1% and 51.7%, respectively. Similarly, the three-year survival rates among the PKHD1 high-risk (expres-sion≤4 points) and low-risk groups (expression>4 points) were 5.3% and 51.9%, respectively. The three-year DFS rates among the P53 high-risk (expression>1 point) and the low-risk group (expression≤1 point) were 6.3% and 27.3%, respectively. The survival differenc-es between all the pairs were statistically significant (P<0.001,<0.001, and 0.003 respectively). When PKHD1 was used in combination with SVEP1, the ROC curve had an area of 0.897 (P<0.001) with a sensitivity of 76.5% and a specificity of 94.4%. Conclusions: The accu-racy of P53 data for predicting primary liver cancer recurrence is insufficient and therefore it is not recommended for use. SVEP1 and PKHD1 data achieve sufficient accuracy for predicting the recurrence of primary liver cancer. Since SVEP1 data impart a higher specifici-ty and PKHD1 data impart a higher sensitivity to the prognosis scores, the combined use of the two markers is better than being used individually.
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Objective:To explore the diagnostic value of ultrasound-guided fine needle aspiration biopsy(US-FNAB)for thyroid nod-ules.Methods:The clinical characteristics and cytopathological diagnosis of patients with thyroid nodules in Tianjin Medical University General Hospital were analyzed retrospectively;the results of the cytopathological and pathological diagnoses were compared and an-alyzed.Results:Of the 1,241 US-FNAB samples,the ratio of men to women with thyroid nodules was 1:3.83(257/984).The incidence of thyroid nodules gradually increased from the age of 20 years and declined after the age of 60 years.The nodules,which were less than or equal to 1.0 cm in size,accounted for 51.57%(640 cases),and Thyroid Imaging Reporting And Data System(TIRADS)classifica-tion 4 accounted for 86.38%(1 072 cases).Of cyto-pathological diagnoses,22.00%(273 cases)were non-diagnostic,9.75%(121 cases) were benign,30.62%(380 cases)were atypia with undetermined significance,32.15%(399 cases)were suspicious for malignancy,and 5.48%(68 cases)were malignant.In the 302 patients who underwent surgery,the number of cases of clear diagnoses,unavailable di-agnoses,and atypia of undetermined significance were 203,21,and 78,respectively.In the 203 cases of clear diagnoses,the sensitivi-ty,specificity,positive predictive value,negative predictive value,precision,and misdiagnoses following US-FNAB of thyroid nodules were 100.00%(201/201),50.00%(1/2),99.50%(201/202),100.00%(1/1),99.51%(202/203),and 0.49%(1/203),respectively.In the 78 cases that were atypia of undetermined significance,the malignancy rate was 70.51%.Whether the atypia of undetermined signifi-cance was malignant or not was related to the TIRADS classification(P<0.05),and not related to the age,sex,tumor size,or location of the nodules(P>0.05).Conclusions:US-FNAB has high diagnostic value for thyroid nodules and is worthy of being popularized widely.If it replaced some intra-operative frozen sectioning procedures,it may reduce intra-operative waiting time and financial burden of pa-tients.
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Objective:To explore the clinicopathological characteristics and prognostic factors of neuroendocrine neoplasms(NENs)at different sites in the digestive system.Methods:The clinicopathological parameters and follow-up data were collected from 284 pa-tients with NENs in the digestive system in Tianjin Medical University Cancer Institute and Hospital from March 2011 to December 2015.The incidence and clinicopathological features were compared between the cases of NENs at different sites and survival analysis was performed.Results:In this study,NENs were detected mostly frequently in the pancreas,followed by the colorectum and stom-ach.In the pancreas,neuroendocrine tumor(NET)G1(51.8%)and G2(35.8%)accounted for a large proportion of NENs.World Health Organization(WHO)grades were related to lymph node metastasis,adjacent organ invasion,and nerve invasion(P<0.05 for all)but were not associated with the overall survival time of the patients.The patients with pancreatic NENs with distant metastasis had poor overall survival(P<0.05).Regarding colorectal NENs,most patients had NET G1(82.5%),and the majority of patients were cured with endoscopic or transanal resection.Patients with NENs,lymph node metastasis,and distant metastasis had poor overall survival(P<0.05 for all).The ratio of male-to-female patients,proportion of patients aged older than 40 years,prevalence of neuroendocrine carci-nomas(NECs)and mixed adenoneuroendocrine carcinomas(MANECs),presence of lymph node and distant metastasis,and presence of advanced stage tumors were greater in patients with gastric NENs than in patients with pancreatic and colorectal NENs(P<0.05 for all).WHO grades and lymph node metastasis were associated with the overall survival time of patients with gastric NENs(P<0.05 for both).Conclusions:NENs in the digestive system are a group of heterogeneous tumors with different clinicopathological features at different sites.The distribution and clinicopathological features of Chinese patients with NENs in the digestive system are different from those of European and American patients.More multicenter studies with large sample sizes are still needed to understand the bi-ological behaviors and prognostic factors of NENs at different sites in the digestive system.
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Long noncoding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides. Most lncRNAs have pro-nounced oncogenic effects associated with tumorigenesis and progression, promoting the proliferation, migration, invasion, and me-tastasis of tumor cells. The specific lncRNAs expression in particular types of cancers makes them promising diagnostic and prognostic biomarkers. Currently, studies on lncRNAs expression, functions, and mechanisms have attracted considerable attention in cancer re-search. However, these studies mainly focus on epitheliogenic malignant tumors. In this review, we outline the current state of infor-mation on lncRNAs and research progress on its role in haematopoietic and lymphoid tissue tumors.
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Objective:This study aims to determine the suitable cell line to be used in isolating cancer stem cells by comparing the characteristics of tumor stem cells in renal cell carcinoma cell lines SN12C and 786-O. Methods:The rate of sphere formation in SN12C and 786-O cells was determined in serum-free medium (SFM). The expression levels of CD133, CD44, Nanog, and Oct3/4 were investi-gated through flow cytometry. Moreover, the tumorigenicity of spheroid cell that originated from SN12C and 786-O cells was investi-gated in vivo by using a tumor model. Results:The average time of sphere formation in SFM was shorter in SN12C than in 786-O (5 days vs. 7 days). Moreover, the expression levels of CD133, CD44, Nanog, and Oct3/4 in SN12C and 786-O significantly differed (P<0.05). When transplanted in nude mice, 786-O spheres were less tumorigenic than SN12C spheres. Conclusion:SN12C spheres possess the main defining characteristics of renal cancer stem cell;thus, SN12C is the more suitable cell line to be used to isolate cancer stem cells compared with 786-O.
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Objective:To discuss the influence of ALDH1+and CD133+phenotypic breast cancer stem-like cells in TA2 triple negative breast cancer on promoting epithelial-mesenchymal transition (EMT) occurrence in TA2 mice with triple-negative breast cancer and on their biological behavior. Methods:Flow cytometry was performed to analyze the markers ALDH1 and CD133 in TA2 mice triple nega-tive breast cancer and breast cancer stem-like cells with ALDH1+, ALDH1?, CD133+, and CD133?phenotypes, which were sorted out. Then, the TA2 mice were inoculated with sorted tumor cells according to cell type. The mice were divided into ALDH1+, ALDH1?, CD133+, and CD133-groups. The tumor-growing conditions were observed. A tumor tissue was sliced for the immunohistochemical testing of ALDH1?, CD133?, and EMT-related Twist1, E-cadherin, and VE-cadherin proteins. The expression difference of breast cancer stem cell surface markers ALDH1 and CD133 in triple-negative breast cancer and EMT-related proteins Twist1, E-cadherin, and VE-cad-herin was analyzed. Results:The expression rates of breast cancer stem cell markers ALDH1 and CD133 in TA2 mice triple negative breast cancer were 31.2%and 6.5%, respectively. The tumor growth ability of TA2 mice from ALDH1+group was obviously stronger than that from ALDH1?group. The CD133+group was evidently stronger than CD133?group. The immunohistochemical results showed that ALDH1, Twist1, and VE-cadherin expression levels in the ALDH1+group were evidently higher than that in the ALDH1?group (all P<0.05). E-cadherin expression decreased (P<0.05). CD133?, Twist1, and VE-cadherin expression levels in CD133+group were higher than that in CD133?group (all P<0.05). Conclusion:In TA2 mice triple negative breast cancer, ALDH1+and CD133+phenotypic breast cancer stem-like cells may influence the expression of EMT-related proteins, and promote the formation of triple-negative breast cancer.
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Objective:The clinicopathological features, diagnosis, and prognosis of follicular thyroid carcinoma (FTC) with distant me-tastasis as the first manifestation were evaluated in this study. Methods:A total of 129 FTC cases with clinical data were retrospective-ly analyzed in the Department of Pathology, Tianjin Medical University Cancer Institute and Hospital (January 2001 to January 2016). Survival analysis and conjoint analysis on FTC with clinical data, diagnosis, and morphological characteristics with distant metastasis as the first manifestation were performed. Results:Among the 129 FTC cases, 24 cases demonstrated distant metastasis as the first mani-festation (18.6%). Bone metastasis was the most common (13.2%). The presence of mass and pain at the metastatic sites were the usu-al clinical complaints. The morphological characteristics of FTC with distant metastasis can be classified into four subtypes:microfollicu-lar (10 cases), solid (4 cases), normofollicular (9 cases), and macrofollicular (1 case). Immunostaining tests on thyroglobulin and thyroid transcription factor-1 showed positive results in FTC with metastasis. Survival analysis showed that the five-year survival rates in the 24 cases were 87.1%. The prognosis of patients with solitary metastasis was better than that of patients with multiple metastasis (P=0.022). A higher survival rate was found in the normofollicular and macrofollicular subtypes than that detected in the microfollicular and solid subtypes (P=0.012). Conclusion:FTC is susceptible to distant metastasis. Some patients with FTC demonstrated distant me-tastasis as the first manifestation, and their diagnosis can be confirmed by pathological feature analysis and immunostaining. The prog-nostic significance is possibly related to the number of lesions of FTC with distant metastasis and histopathological subtypes.
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Objective To explore whether hypoxia could promote epithelial-mesenchymal transition (EMT) in various differentiated colorectal cancer cells, and analyse the effect of hypoxia on invasion and migration of colorectal cancer cells. Methods HCT116 (poorly differentiated) and HT-29 (highly differentiated) colorectal adenocarcinoma cells were selected respectively. The morphological changes of two cell lines were observed after 0,10,25,50,100 and 150 mg/L cobalt chloride (CoCl2) treatment for 48 h. The expression of hypoxia-inducible factor-1α(HIF-1α) protein was analysed after 0, 10,25,50,100 and 150 mg/L CoCl2 treatment for 48 h. An optimal concentration of CoCl2 was then selected. Methylthiazolyl tetrazolium (MTT) assay was used to detect the proliferation of two kinds of colorectal cancer cells induced by CoCl 2 at different time points (0, 24, 48, 72 and 96 h), and to select an optimal time. Under the optimal concentration and time conditions, the HCT116 and HT-29 cells were processed by hypoxia (hypoxia group) and normoxia (normoxic group). Transwell invasion assay and Wound healing assay were used to detect cell invasion and migration in two groups. Western blot assay and RT-PCR were used to detect protein and mRNA expression levels of HIF-1α, E-cadherin and Vimentin in two groups. Results Two kinds of cells showed obvious morphological changes after 50 mg/L CoCl2 treatment for 48 h. HIF-1αprotein level first increased and then decreased in two groups of cells with the increased concentration of CoCl 2, and 50 mg/L CoCl2 was the optimal concentration (P<0.05). The cell proliferation showed a tendency to decrease after the increase in both kinds of cells with or without hypoxia for 0-96 h (P<0.05), and 48 h was the optimal time. The transmembrane number and cell migration rate were significantly more in hypoxia group than those of normoxic group (P<0.05). The protein and mRNA levels of HIF-1α and Vimentin were significantly higher in hypoxia group than those of normoxic group in HCT116 and HT-29 cell lines (P<0.05). E-cadherin protein and mRNA levels were significantly lower in hypoxia group than those of normoxic group (P<0.05). Conclusion Hypoxia can promote EMT in different differentiated colorectal cancer cells, and can enhance invasion and migration of two kinds of colorectal cancer cells.
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Objective:To determine the expression of BMP4 in hepatocellular carcinoma (HCC) and to study the role of BMP4 in inducing epithelial-mesenchymal transition (EMT) to analyze the effect of BMP4 on the migration and invasion of HCC cells. Methods: The expression of BMP4 in HCC specimens was examined by immunohistochemistry staining, and the correlations were analyzed between the expression of BMP4 and clinicopathological data. The BMP4 expression plasmid was transfected into HepG2 cells to induce exogenous overexpression of BMP4 protein. The changes of HepG2 cell morphology were detected after BMP4 transfection by using a microscope; the changes of the expression of BMP4, EMT-related protein (E-cadherin, Vimentin) in HepG2 cells were detected by Western blot after transfection of BMP4;the wound healing assay in vitro was used to detect the effects of BMP4 gene transfection on the ability of migration of HepG2 cells;the invasion assay was used to determine the role of transfection of BMP4 on the invasive potential of HepG2 cells. Results: Immunohistochemistry staining method displayed that BMP4 expression was positively associated with age, histological differentiation, stage, and poor prognosis. After BMP4 overexpression, the morphology of HepG2 cells showed significant changes from a paving stone structure with cell-cell adhesion to a fibroblastic shape, which showed typical EMT change; Western blot exhibited that the expression of E-cadherin was downregulated and the Vimentin expression was upregulated in HepG2 cells;the wound healing and invasion assay showed that the migration and invasion potentials of HepG2 cells were significantly enhanced. Conclusion: BMP4, which displayed a high expression in HCC specimens, was closely associated with clinicopathologic data, and BMP4 may promote migration and invasion of HCC cells by inducing epithelial-mesenchymal transition.
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Objective:To investigate the inhibitory effect of Dickkopf-1 (Dkk1) on vasculogenic mimicry (VM) formation and the relevant mechanism. Methods:CD34-PAS dual staining and immunohistochemical staining were used to detect and analyze the re-lationship between VM existence and Dkk1 expression in 217 human colon cancer tissue samples;three dimensional (3D) culture was used to detect the influence of Dkk1 on tube structure formation and on VE-cadherin expression;a subcutaneous mouse xenograft mod-el was made to further validate the inhibitory role of Dkk1 on VM formation in vivo. Results:VM-positive samples indicated a lower expression of Dkk1(P<0.05);colon cancer cells with Dkk1 overexpression exhibited a decreased ability to form tube-like structure and a decreased expression of VE-cadherin;Dkk1 inhibited the VM-formation abilities of human colorectal carcinoma cell line xenograft tu-mor tissue. Conclusion:Dkk1 inhibits the VM formation of colon cancer.
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Objective:To investigate the clinical significance of epithelial-to-mesenchymal (EMT) in lung squamous cell carcino-ma (LSCC) and to examine the effect of EMT on the invasive and migration abilities of LSCC. Methods:Immunohistochemical stain-ing was performed to determine the expression of E-cadherin, Vimentin, and TGF-β1 in 79 LSCC patients, and the clinical significance was explored. SK-MES-1 lung squamous carcinoma cells were cultured in conditioned medium containing various concentrations of transforming growth factor-β1 (TGF-β1) for 5 and 10 days. The expression levels of E-cadherin and Vimentin were detected via West-ern blot and reverse transcription-polymerase chain reaction (RT-PCR). With different concentrations and induction times, invasion and wound healing assays were performed to evaluate the invasion and migration abilities. Results:E-cadherin expression was significantly lower, whereas Vimentin expression was significantly higher in LSCC with lymph node metastasis than in that without noda metastasis (P<0.05). In the tissues of 79 LSCC patients, TGF-β1 expression was significantly related to lymph node metastasis (P<0.05). Western blot showed that Vimentin expression was higher, whereas E-cadherin expression was lower in TGF-β1 inducing medium with 10 ng/mL SK-MES-1 cells than in the other media. RT-PCR showed similar results. Scratch test and invasion assay both showed that treat-ment of cells with cytokines markedly enhanced the migration and invasion of the cells. Conclusion:Lymph node metastasis of LSCC correlates with EMT. SK-MES-1 cells undergo EMT via TGF-β1 induction, which enhances invasion and migration.
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Objective To investigate the effects of interferon-gamma (IFN-γ) on migration,invasion and vasculogenic mimicry (VM) formation of human melanoma cell line MUM-2B. Methods MUM-2B cells were divided into three groups, control group (10%FBS in DMEM), treatment group1 (10μg/L IFN-γ) and treatment group2 (100μg/L IFN-γ). Different concentrations of IFN-γ were added in the culture medium of MUM-2B cells. Wound-healing assay and matrigel invasion assay were performed to examine the migration and invasion ability of MUM-2B cells. Three-D culture was used to observe the VM formation. The expression of vascular endothelial growth factor (VEGF) of MUM-2B cells was detected by Western blot assay. Results The result of wound-healing assay showed that the migration distance of cells was decreased in treatment groups compared with that of control group. The migration distance of cells was decreased in treatment group 2 compared with that of treatment group 1(P＜0.05). The result of matrigel invasion assay showed that the number of invaded cells was decreased in treatment groups compared with that of control group, and which was significantly decreased in treatment group2 than that of treatment group1 (P＜0.05). The result of 3-D culture showed that cells in control group can form typical VM tube-like structures, whereas cells in treatment groups cannot. Western blot assay showed that the expression of VEGF protein was significantly decreased in treatment groups compared with that of control group, and the expression of VEGF protein was significantly decreased in treatment group2 than that of treatment group 1(P＜0.05). Conclusion These data suggest that IFN-γinhibits migration and invasion of MUM-2B cells, and inhibits VM formation by down regulating VEGF expression in vitro.
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Given the unlimited proliferation and aerobic glycolysis in tumor cells, these cells require more glucose, glutamine, and other nutrients compared with normal cells. Tumor cells are often affected by insufficient nutrient supply. However, by sensing changes in the nutrient supply in tumor microenvironment and by regulating signal-transduction pathways, some specific proteins can help tumor cells in blocking the cell cycle, reprogramming metabolism, and regulating autophagy to progress and survive against nutri-ent stress. Exciting innovations have been made to elucidate the mechanisms relevant to this process. This review aims to highlight re-cent studies on the mechanisms of sensing the low nutrient supply in microenvironments, as well as the downstream effect factors in cancer cells.
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Objective:To analyze the clinico-pathological characteristics, pathological diagnosis, and treatment of rhabdoid tu-mor. Methods:The medical records of four rhabdoid tumor patients that were admitted to the Tianjin Medical University Cancer Insti-tute and Hospital since 2000 were analyzed based on existing literature. Results:In one of the four cases, the tumor originated from the kidney, whereas in the other three, the tumor occurred from extra-renal soft tissues. Histologic analysis revealed that the tumor cells were loosely arranged with diffuse growth, vesicular nuclei, dyed cytoplasm, visible eosinophilic inclusions, and more nuclear fission. The results of immunohistochemical staining showed that the vimentin and epithelial membrane antigen were positive, whereas CK, CD99, CD34, and S-100 were positive at different degrees. MyoD1, Desmin, and INI-1 were negative. Conclusion:Rhabdoid tumor is rare and highly aggressive. It occurs mainly in the kidney and can also be found in other systems. The unique pathological form and im-munohistochemical staining observed on the tumor can be used as reference for diagnosis.
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Objective:To investigate the correlations of Lauren classification and world health organization (WHO) classification of gastric cancer (GC) with microvascular density (MVD), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 1 (VEGFR1), vascular endothelial growth factor receptor 2 (VEGFR2), and p53. Methods:The clinical data of 89 patients with GC were collected. The collected specimens were categorized on the basis of Lauren classification and WHO classification. CD34/periodic acid-Schiff (PAS) double staining was performed to validate MVD. Immunohistochemistry was conducted to investigate the expression levels of MMP-2, MMP-9, VEGF, VEGFR1, VEGFR2, and p53. Results:MVD was not correlated with Lauren classification or WHO classification (P>0.05). Lauren typing was associated with the expression levels of MMP-9, VEGFR1, and p53 (P0.05). Cox proportional hazards model revealed that Lauren classification and WHO classification were the prognostic factors of overall survival (P<0.05). Conclusion:This research on tumor related factors, angiogenesis, and different classifications of GC may provide new methods to treat this disease.
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Objective:This study aims to investigate the potential of colon cancer cells to differentiate into vascular endothelial cells in endothelial-induced specific environment. Methods:Three colon cancer cells with different differentiated level HCT116 (poor-ly differentiated), SW480 (moderately differentiated), HT29 (well differentiated) were cultured in the conditioned medium containing the endothelial-inducing factors for 15 days respectively. The expression of vascular endothelial indicators Platelet endothelial cell adhe-sion molecule-1、Endothelial cell adhesion molecule CD34 was detected via western blot. Immunofluorescence staining was performed to examine CD31 and CD34 expression level in HCT116 after cultured in endothelial-inducing medium and ordinary medium for 15 days respectively, and the three-dimensional (3D) culture was used to detect the abililty of in vitro tube-like structure formation. Re-sults:Western blot showed that CD31 and CD34 expression level were negatively correlated with degree of differentiation in colon can-cer cells. CD31 and CD34 expression in endothelial-inducing medium HCT116 cells (poorly differentiated) were higher then in the nor-mal medium, while the CD31 and CD34 expression in SW480 cells (moderately differentiated) and HT29 cells (well differentiated) in the two cultural mediums were not notably changed. Immunofluorescence staining illustrated that CD31 and CD34 expression in HCT116 cells cultured in endothelial-inducing medium increased compared with those cultured in ordinary medium. In vitro three-di-mensional culture demonstrated that ability of tube-like structure formation was notably enhanced after endothelial-inducing cultured. Conclusion:Endothelial-inducing medium could promote colon cancer cells with strong stemness differentiate toward vascular endo-thelial cells.
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Neovascularization is the fundamental process during tumorigenesis and tumor malignant progression. According the traditional neovascularization theory, tumor vasculatures are mainly developed through angiogenesis by sprouting from preexisting ves-sels and vasculogenesis via recruitment of endothelial progenitor cells from the bone marrow, and the endothelial-dependant vessels are the only way that provides tumor with blood. However, more and more studies indicate that tumor microcirculation network is heteroge-neous and cancer stem cells (CSCs) play an important role during tumor neovascularization. This review highlights the contribution of CSCs to tumor microcirculation modes and the potential anti-angiogenesis targets. Furthermore, this review presents insights for perti-nent studies in the future.
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Tissue factor pathway inhibitor-2 (TFPI-2), a member of the Kunitz-type family, is a broad-spectrum serine proteinase inhibitor. The expression of TFPI-2 is inversely related to increasing degree of malignancy, suggesting a role of TFPI-2 in the mainte-nance of tumor stability and inhibition of the growth of neoplasma. Aberrant methylation of TFPI-2 promoter cytosine-phosphorothio-ate-guanine (CpG) islands has been widely documented to be responsible for diminished expression of TFPI-2 mRNA and protein dur-ing cancer progression. TFPI-2 expression is significantly up-regulated by the ERK1/2 and JNK signaling pathways and modestly in-creased by VEGF, TNF-alpha, and fibroblast growth factor in time-and dose-dependent manners. TFPI-2 can maintain the stability of the tumor environment and inhibit invasiveness and growth of neoplasms. TFPI-2 has also been shown to regulate proliferation, apopto-sis, and vasculogenic mimicry of tumor cells, which may contribute significantly to tumor growth inhibition. Restoration of TFPI-2 ex-pression in tumor tissue inhibits tumor growth and metastasis, which creates a novel possibility of cancer patient treatment. This review focuses on the expression and the molecular regulation mechanisms of TFPI-2 in malignant tumors that control the functions of TFPI-2 in proliferation, apoptosis, and angiogenesis. Insight into these processes will improve our understanding of TFPI-2 and provide new ap-proaches for rational treatment strategies.
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<p><b>OBJECTIVE</b>To explore the expression of Bcl-2 mRNA and its effect on prognosis of patients with primary gastrointestinal diffuse large B-cell lymphoma (PGI-DLBCL).</p><p><b>METHODS</b>Real time quantitative PCR was used to determine the expression of Bcl-2 mRNA in 40 PGI-DLBCL patients and 17 healthy controls. The association of Bcl-2 expression with clinicopathological features and prognosis of the patients was analyzed.</p><p><b>RESULTS</b>The expression level of Bcl-2 mRNA in PGI-DLBCL patients was 1.03 ± 0.93, significantly higher than that of the controls (0.41 ± 0.21) (P < 0.05). The expression of Bcl-2 mRNA in stage IIE-IV patients (1.28 ± 1.01) was significantly higher than that in the stage I-II2 patients (0.62 ± 0.61) (P < 0.05). The expression of Bcl-2 mRNA in patients with international prognostic index (IPI) score >2 (1.95 ± 1.27) was significantly higher than those with IPI score ≤ 2 (0.86 ± 0.75)(P < 0.05). The expression of Bcl-2 mRNA in patients with complete remission (CR) (0.71 ± 0.58) was significantly lower vs. 2.42 ± 0.91 in patients with no CR (P < 0.05). Univariate analysis indicated that β2-MG, IPI score>2, the Lugano staging, and Bcl-2 mRNA expression were associated with overall survival (OS) and progression-free survival (PFS) (P < 0.05). Multivariate analysis indicated that IPI score>2 was independently associated with OS (P < 0.05), and both IPI score >2 and Bcl-2 mRNA expression were independently associated with PFS (P < 0.05).</p><p><b>CONCLUSIONS</b>The expression of Bcl-2 mRNA in the tumor tissue of PGI-DLBCL patients is significantly higher than that in controls. PGI-DLBCL patients with higher expression of Bcl-2 have a poor chemotherapy response and inferior prognosis. IPI score >2 and higher expression of Bcl-2 mRNA are independent poor prognostic factors for PFS in PGI-DLBCL patients.</p>