Expression of Coiled-Coil Domain Containing Family mRNA and prognostic value in hepatocellular carcinoma

Abstract Background: The CCDC family plays a significant role in the development and progression of malignant tumors. However, the relationship between CCDC family members and HCC progression is incompletely known. This study used bioinformatics analysis to investigate the expression as well as clinical prognostic value of CCDC family members in HCC and to predict the role of CCDCs family in the development and progression of HCC. Methods: This study utilized the data from two platforms databases to explore the diagnostic value and prognostic significance of CCDC family members by Cox proportional hazards regression analysis, Kaplan-Meier curve and log-rank test, ROC and nomogram diagnostic and prognostic analysis methods. GSEA and tumor microenvironment analysis were employed to investigate the underlying mechanisms and cell-cell interactions of CCDCs family in the development and progression of HCC. The relationship between mutational signatures and CCDCs family were evaluated in HCC patients with somatic mutation. Results: Five CCDC family members (CCDC34, CCDC137, CCDC77, CCDC93 and CCDC21) mRNA expression showed significantly higher in HCC tissues than in normal tissues and high expression levels of these genes predicted poor prognosis in HCC patients. The combined effect analysis of five CCDCs family prognostic markers suggests that the prognosis difference for CCDC family members combination was more significant than that for any individual CCDC family genes. We then developed a risk score model that could predict the prognosis of HCC, and nomogram gene expression was visualized with the probability of predicting the prognosis of HCC by clinical factors. GSEA revealed that, while five CCDCs family combined high expression was associated with increased cell cycle progression and low expression was associated with complement activation pathway. Mutation analysis showed that the combined high expression group had a higher TP53 mutation rate than the combined low expression group, and the high expression group showed higher TMB, which was associated with a better prognosis than high TMB. Conclusions: Our data suggest that the expression of CCDC34, CCDC137, CCDC77, CCDC93 and CCDC21 may be potential prognostic markers in HCC and in combination have a strong interaction and better predictive value for HCC prognosis.

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Prognostic significance of esterase gene expression in multiple myeloma

British Journal of Cancer ◽

10.1038/s41416-020-01237-1 ◽

2021 ◽

Author(s):

Romika Kumari ◽

Muntasir Mamun Majumder ◽

Juha Lievonen ◽

Raija Silvennoinen ◽

Pekka Anttila ◽

...

Keyword(s):

Gene Expression ◽

Multiple Myeloma ◽

Bone Marrow ◽

Prognostic Markers ◽

Prognostic Significance ◽

Genomic Variation ◽

High Expression ◽

Genetic Profile ◽

Esterase Gene ◽

Low Expression

Abstract Background Esterase enzymes differ in substrate specificity and biological function and may display dysregulated expression in cancer. This study evaluated the biological significance of esterase expression in multiple myeloma (MM). Methods For gene expression profiling and evaluation of genomic variants in the Institute for Molecular Medicine Finland (FIMM) cohort, bone marrow aspirates were obtained from patients with newly diagnosed MM (NDMM) or relapsed/refractory MM (RRMM). CD138+ plasma cells were enriched and used for RNA sequencing and analysis, and to evaluate genomic variation. The Multiple Myeloma Research Foundation (MMRF) Relating Clinical Outcomes in MM to Personal Assessment of Genetic Profile (CoMMpass) dataset was used for validation of the findings from FIMM. Results MM patients (NDMM, n = 56; RRMM, n = 78) provided 171 bone marrow aspirates (NDMM, n = 56; RRMM, n = 115). Specific esterases exhibited relatively high or low expression in MM, and expression of specific esterases (UCHL5, SIAE, ESD, PAFAH1B3, PNPLA4 and PON1) was significantly altered on progression from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, SIAE and USP4, and low expression of PCED1B, were identified as poor prognostic markers (P < 0.05). The MMRF CoMMpass dataset provided validation that higher expression of PAFAH1B3 and SIAE, and lower expression of PCED1B, were associated with poor prognosis. Conclusions Esterase gene expression levels change as patients progress from NDMM to RRMM. High expression of OVCA2, PAFAH1B3, USP4 and SIAE, and low expression of PCED1B, are poor prognostic markers in MM, suggesting a role for these esterases in myeloma biology.

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ERCC1 expression and platinum chemosensitivity in patients with ovarian cancer: A meta-analysis

The International Journal of Biological Markers ◽

10.1177/1724600820963396 ◽

2020 ◽

Vol 35 (4) ◽

pp. 12-19

Author(s):

Chunjie Zhang ◽

Shan Gao ◽

Jingwen Hou

Keyword(s):

Ovarian Cancer ◽

Excision Repair ◽

Meta Analysis ◽

Effective Rate ◽

High Expression ◽

High Expression Group ◽

Significant Difference ◽

Ercc1 Expression ◽

The Relationship ◽

Low Expression

Objective: This study aimed to comprehensively investigate the correlation of ERCC1 expression and chemosensitivity of ovarian cancer. Methods: The literature on the relationship between the excision repair cross complementary gene 1 (ERCC1) and the chemosensitivity of ovarian cancer published in PubMed, Web of Science, EMBASE, CNKI, and the China Wanfang database from the establishment of the databases to June 2020 were searched. Chemosensitivity is evaluated by clinical effective rate (complete remission plus partial remission). Statistical analysis was carried out by using Stata 15.1 software. Results: A total of 11 articles met the inclusion criteria, consisting of 758 patients with ovarian cancer. The results showed a significant difference in chemosensitivity between the low expression group and the high expression group of ERCC1 (odds ratio 4.23; 95% confidence interval 2.96, 6.06; P < 0. 01). The same result was shown in the ethnicity subgroup. Conclusion: The chemosensitivity of ovarian cancer patients with a low expression of ERCC1 is better than that of patients with a high expression.

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Impact of CKLF-like MARVEL Transmembrane Domain Containing 6 (CMTM6) Expression in Gastric Cancer

10.21203/rs.3.rs-48504/v1 ◽

2020 ◽

Author(s):

M Nishi ◽

Mitsuo Shimada ◽

Kozo Yoshikawa ◽

Jun Higashijima ◽

Takuya Tokunaga ◽

...

Keyword(s):

Gastric Cancer ◽

Transmembrane Domain ◽

Disease Free Survival ◽

University Hospital ◽

High Expression ◽

High Expression Group ◽

Group 5 ◽

Relationship Of ◽

The Relationship ◽

Low Expression

Abstract Background: CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is the master regulator of programmed cell death-ligand 1(PD-L1). We aimed to clarify the significance of CMTM6 expression in gastric cancer (GC). Methods: A total of 105 patients who had undergone curative surgical resection for stage II/III GC at Tokushima University Hospital were included in this study. The expression of CMTM and PD-L1 was examined by immunohistochemistry. Additionally, the relationship of each expression level to several prognostic factors was examined using univariate and multivariate analyses. Results: CMTM6 was not positively correlated with any of the factors examined. The overall survival (OS) rates were significantly poorer in the CMTM6 high-expression group than in the CMTM low-expression group (5-year OS: 57.2% vs. 79.2%, respectively; p<0.05). Disease-free survival (DFS) was significantly poorer in the CMTM high-expression group than in the CMTM6 low-expression group (5-year DFS: 52.8% vs. 72.4%, respectively; p=0.20). Multivariate analysis confirmed CMTM6 expression as an independent prognostic factor in DFS (p<0.05). CMTM6 expression tended to be correlated with PD-L1 expression (p=0.07), and PD-L1 expression was positively correlated with PD-1 expression (p<0.05).Conclusions: CMTM6 is associated with a poor prognosis and immunotolerance through PD-L1 in GC.

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Expression and Clinical Significance of Long Non-Coding RNA RP4-669H2.1 in Glioblastoma

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2645 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1073-1077

Author(s):

Xinhu Sun ◽

Jingyu Zhou ◽

Xijuan Wu ◽

Yongpeng Yu ◽

Xia Zhan ◽

...

Keyword(s):

Multivariate Analysis ◽

Dna Binding ◽

Poor Prognosis ◽

Prognostic Value ◽

Target Genes ◽

Tnm Stage ◽

High Expression ◽

Biological Functions ◽

High Expression Group ◽

Low Expression

Neuroglioma is the most common malignant tumor in the central nervous system and still has a poor prognosis. Here, we investigated the prognostic value of long non-coding RNAs(lncRNAs) in glioblastoma. We first analyzed the lncRNA expression profiles of glioblastoma (GBM) in The Cancer Genome Atlas database and selected the most differential survival genes (lncRNA RP4-669H2.1) for further validation. We then performed qRT-PCR using samples of 88 glioblastoma patients treated in our department between January 2011 and December 2017 that were retrospectively selected to validate the prognostic value of RP4-669H2.1expression in glioblastoma. Using a Cox multivariate analysis, we explored the prognostic value of RP4-669H2.1 and analyzed whether it was an independent prognostic factor. This analysis confirmed that the RP4-669H2.1 expression was significantly associated with glioblastoma-associated mortality in this patient cohort (P =1.80E–05) in TCGA database. In fact, the overall survival (OS) of the RP4-669H2.1 high-expression group (78 cases) was lower than that of the low-expression group (49 cases) (P = 4.6E–06) in TCGA database. Moreover, the TNM stage of the RP4-669H2.1 high-expression group was higher than that of the RP4-669H2.1 low-expression group (P = 0.001). A multivariate analysis further showed that a higher TNM stage (OR = 2.167, 95% CI: 1.349–3.479) and a higher RP4-669H2.1 expression (OR = 2.933, 95% CI: 1.122–7.663) were independent risk factors for the OS of glioblastoma patients. Finally, we predicted the target genes of RP4-669H2.1 using a Multi Experiment Matrix and annotated their biological functions. We observed that the target genes of RP4-669H2.1 were mainly enriched in biological functions related to DNA-binding transcription factor activity. Among these, we selected SMAD6 because the expression of RP4-669H2.1 was positively correlated with that of SMAD6 in glioblastoma. Overall, we conclude that the upregulation of RP4-669H2.1 is an independent poor prognosis factor for glioblastoma and that it can regulate the DNA-binding activity of transcription factors.

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Evaluation of the Therapeutic Effect of Adjuvant Transcatheter Arterial Chemoembolization Based on Ki67 After Hepatocellular Carcinoma Surgery

Frontiers in Oncology ◽

10.3389/fonc.2021.605234 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yu-Fei Zhao ◽

Xiu Xiong ◽

Kai Chen ◽

Wei Tang ◽

Xu Yang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transcatheter Arterial Chemoembolization ◽

Tumor Resection ◽

High Expression ◽

Ki67 Expression ◽

High Expression Group ◽

Significant Difference ◽

The Relationship ◽

Low Expression ◽

Arterial Chemoembolization

Background and aimsThis study aimed to determine the relationship between Ki67 expression and the efficacy of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) in patients with hepatocellular carcinoma.MethodsThe Kaplan-Meier method was used to analyze the recurrence-free survival (RFS) and overall survival (OS) rates between the sub-groups in the ki67 low expression group and the ki67 high expression group and analyze the relationship between the expression of Ki67 and the efficacy of TACE.ResultsAfter PSM, there was no significant difference in the RFS and OS between the surgery + TACE and surgery subgroups after 1, 2, or 3 years (RFS: 63.9%, 55.6%, and 42.9% vs. 83.3%, 63.9%, and 55.6%, respectively, P = 0.279; OS: 91.7%, 83.3%, and 74.3% vs. 91.7%, 88.9%, and 71.4%, respectively, P = 0.890) in the Ki67 low-expression group. The RFS and OS were higher in the surgery + TACE subgroup than the surgery subgroup after 1, 2, and 3 years (RFS: 80.0%, 77.5%, and 69.2% vs. 53.5%, 39.5%, and 32.6%, respectively, P<0.001; OS: 97.5%, 85.0%, and 79.5% vs. 79.1%, 48.8%, and 42.9%, respectively, P = 0.001) in the Ki67 high expression group. The RFS was higher in the Ki67 high-expression subgroup than the low-expression subgroup after 1, 2, and 3 years, and OS had no significant difference (RFS: 80.0%, 79.5%, and 69.2% vs. 67.4%, 56.5%, and 46.7%, respectively, P = 0.035; OS: 97.5%, 85.0%, and 79.5% vs. 93.5%, 82.6%, and 75.6%, respectively, P = 0.665) in the surgery + TACE group.ConclusionsFor patients with hepatocellular carcinoma and high expression of Ki67 (Ki67≥20%), adjuvant hepatic artery chemoembolization after radical liver tumor resection effectively reduced the probability of tumor recurrence after surgery and prolonged the OS of patients. High Ki67 expression during the post-operative follow-up evaluation of hepatocellular carcinoma patients is an indicator for adjuvant TACE therapy.

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Expression and clinical significance of CMTM1 in hepatocellular carcinoma

Open Medicine ◽

10.1515/med-2021-0221 ◽

2021 ◽

Vol 16 (1) ◽

pp. 217-223

Author(s):

Xin Song ◽

Shidong Zhang ◽

Run Tian ◽

Chuanjun Zheng ◽

Yuge Xu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transmembrane Domain ◽

Disease Free Survival ◽

Clinicopathological Characteristics ◽

The Cancer Genome Atlas ◽

High Expression ◽

Chi Square ◽

Tumor Tissues ◽

The Relationship ◽

Low Expression

Abstract Background CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. Methods The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan–Meier model. Results Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients (P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group (P < 0.05). Conclusion CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.

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The relationship between CD204 M2-polarized tumour-associated macrophages (TAMs), tumour-infiltrating lymphocytes (TILs), and microglial activation in glioblastoma microenvironment: a novel immune checkpoint receptor target

Discover Oncology ◽

10.1007/s12672-021-00423-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Maher Kurdi ◽

Badrah Alghamdi ◽

Nadeem Shafique Butt ◽

Saleh Baeesa

Keyword(s):

Microglial Activation ◽

Inverse Correlation ◽

Idh1 Mutation ◽

High Expression ◽

Kaplan Meier ◽

Significant Difference ◽

Tumour Infiltrating Lymphocytes ◽

Infiltrating Lymphocytes ◽

The Relationship ◽

Low Expression

Abstract Background Tumour associated macrophages (TAMs) and tumour infiltrating lymphocytes (TILs) are considered dominant cells in glioblastoma microenvironment. Aim The purpose of this study was to assess the expression of CD204+ M2-polarized TAMs in glioblastomas and their relationship with CD4+TILs, Iba+microglia, and IDH1 mutation. We also exploreed the prognostic value of these markers on the recurrence-free interval (RFI). Methods The expressions of CD204+TAMs, CD4+TILs, and Iba1+microglia were quantitively assessed in 45 glioblastomas using immunohistochemistry. Kaplan–Meier analysis and Cox hazards were used to examine the relationship between these factors. Results CD204+TAMs were highly expressed in 32 tumours (71%) and the remaining 13 tumours (29%) had reduced expression. CD4+TILs were highly expressed in 10 cases (22%) and 35 cases (77.8%) had low expression. There was an inverse correlation between CD204+TAMs and CD4+TILs, in which 85% of tumours had a high expression of CD204+TAMs and a low expression of CD4+TILs. Nevertheless, there was no significant difference in IDH1 mutation status between the two groups (p = 0.779). There was a significant difference in Iba1+microglial activation between IDH1mutant and IDH1wildtype groups (p = 0.031). For cases with a high expression of CD204+TAMs and a low expression of CD4+TILs, there was a significant difference in RFI after treatment with chemoradiotherapy or radiotherapy (p = 0.030). Conclusion Glioblastoma with a dense CD204+TAMs and few CD4+TILs is associated with IDH1wildtype. These findings suggest that TAMs masks tumour cell and suppress T-cell tumoricidal functions via immunomodulatory mechanisms. Blockade of the CD204-TAM receptor may prevent this mechanism and allow the evolution of TILs.

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Clinicopathological and Prognostic Significance of CBX3 Expression in Human Cancer: a Systematic Review and Meta-analysis

Disease Markers ◽

10.1155/2020/2412741 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Hexin Lin ◽

Xin Zhao ◽

Lu Xia ◽

Jiabian Lian ◽

Jun You

Keyword(s):

Malignant Tumors ◽

Human Cancer ◽

Meta Analysis ◽

Univariate Analysis ◽

Prognostic Significance ◽

Cancer Prognosis ◽

High Expression ◽

Clinicopathological Parameters ◽

Malignant Neoplasms ◽

Tumor Type

Background. Chromebox protein homolog 3 (CBX3) as a member of the heterochromatin-associated protein 1 (HP1) family has been reported to be overexpressed in human cancer tissues. Numerous studies have shown the relationship between the CBX3 expression and clinicopathological factor or prognosis in malignant tumors, but their results are inconsistent. To address these results, a meta-analysis was described to investigate the prognostic value and clinicopathological significance of CBX3 expression in human malignant neoplasms. Methods. PubMed, Web of Science, Embase, and Chinese National Knowledge Infrastructure (CNKI) were used to search eligible literatures, including publications prior to September 2019. The role of CBX3 in cancer prognosis and clinicopathological characteristics was assessed by pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs). Results. Eleven studies with 1682 cancer patients were enrolled in this meta-analysis. This analysis demonstrated that the patients’ increased CBX3 expression was significantly associated with poor overall survival (OS) (univariate analysis: HR = 1.81 , 95% CI 1.46-2.25; multivariate analysis: HR = 1.95 , 95% CI 1.63-2.34). Subgroups analysis by tumor type also indicated that high expression of CBX3 was correlated with poor OS in tongue squamous cell carcinoma ( HR = 3.31 , 95% CI 2.03-5.39), lung cancer ( HR = 1.66 , 95% CI 1.21-2.29), genitourinary cancer ( HR = 2.03 , 95% CI 1.15-3.58), and digestive cancer ( HR = 1.48 , 95% CI 1.23-1.79). For clinicopathological features, high expression of CBX3 was associated with lymph node metastasis ( OR = 2.96 , 95% CI 1.42-6.20) and lager tumor size ( OR = 1.60 , 95% CI 1.12-2.28). Conclusion. The results of this meta-analysis indicated that CBX3 expression may be a novel biomarker for predicting patient prognosis and clinicopathological parameters in multiple human cancer.

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Prognostic significance of MUC2, CDX2 and SOX2 in stage II colorectal cancer patients

BMC Cancer ◽

10.1186/s12885-021-08070-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sara Ribeirinho-Soares ◽

Diana Pádua ◽

Ana Luísa Amaral ◽

Elvia Valentini ◽

Daniela Azevedo ◽

...

Keyword(s):

Colorectal Cancer ◽

Adjuvant Chemotherapy ◽

Prognostic Significance ◽

Tumor Resection ◽

Disease Free Survival ◽

Predictive Biomarkers ◽

Stage Ii ◽

Health Concern ◽

Rank Test ◽

Low Expression

Abstract Background Colorectal cancer (CRC) remains a serious health concern worldwide. Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRC patients subjected to tumor resection with curative intent, develop disease relapse. Moreover, the therapeutic strategy adopted after surgery is not consensual for these patients. This supports the imperative need to find new prognostic and predictive biomarkers for stage II CRC. Methods For this purpose, we used a one-hospital series of 227 stage II CRC patient samples to assess the biomarker potential of the immunohistochemical expression of MUC2 mucin and CDX2 and SOX2 transcription factors. The Kaplan-Meier method was used to generate disease-free survival curves that were compared using the log-rank test, in order to determine prognosis of cases with different expression of these proteins, different mismatch repair (MMR) status and administration or not of adjuvant chemotherapy. Results In this stage II CRC series, none of the studied biomarkers showed prognostic value for patient outcome. However low expression of MUC2, in cases with high expression of CDX2, absence of SOX2 or MMR-proficiency, conferred a significantly worst prognosis. Moreover, cases with low expression of MUC2 showed a significantly clear benefit from treatment with adjuvant chemotherapy. Conclusion In conclusion, we observe that patients with stage II CRC with low expression of MUC2 in the tumor respond better when treated with adjuvant chemotherapy. This observation supports that MUC2 is involved in resistance to fluorouracil-based adjuvant chemotherapy and might be a promising future predictive biomarker in stage II CRC patients.

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Action of SDF-1/CXCR4 axis in liver metastasis of colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.530 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 530-530 ◽

Cited By ~ 3

Author(s):

Shinichiro Yamada ◽

Mitsuo Shimada ◽

Toru Utsunomiya ◽

Satoru Imura ◽

Yuji Morine ◽

...

Keyword(s):

Liver Metastasis ◽

Colorectal Liver Metastasis ◽

Normal Liver ◽

High Expression ◽

Expression Level ◽

Expression Levels ◽

High Expression Group ◽

Cxcr4 Axis ◽

Low Expression ◽

Liver Tissues

530 Background: It has recently been suggested that the SDF-1/CXCR4 axis is involved in tumor progression, angiogenesis, metastasis, and survival in various cancer. In this study, we investigate the possible role of SDF-1/CXCR4 axis in colorectal liver metastasis. Methods: Both primary colorectal tumors and liver metastatic tumors were obtained from 12 patients with colorectal liver metastasis. Expression levels of CXCR4 and SDF-1 were determined using RT-PCR. In 4 patients with benign liver disease, the expression level of SDF-1 in normal liver tissues was also determined. We divided the 12 patients into two groups; high expression group (n=6) and low expression group (n=6) according to each expression level of SDF-1 and CXCR4, and compared the clinicopathological factors between the two groups. Results: 1. CXCR4 expression levels in primary tumor: The frequency of the peritoneal dissemination in the CXCR4 high expression group was higher than in the low expression group (p=0.07). Moreover, overall survival rate in the CXCR4 high expression group was significantly lower than that in the low expression group (3 year-survival rate: 67% vs. 100%, p<0.05). 2. CXCR4 in metastatic tumor tissues and SDF-1 in non-tumor liver tissues: The expression level of SDF-1 in non-tumor liver tissues was significantly higher than that in normal liver tissues (p<0.01). A significant correlation between the CXCR4 expression levels in metastatic tumor tissues and SDF-1 expression levels of non-tumor liver tissues (p<0.05). The number of metastatic liver tumors in the SDF-1 high expression group tended to be larger than that in the low expression group (p=0.12). Conclusions: The present data suggest that there is a significant association of the SDF-1/CXCR4 axis with enhanced liver metastasis and poor prognosis of the patients with colorectal liver metastasis. Furthermore, an enhanced expression of SDF-1 in non-tumor liver tissues may have an important role in the formation of liver metastasis.

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