The roles of miR-200c in colon cancer and associated molecular mechanisms

The expression of miR-200c has been widely reported to be elevated in tumor tissues and sera of patients with colorectal cancer (CRC) and has been found to correlate with poor prognosis. However, how miR-200c regulates the apoptosis, survival, invasion, metastasis, and tumor growth in colon cancer cells remains to be fully elucidated. This study seeks to further investigate the role of miR-200c in colon cancer development. The expression of miR-200c in tumor and peritumoral tissues of 101 colon cancer patients was measured by real-time PCR. miR-200c expression in HCT-116 and HT-29 colon cancer cells was silenced by adenovirus-carried expression of antisense mRNA against miR-200c. The protein levels of PTEN, p53 Ser¹⁵, PP1, and activated caspase-3 in HCT-116 and HT-29 cells were measured by Western blot. This study demonstrated that the expression of miR-200c was significantly higher in tumor tissues than in peritumoral tissues of colon cancer patients. The elevated miR-200c expression significantly correlated with the TNM stage, lymph node metastasis, and invasion of colon cancer. Silencing miR-200c expression significantly induced cell apoptosis, inhibited long-term survival, invasion, and metastasis, and delayed xenograft tumor growth. Importantly, silencing miR-200c expression sensitized the therapeutic effect of Ara-C (Cytarabine). The effects of silencing miR-200c expression were associated with upregulation of PTEN protein and p53 Ser¹⁵ phosphorylation levels in HCT-116 cells and PTEN protein expression in HT-29 cells. In conclusion, miR-200c functions as an oncogene in colon cancer cells through regulating tumor cell apoptosis, survival, invasion, and metastasis as well as xenograft tumor growth through inhibition of PTEN expression and p53 phosphorylation.     

Proteomics analysis of differential protein expression identifies heat shock protein 47 as a predictive marker for lymph node metastasis in patients with colorectal cancer

The discovery of biomarkers to predict the potential for lymph node (LN) metastasis in patients with colorectal cancer (CRC) is essential for developing improved strategies for treating CRC. In the present study, they used isobaric tags for relative and absolute quantitation to conduct a proteomic analysis designed to identify novel biomarkers for predicting LN metastasis in patients with CRC. They identified 60 differentially expressed proteins specifically associated with LN metastasis in CRC patients and classified the molecular and functional characteristics of these proteins by bioinformatic approaches. A literature search led them to select heat shock protein 47 (HSP47) as the most suitable candidate biomarker for predicting LN metastasis. Validation analysis by immunohistochemistry showed that HSP47 expression in patients with CRC and the number of HSP47‐positive spindle cells in the tumor stroma were significantly higher compared with those in adjacent normal colonic mucosa, and the number of the latter cells increased with tumor progression. Further, the number of HSP47‐positive spindle cells in stroma was a more informative marker for identifying LN metastasis than HSP47expression. Multivariate analysis identified spindle cells that expressed elevated levels of HSP47 as an independent predictive biomarker for CRC with LN metastasis. Moreover, these cells served as an independent marker of disease‐free and overall survival of patients with CRC. Their data indicate that the number of HSP47‐positive spindle cells in the stroma of CRC may serve as a novel predictive biomarker of LN metastasis, early recurrence and poor prognosis.     

miR-103/107 promote metastasis of colorectal cancer by targeting the metastasis suppressors DAPK and KLF4

Metastasis is the major cause of poor prognosis in colorectal cancer (CRC), and increasing evidence supports the contribution of miRNAs to cancer progression. Here, we found that high expression of miR-103 and miR-107 (miR-103/107) was associated with metastasis potential of CRC cell lines and poor prognosis in patients with CRC. We showed that miR-103/107 targeted the known metastasis suppressors death-associated protein kinase (DAPK) and Krüppel-like factor 4 (KLF4) in CRC cells, resulting in increased cell motility and cell-matrix adhesion and decreased cell-cell adhesion and epithelial marker expression. miR-103/107 expression was increased in the presence of hypoxia, thereby potentiating DAPK and KLF4 downregulation and hypoxia-induced motility and invasiveness. In mouse models of CRC, miR-103/107 overexpression potentiated local invasion and liver metastasis effects, which were suppressed by reexpression of DAPK or KLF4. miR-103/107-mediated downregulation of DAPK and KLF4 also enabled the colonization of CRC cells at a metastatic site. Clinically, the signature of a miR-103/107 high, DAPK low, and KLF4 low expression profile correlated with the extent of lymph node and distant metastasis in patients with CRC and served as a prognostic marker for metastasis recurrence and poor survival. Our findings therefore indicate that miR-103/107-mediated repression of DAPK and KLF4 promotes metastasis in CRC, and this regulatory circuit may contribute in part to hypoxia-stimulated tumor metastasis. Strategies that disrupt this regulation might be developed to block CRC metastasis.     

miR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer

Colorectal cancer (CRC) is one of the most common and deadly forms of cancer. Despite improved treatment modalities, post-operative recurrence and metastasis remain the major problems for extending patient survival after surgery. This highlights the need to search for biomarkers for prognostication and treatment stratification of colorectal cancer patients. In this study, we applied the SYBR-green quantitative PCR-based array approach to screen for differentially expressed miRNAs between patients with short (<50 months, range 10-33 months) and long survival (≥ 50 months, range 50-152 months). The selected candidate prognostic miRNAs were validated in a cohort of 50 CRC patients by TaqMan quantitative PCR. We found that high expression of miR-185 and low expression of miR-133b were correlated with poor survival (p=0.001 and 0.028, respectively) and metastasis (p=0.007 and 0.036, respectively) in colorectal cancer. Our findings suggest the potential prognostic values of these miRNAs for predicting clinical outcome after surgery.     

Prognostic significance of PDCD4 expression and association with microRNA-21 in each Dukes' stage of colorectal cancer patients

Down-regulation of the novel tumor suppressor gene programmed cell death 4 (PDCD4) was demonstrated in several types of cancer and regulation by micro-RNA is gaining attention. However, the clinical significance of the PDCD4 gene in colorectal cancer (CRC) patients still remains unclear. In particular, the significance of PDCD4 mRNA expression in each tumor stage has not been reported. In this study, we evaluated the prognostic value of PDCD4 expression in each Dukes' stage of CRC patients. Furthermore, relationships between the PDCD4 mRNA and microRNA-21 (miR-21) were evaluated. Tumor tissues and normal adjacent tumor tissues from 326 patients with CRC (Dukes' stage A, 44 cases; Dukes' B, 118 cases; Dukes' C, 100 cases; Dukes' D, 64 cases) were examined. The PDCD4 mRNA was investigated by the quantitative real-time RT-PCR method and miR-21 was examined by TaqMan microRNA assays. The overall survival rates (OS) and disease-free survival rates (DFS) of low PDCD4 patients were significantly worse than those of patients with high expression. In analysis of each tumor stage, OS and DFS of patients with low PDCD4 levels were significantly worse than those with high PDCD4 levels in Dukes' stage B and C. In Dukes' stage D, patients with low PDCD4 expression showed a significant worse OS compared to those of patients with high PDCD4 expression. In contrast, no significant differences were seen between these groups in patients with Dukes' stage A. PDCD4 expression in CRC tissues was an independent prognostic factor in Dukes' stage B, C and D. Significant inverse correlations were demonstrated between PDCD4 and miR-21. The reduced PDCD4 mRNA expression is associated with poor prognosis in CRC patients with Dukes' stage B, C and D. Furthermore, PDCD4 mRNA levels were negatively regulated by miR-21in each tumor stage of CRC.     

p-mTOR蛋白在结直肠癌组织中的表达及患者预后判断中的价值

目的：检测p-mTOR（Ser2448，活化形式的mTOR）蛋白在结直肠癌中的表达变化并评价其用于判断患者预后的价值。方法：采用组织芯片-免疫组织化学染色技术，检测441例结直肠癌及其配对癌旁正常组织中p-mTOR的表达，收集患者至少5年的随访信息，并分析其表达水平与临床病理指标及患者预后的相关性。结果：免疫组织化学染色结果显示p-mTOR在癌旁正常结直肠上皮细胞中阳性表达率为4%（17/441），而在结直肠癌组织中阳性表达率为58%（254/441），两者间差异显著（P < 0.01）。统计分析结果显示，在结直肠癌组织中，p-mTOR的表达水平与肿瘤分级、淋巴结转移、远处转移及病理分期显著正相关（P均 < 0.05）。同时，p-mTOR的表达水平与结直肠癌患者的预后显著相关（P均 < 0.05），p-mTOR高表达患者的无病生存期和总生存期分别为52和60个月，明显短于p-mTOR低表达患者的71和70个月。Cox多因素分析结果显示p-mTOR表达水平为结直肠癌患者的独立预后因素。结论：p-mTOR在结直肠癌组织中表达上调，其高表达与结直肠癌患者预后不良相关，有可能作为预测结直肠癌患者术后死亡及复发转移风险的候选分子标志物。     

p-mTOR蛋白在结直肠癌组织中的表达及患者预后判断中的价值

目的:检测p-mTOR(Ser2448,活化形式的m TOR)蛋白在结直肠癌中的表达变化并评价其用于判断患者预后的价值。方法:采用组织芯片-免疫组织化学染色技术,检测441例结直肠癌及其配对癌旁正常组织中p-mTOR的表达,收集患者至少5年的随访信息,并分析其表达水平与临床病理指标及患者预后的相关性。结果:免疫组织化学染色结果显示p-mTOR在癌旁正常结直肠上皮细胞中阳性表达率为4%(17/441),而在结直肠癌组织中阳性表达率为58%(254/441),两者间差异显著(P<0.01)。统计分析结果显示,在结直肠癌组织中,p-mTOR的表达水平与肿瘤分级、淋巴结转移、远处转移及病理分期显著正相关(P均<0.05)。同时,p-mTOR的表达水平与结直肠癌患者的预后显著相关(P均<0.05),p-mTOR高表达患者的无病生存期和总生存期分别为52和60个月,明显短于p-mTOR低表达患者的71和70个月。Cox多因素分析结果显示p-mTOR表达水平为结直肠癌患者的独立预后因素。结论:p-mTOR在结直肠癌组织中表达上调,其高表达与结直肠癌患者预后不良相关,有可能作为预测结直肠癌患者术后死亡及复发转移风险的候选分子标志物。     

Depletion of tumor suppressor miRNA-148a in plasma relates to tumor progression and poor outcomes in gastric cancer

Recent studies identified that low levels of tumor suppressor microRNAs in plasma/serum relate to tumor progression and poor outcomes in cancers. This study explored decreased tumor suppressor microRNA (miRNA) plasma levels in gastric cancer (GC) patients to clarify their potential as novel biomarkers and therapeutic targets. We focused on five candidates (miR-148a, miR-101, miR-129, miR-145 and miR-206) of tumor suppressor miRNAs in GC by a systematic review of NCBI database. Of these, miR-148a levels were significantly down-regulated in plasma of GC patients compared to healthy volunteers by test- and validation-scale analyses (P<0.0001). A Low level of plasma miR-148a was significantly associated with venous invasion, lymph node metastasis, advanced stage and peritoneal recurrence, and was an independent poor prognostic factor (P=0.0296, Hazard ratio 4.2). Overexpression of miR-148a in GC cells inhibited cell proliferation, migration, invasion and epithelial-mesenchymal transition. In vivo, the restoration and maintenance of miR-148a in plasma significantly inhibited tumor growth in mice with peritoneal metastasis (P=0.0050). In conclusions, depletion of the tumor suppressor miRNA-148a in plasma relates to tumor progression and poor outcomes. The restoration of the blood miR-148a level might be a novel nucleic acid anticancer therapy for GC.     

MicroRNA-106b promotes colorectal cancer cell migration and invasion by directly targeting DLC1

Background

Growing evidence suggests that microRNAs (miRNAs) play an important role in tumor development, progression and metastasis. Aberrant miR-106b expression has been reported in several cancers. However, the role and underlying mechanism of miR-106 in colorectal cancer (CRC) have not been addressed.

Methods

Quantitative RT-PCR(qRT-PCR) was performed to evaluate miR-106b levels in CRC cell lines and patient specimens. Cell proliferation was detected using MTT assay, and cell migration and invasion ability were evaluated by wound healing assay and transwell assay. The target gene of miR-106b was determined by qRT-PCR, western blot and luciferase assays.

Results

miR-106b was significantly up-regulated in metastatic CRC tissues and cell lines, and high miR-106b expression was associated with lymph node metastasis and advanced clinical stage. In addition, miR-106b overexpression enhances, whereas miR-106b depletion reduces CRC cell migration and invasion. Moreover, we identify DLC1 as a direct target of miR-106b, reveal its expression to be inversely correlated with miR-106b in CRC samples and show that its re-introduction reverses miR-106b-induced CRC cell migration and invasion. Furthermore, survival analyses showed the patients with high mi-106b/low DLC1 had shorter overall survival (OS) and disease-free survival (DFS) rates, and confirmed miR-106b may be an independent prognostic factor for OS and DFS in CRC patients.

Conclusions

Our findings indicate that miR-106b promotes CRC cell migration and invasion by targeting DLC1. This miRNA may serve as a potential prognostic biomarker and therapeutic target for CRC.     

Clinicopathological and prognostic significance of microRNA-107 and its relationship to DICER1 mRNA expression in gastric cancer

microRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression. It is known that miRNA-107 (miR-107) promotes cancer invasion and metastasis. However, the relationship between clinicopathological factors and the prognostic significance of miR-107 for gastric cancer patients remains elusive. In this study, we evaluated the prognostic value of miR-107 using tissue samples from gastric cancer patients. Furthermore, the relationship between miR-107 and the mRNA levels of its target gene DICER1 was examined. The expression levels of miR-107 and DICER1 mRNA in tumor tissues and adjacent normal tissues of 161 gastric cancer patients were examined (TNM stage I, 29 patients; stage II, 31 patients; stage III, 51 patients and stage IV, 50 patients). miR-107 levels were measured by Taqman microRNA assays, and DICER1 mRNA levels were measured by the Taqman real-time RT-PCR method. In the analysis by real-time PCR-based miRNA arrays using pooled RNA samples from five gastric cancer patients, expression of miR-107, miR-21, miR-196a, miR-26b, miR-9, miR-142-3p, miR-30b, miR-150, miR-191 and miR-17 was found to be upregulation. The mean expression level of miR-107 was significantly higher in the tumor tissues compared to that of normal tissues. In the comparison of clinicopathological factors, miR-107 expression showed significant association with depth of tumor invasion, lymph node metastasis and stage. In Kaplan-Meier survival curve analysis, overall survival rates (OS) and disease-free survival rates (DFS) of patients with high miR-107 expression were significantly worse than those of patients with low miR-107 expression. In the Cox multivariate analysis, it was shown that miR-107 expression in gastric cancer tissues was an independent prognostic factor for OS and DFS. Significant inverse correlations were demonstrated between miR-107 and DICER1 mRNA. Our results indicate that miR-107 may be useful as an effective biomarker for prediction of a poor prognosis in gastric cancer patients.     

microRNA-320a inhibits tumor invasion by targeting neuropilin 1 and is associated with liver metastasis in colorectal cancer

MicroRNAs (miRNAs) have been implicated in regulating diverse cellular pathways. Although there is emerging evidence that various miRNAs function as oncogenes or tumor suppressors in colorectal cancer (CRC), the role of miRNAs in mediating liver metastasis remains unexplored. The expression profile of miRNAs in liver metastasis and primary CRC tissues was analyzed by miRNA microarrays and verified by real-time polymerase chain reaction (PCR). In 62 CRC patients, the expression levels of miR-320a were determined by real-time PCR, and the effects on migration and invasion of miR-320a were determined using a transwell assay. miR-320a target genes were confirmed by luciferase assay, real-time PCR and western blot analysis. A set of miRNAs was found to be dysregulated in the liver metastasis tissues compared to matched primary CRC tissues, and the expression levels of miR-320a were significantly decreased in the liver metastasis tissues examined. miR-320a was correlated with tumor progression in CRC. miR-320a was downregulated in liver metastatic colon cancer cells and inhibited liver metastatic colon cancer cell migration and invasion. miR-320a directly binds to the 3'UTR of neuropilin 1 (NRP-1), a protein that functions as a co-receptor of vascular epithelial growth factor. miR-320a downregulated the expression of NRP-1 at both the mRNA and protein levels. These data demonstrated that miR-320a may be useful for identifying CRC patients that are at an elevated risk for developing liver metastasis. Our findings suggest that miR-320a may be a novel therapeutic candidate for the treatment of colorectal cancer.     

血清中miR-29a和miR-92a在结直肠癌诊断和预后判断中的价值

目的探讨血清微小RNA（miR-29a和miR-92a）在结直肠癌（CRC）诊断和预后判断中的价值。方法选取无转移的结直肠癌患者50例和存在肝转移的患者48例,同时募集50名健康志愿者为对照组,按类似的年龄和性别相匹配的队列组合。应用实时荧光定量聚合酶链反应（PCR）法检测微小RNA（miR-29a和miR-92a）水平,判断该血清微小RNA在结直肠癌早期诊断和预后判断中的价值。结果结直肠癌患者血清中miR-29a和miR-92a水平均显著高于健康对照者（P〈0.01）;血清miR-29a和miR-92a分别进行结直肠癌诊断时的灵敏度为71.4%和75.3%,特异度为84.0%和88.3%;结直肠癌肝转移患者血清中miR-29a和miR-92a水平均显著高于未转移的CRC患者（P〈0.05）;miR-29a和miR-92a分别鉴别转移性与非转移性CRC患者的敏感性为79.4%和78.6%,特异性为85.3%和86.6%。结论 miR-29a和miR-92a可能是新的非侵入性指标用于结直肠癌患者的早期诊断,血清中miR-29a和miR-92a水平升高与结直肠癌患者预后有关,miR-29a和miR-92a有望成为结直肠癌筛查和早期诊断和预后判断的指标。     

Clinical significance of miR-22 expression in patients with colorectal cancer

MicroRNAs (miRNAs) are non-coding RNAs that have been shown to be aberrantly expressed in several tumor types. Of these miRNAs, miR-22 as tumor suppressor has been shown to play a crucial role in human carcinogenesis. However, its association with the clinicopathological features of colorectal cancer has yet to be addressed. In this study, we compared the expression of miR-22 between colorectal cancer tissues and the normal adjacent mucosa using a quantitative real-time RT-PCR. The association of miR-22 expression with clinicopathological characters was analyzed by appropriate statistical analysis. Kaplan?CMeier analysis and Cox proportional hazards regression models were used to investigate the associations of miR-22 expression with survival of patients. Results showed that the relative expression levels of miR-22 were significantly lower in colorectal cancer tissues than those in the normal adjacent mucosa, and low expression of miR-22 correlated with liver metastasis. Kaplan?CMeier analysis indicated that patients with reduced miR-22 had a poor overall survival. Moreover, the multivariate analysis showed that reduced expression of miR-22 was an independent predictor of overall survival. Our data indicate the potential of miR-22 as a novel prognostic biomarker for CRC.     

Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer

BackgroundCirculating microRNAs (miRNAs) are attracting major interest as potential non-invasive biomarkers for colorectal cancer (CRC). This study aimed to identify a novel serum miRNA biomarker for the early detection and/or evaluating prognosis of CRC patients.Patients and methodsComprehensive miRNA array analysis was carried out using serum samples from patients with colorectal neoplasia and healthy controls. Next, to verify whether the candidate miRNA possessed a secretory potential, we screened miRNA expression levels in culture medium from 2 CRC cell lines, followed by serum analysis from 12 stage IV CRC, 12 adenoma, and 12 control subjects. Thereafter, we validated expression of candidate miRNAs in 179 primary CRC tissues, as well as serum samples from an independent cohort of 211 CRCs, 56 adenomas, and 57 control subjects.ResultsThrough microarray analysis, we identified significantly higher levels of miRNA-1290 (miR-1290) in serum from patients with colorectal adenomas and cancers. We verified miR-1290 overexpression in serum of CRC patients in a training cohort. In the validation cohort, serum miR-1290 levels were significantly up-regulated in patients with colorectal adenomas (P < 0.0001) and cancers (P < 0.0001). Serum miR-1290 levels could robustly distinguish adenoma [area under the curve (AUC) = 0.718] and CRC patients (AUC = 0.830) from normal subjects. High miR-1290 expression in serum and tissue was significantly associated with tumor aggressiveness and poor prognosis. Moreover, serum miR-1290 levels were an independent prognostic factor [hazard ratio (HR) = 4.51; 95% confidence interval (CI) = 1.23–23.69; P = 0.0096] and an independent predictor for tumor recurrence (hazard ratio = 3.92; 95% confidence interval = 1.11–25.14; P = 0.032) in CRC.ConclusionsSerum miR-1290 is a novel biomarker for early detection, recurrence, and prognosis in CRC.     

Prognostic Value of microRNA-9 in Various Cancers: a Meta-analysis

Recently, there are more and more evidences from studies have revealed the association between microRNA-9 (miR-9) expression and outcome in multiple cancers, but inconsistent results have also been reported. It is necessary to rationalize a meta analysis of all available data to clarify the prognostic role of miR-9. Eligible studies were selected through multiple search strategies and the quality was assessed by MOOSE. Data was extracted from studies according to the key statistics index. All analyses were performed using STATA software. Twenty studies were selected in the meta-analysis to evaluate the prognostic role of miR-9 in multiple tumors. MiR-9 expression level was an independent prognostic biomarker for OS in tumor patients using multivariate and univariate analyses. High expression levels of miR-9 was demonstrated to associated with poor overall survival (OS) (HR?=?2.23, 95 % CI: 1.56–3.17, P?<?0.05) and recurrence free survival/progress free survival (RFS/PFS) (HR?=?2.08, 95 % CI: 1.33–3.27, P?<?0.05). Subgroup analysis showed that residence region (China and Japan), sample size, cancer type (solid or leukemia), follow-up months and analysis method (qPCR) did not alter the predictive value of miR-9 on OS in various cancers. Furthermore, no significant associations were detected for miR-9 expression and lymph node metastasis or distant metastasis. The present results suggest that promoted miR-9 expression is associated with poor OS in patients with general cancers.     

ERCC1在结直肠癌组织中的表达及预后价值

目的:探究核苷酸切除修复交叉互补基因1（excision repair cross-complementation gene 1，ERCC1）表达对结直肠癌（colorectal cancer，CRC）患者铂类辅助化疗的预后价值。方法:选取2011年01月至2013年01月安徽医科大学附属六安医院行CRC根治术后接受mFOLFOX6方案化疗的患者共84例，通过免疫组化方法评估ERCC1在CRC组织中表达情况，分析ERCC1表达与预后的关联。结果:ERCC1高表达30例（35.7%）。Kaplan-Meier曲线显示ERCC1高表达的CRC患者无病生存期（DFS）和总生存期（OS）均缩短（P均<0.001）。多因素COX分析显示ERCC1高表达（DFS HR=4.645，95%CI:2.045~10.548，P<0.001；OS HR=4.898，95%CI:1.971~12.170，P<0.001）是CRC患者预后的不良因素，分析各亚组患者中ERCC1表达与生存相关性得到相似的结果。复发患者中ERCC1高表达的肝肺转移占68.8%（11/16），低表达的腹腔转移为70.0%（7/10），ERCC1表达与首次复发模式显著相关（P=0.006）。结论:ERCC1表达可作为评价CRC患者预后的重要指标。ERCC1表达可能有助于预测CRC患者辅助化疗后首次复发模式。ERCC1表达的预后价值需进一步研究。     

Effect of exosome biomarkers for diagnosis and prognosis of breast cancer patients

Purpose

Exosomes are gradually detected as an indicator for diagnosis and prognosis of breast cancer in clinic and a systematic review was conducted.

Methods

A search for clinical studies published before July 1, 2017 was performed. Methods of exosome purification and identification from all studies were extracted. For diagnosis evaluation, the comparison of exosome biomarkers expression between breast cancer patients and healthy women was obtained; for prognosis prediction, the correlation between exosome biomarkers expression and chemotherapy resistance, overall survival (OS), disease-free survival (DFS), recurrence and metastasis of breast cancer was also extracted.

Results

A total of 11 studies with 921 breast cancer patients were included. Ultracentrifugation is the most frequent method to purify exosomes and transmission electron microscopy is commonly used to identify exosomes. Exosome biomarkers (such as HER2, CD47, Del-1, miR-1246 and miR-21) in breast cancer patients are significantly higher than those in healthy controls, exosomal GSTP1 and TRPC5 are related to chemotherapy resistance, exosome-carrying TRPC5, NANOG, NEUROD1, HTR7, KISS1R and HOXC are correlated to PFS, DFS or OS, and some exosomal proteins (HER2, KDR, CD49d, CXCR4 and CD44) as well as miRNAs (miR-340-5p, miR-17-5p, miR-130a-3p, miR-93-5p) are associated with tumor recurrence or distant organ metastasis.

Conclusions

Exosome biomarkers can be used for early diagnosis and prognosis of breast cancer patients in clinic.

     

High expression of CASK correlates with progression and poor prognosis of colorectal cancer

Calcium/calmodulin-dependent serine protein kinase (CASK), which localizes at cell–cell adhesion sites and binds to the heparan sulfate proteoglycan syndecan-2, is involved in cell proliferation, cytoskeletal remodeling, and cell migration. To demonstrate the role of CASK in colorectal cancer (CRC) carcinogenesis, we examined the expression of CASK and its binding protein syndecan-2 in human CRC tissues. The expression of CASK was measured in CRC specimens and the controls from adenomas and normal mucosae by immunohistochemical staining and Western blot analysis. Syndecan-2 protein level was tested in CRC samples and the controls by Western blot analysis. The correlations between CASK expression and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analyzed. Compared to the controls, both CASK and syndecan-2 expression were enhanced in CRC tissues. Furthermore, high expression of CASK and syndecan-2 was significantly correlated with advanced tumor stage, lymphatic invasion, lymph node metastasis, vascular invasion, liver metastasis, and unresectable metastatic CRC. Survival analysis showed that patients with low CASK staining had a significantly better survival compared to patients with high CASK staining. In multivariate analysis, CASK overexpression, advanced tumor stage, lymph node metastasis, vasvular invasion, and liver metastasis were independent prognostic factors of poor DFS and OS. Our present study indicates that CASK overexpression is associated with an unfavorable prognosis. CASK is an independent prognostic factor for CRC, which suggests that it is a novel and crucial predictor for CRC metastasis.