The putative tumor suppressor microRNA-497 modulates gastric cancer cell proliferation and invasion by repressing eIF4E

Accumulating evidence has shown that microRNAs are involved in multiple processes in gastric cancer (GC) development and progression. Aberrant expression of miR-497 has been frequently reported in cancer studies; however, the role and mechanism of its function in GC remains unknown. Here, we reported that miR-497 was frequently downregulated in GC tissues and associated with aggressive clinicopathological features of GC patients. Further in vitro observations showed that the enforced expression of miR-497 inhibited cell proliferation by blocking the G1/S transition and decreased the invasion of GC cells, implying that miR-497 functions as a tumor suppressor in the progression of GC. In vivo study indicated that restoration of miR-497 inhibited tumor growth and metastasis. Luciferase assays revealed that miR-497 inhibited eIF4E expression by targeting the binding sites in the 3′-untranslated region of eIF4E mRNA. qRT-PCR and Western blot assays verified that miR-497 reduced eIF4E expression at both the mRNA and protein levels. A reverse correlation between miR-497 and eIF4E expression was noted in GC tissues. Taken together, our results identify a crucial tumor suppressive role of miR-497 in the progression of GC and suggest that miR-497 might be an anticancer therapeutic target for GC patients.     

Protein arginine methyltransferase 5-mediated epigenetic silencing of IRX1 contributes to tumorigenicity and metastasis of gastric cancer

IRX1 is originally characterized as a tumor suppressor gene of gastric cancer (GC) by our group based on serially original studies. However, the molecular regulatory mechanisms of IRX1 are not clear yet. Here, we identified protein arginine methyltransferase 5 (PRMT5) as a major upstream regulator of IRX1 for determining GC progression. Expression of PRMT5 was significantly increased in human GC tissues (433 out of 602 cases, 71.93%) compared with normal gastric mucosa, and exhibited diagnostic and prognostic potential. Overexpression of PRMT5 promoted tumorigenicity and metastasis of GC cells, while knockdown of PRMT5 abrogated tumorigenicity and metastasis of GC cells in vitro and in vivo. By co-immunoprecipitation and chromatin immunoprecipitation assays, we proved that PRMT5 elevated methylation levels of tumor suppressor IRX1 promoter via recruiting DNMT3A at promoter region. Knockdown of PRMT5 in SGC7901 and NCI-N87 cells decreased the recruitment of DNMT3A at IRX1 promoter, and reduced the methylation level of IRX1 promoter, then re-activated IRX1 expression. Whereas, overexpression of PRMT5 could epigenetically suppress IRX1 expression. Overall, PRMT5 promoted tumorigenicity and metastasis of gastric cancer cells via epigenetic silencing of IRX1. Targeting PRMT5 in GC might inhibit the malignant characters of GC and drawing a novel therapeutic potential.     

A‐kinase‐interacting protein 1 facilitates growth and metastasis of gastric cancer cells via Slug‐induced epithelial‐mesenchymal transition

A‐kinase‐interacting protein 1 (AKIP1) has previously been reported to act as a potential oncogenic protein in various cancers. The clinical significance and biological role of AKIP1 in gastric cancer (GC) is, however, still elusive. Herein, this study aimed to investigate the functional and molecular mechanism by which AKIP1 influences GC. AKIP1 mRNA and protein expressions in GC tissues were examined by quantitative real‐time PCR (qRT‐PCR), Western blot and immunohistochemistry. Other methods including stably transfected against AKIP1 into gastric cancer cells, wound healing, transwell assays, CCK‐8, colony formation, qRT‐PCR and Western blot in vitro and tumorigenesis in vivo were also performed. The up‐regulated expression of AKIP1 in GC specimens significantly correlated with clinical metastasis and poor prognosis in patients with GC. AKIP1 knockdown markedly suppressed GC cells proliferation, invasion and metastasis both in vitro and in vivo. In contrast, AKIP1 overexpression resulted in the opposite effects. Moreover, mechanistic analyses indicated that Slug‐induced epithelial‐mesenchymal transition (EMT) might be responsible for AKIP1‐influenced GC cells behaviour. Our findings demonstrated that high AKIP1 expression significantly correlated with clinical metastasis and unfavourable prognosis in patients with GC. Additionally, AKIP1 promoted GC cells proliferation, migration and invasion by activating Slug‐induced EMT.     

Piezo type mechanosensitive ion channel component 1 facilitates gastric cancer omentum metastasis

The peritoneum, especially the omentum, is a common site for gastric cancer (GC) metastasis. Our aim was to expound the role and mechanisms of Piezo1 on GC omentum metastasis. A series of functional assays were performed to examine cell proliferation, clone formation, apoptosis, Ca²⁺ influx, mitochondrial membrane potential (MMP) and migration after overexpression or knockdown of Piezo1. A GC peritoneal implantation and metastasis model was conducted. After infection by si-Piezo1, the number and growth of tumours were observed in abdominal cavity. Fibre and angiogenesis were tested in metastatic tumour tissues. Piezo1 had higher expression in GC tissues with omentum metastasis and metastatic lymph node tissues than in GC tissues among 110 patients. High Piezo1 expression was associated with lymph metastasis, TNM and distant metastasis. Overexpressed Piezo1 facilitated cell proliferation and suppressed cell apoptosis in GC cells. Moreover, Ca²⁺ influx was elevated after up-regulation of Piezo1. Piezo1 promoted cell migration and Calpain1/2 expression via up-regulation of HIF-1α in GC cells. In vivo, Piezo1 knockdown significantly inhibited peritoneal metastasis of GC cells and blocked EMT process and angiogenesis. Our findings suggested that Piezo1 is a key component during GC omentum metastasis, which could be related to up-regulation of HIF-1α.     

Circular RNA UBE2Q2 promotes malignant progression of gastric cancer by regulating signal transducer and activator of transcription 3-mediated autophagy and glycolysis

Gastric cancer remains the third leading cause of cancer-related mortality worldwide. Emerging evidence has shown that circular RNAs (circRNAs) play a critical regulatory role in the occurrence and development of various cancers through sponging miRNAs or acting as RNA-binding protein (RBP) sponges. We found that circUBE2Q2 was significantly upregulated in GC tissues and cell lines. Knockdown of circUBE2Q2 inhibited proliferation, migration, invasion, and glycolysis, and increased autophagy in vitro. In addition, knockdown of circUBE2Q2 inhibited GC tumorigenicity and metastasis potential in vivo. A series of experiments were performed to confirm that circUBE2Q2 regulates GC progression via the circUBE2Q2-miR-370-3p-STAT3 axis and promotes tumor metastasis through exosomal communication. Further in vivo experiments confirmed that, combination treatment of circUBE2Q2 knocking down and STAT3 inhibitor has synergistic effects on the gastric cancer growth inhibition, which provides a possibility to enhance the sensitivity of targeted drugs to gastric cancer through targeting circUBE2Q2. Our findings revealed that circUBE2Q2 may serve as a new proliferation-promoting factor and prognostic marker in gastric cancer.Subject terms: Gastric cancer, Gastric cancer     

Reticulon 2 promotes gastric cancer metastasis via activating endoplasmic reticulum Ca2+ efflux-mediated ERK signalling

Gastric cancer ranks fourth for mortality globally among various malignant tumours, and invasion and metastasis are the major reason leading to its poor prognosis. Recently, accumulating studies revealed the role of reticulon proteins in cell growth and transmigration. However, the expression and biological function of reticulon proteins in human gastric cancer remain largely unclear. Herein, we explored the potential role of reticulon 2 (RTN2) in the progression of gastric cancer. Tissue microarray was used to determine the expression levels of RTN2 in 267 gastric cancer patients by immunohistochemistry. Gastric cancer cell lines were utilised to examine the influences of RTN2 on cellular migration and invasion abilities, epithelial-to-mesenchymal transition (EMT) and signalling pathway. In vivo studies were also performed to detect the effect of RTN2 on tumour metastasis. We found that RTN2 expression was notably upregulated in tumour tissues compared to pericarcinomatous tissues. High RTN2 expression was positively correlated with patients’ age, vessel invasion, tumour invasion depth, lymph node metastasis and TNM stage. Besides, high RTN2 staining intensity was associated with adverse survival which was further identified as an independent prognostic factor for gastric cancer patients by multivariate analysis. And the predictive accuracy was also improved when incorporated RTN2 into the TNM-staging system. RTN2 could promote the proliferation, migration and invasion of gastric cancer cells in vitro and lung metastasis in vivo. Mechanistically, RTN2 interacted with IP3R, and activated ERK signalling pathway via facilitating Ca²⁺ release from the endoplasmic reticulum, and subsequently drove EMT in gastric cancer cells. These results proposed RTN2 as a novel promotor and potential molecular target for gastric cancer therapies.Subject terms: Gastric cancer, Calcium signalling     

Alpha B‐crystallin promotes the invasion and metastasis of gastric cancer via NF‐κB‐induced epithelial‐mesenchymal transition

Alpha B‐crystallin (CRYAB) is overexpressed in a variety of cancers. However, little is known about its specific function and regulatory mechanism in gastric cancer. Here, we first explore the role of CRYAB in gastric cancer progression and metastasis. The expression of CRYAB was determined by western blot and immunohistochemistry in gastric cancer tissues. Besides, methods including stably transfected against CRYAB into gastric cancer cells, western blot, migration and invasion assays in vitro and metastasis assay in vivo were also conducted. The expression of CRYAB is up‐regulated in gastric cancer tissues compared with matched normal tissues. High expression level of CRYAB is closely correlated with cancer metastasis and shorter survival time in patients with gastric cancer. Additionally, CRYAB silencing significantly suppresses epithelial‐mesenchymal transition (EMT), migration and invasion of gastric cancer cells in vitro and in vivo, whereas CRYAB overexpression dramatically reverses these events. Mechanically, CRYAB facilitates gastric cancer cells invasion and metastasis via nuclear factor‐κ‐gene binding (NF‐κB)‐regulated EMT. These findings suggest that CRYAB expression predicts a poor prognosis in patients with gastric cancer. Besides, CRYAB contributes to gastric cancer cells migration and invasion via EMT, mediated by the NF‐κB signalling pathway, thus possibly providing a novel therapeutic target for gastric cancer.     

KIAA1429 regulates cell proliferation by targeting c-Jun messenger RNA directly in gastric cancer

N6-methyladenosine (m6A) modification regulatory proteins are involved in the development of many types of cancer. KIAA1429 serves as a scaffold in bridging the catalytic core components of the m6A methyltransferase complex. The role of KIAA1429 in gastric cancer and its related mechanism has not been reported upon. The expression of KIAA1429 was detected in human gastric cancer tissues and cell lines by quantitative real-time polymerase chain reaction and western blot. The effects of KIAA1429 on gastric cancer proliferation were evaluated by cell counting kit assays, colony formation assays, flow cytometry assay, and in vivo experiments with nude mice. And messenger RNA (mRNA) high-throughput sequencing, RNA immunoprecipitation assay (RIP), luciferase assay, and a rescue experiment were used to identify the relationship between KIAA1429 and its specific targeted gene, c-Jun. We found that KIAA1429 was upregulated in gastric cancer tissues, and expressed lower in adjacent tissues. The upregulated KIAA1429 promoted proliferation and downregulated KIAA1429 was proved to inhibit proliferation of gastric cancer in vitro and in vivo. Then, we identified the potential KIAA1429 regulating gene as c-Jun by mRNAs high-throughput sequencing and RIP assay. By luciferase assay, we verified that KIAA1429 regulated the expression of c-Jun in an m6A-independent manner. Finally, the overexpression of c-Jun rescued the inhibition of proliferation caused by KIAA1429 knockdown in gastric cancer cells. KIAA1429 could act as an oncogene in gastric cancer by stabilizing c-Jun mRNA in an m6A-independent manner. This highlights the functional role for KIAA1429 as a potential prognostic biomarker and therapeutic target in gastric cancer.     

Wnt7a,frequently silenced by CpG methylation,inhibits tumor growth and metastasis via suppressing epithelial-mesenchymal transition in gastric cancer

Wnt7a is a member of the Wnt family and has been reported to be involved in the carcinogenesis and progression of many types of human cancer. However, little is known about Wnt7a expression and function in gastric cancer (GC). In the present study, Wnt7a expression in GC tissues and cells was investigated, the correlation between Wnt7a expression and the prognosis was also examined. The effects of Wnt7a on proliferation, invasion, and metastasis were evaluated in vitro and in vivo. Furthermore, the expression of epithelial-mesenchymal transition (EMT) markers and hypermethylation of the Wnt7a promoter were both detected. Wnt7a was downregulated in GC and its expression was associated with poor prognosis of patients with GC. Moreover, upregulation of Wnt7a significantly suppressed the growth, invasion, and metastasis abilities of GC cells in vitro and in vivo. Mechanistically, Wnt7a was found to inhibit EMT process of GC cells. In addition, the reducing expression of Wnt7a was due to methylation of 5′-CpG island within the promoter. Furthermore, the tumor suppressor role of Wnt7a is independent of canonical Wnt/β-catenin signaling in GC cells. In conclusion, our findings demonstrated that Wnt7a could be used as a potential diagnostic marker and target for GC management.     

HOXB7在胃癌组织中的表达及其临床意义

目的:分析同源异型盒基因B7(Homeobox B7,HOXB7)在人胃癌组织中的表达情况,并探讨HOXB7的表达与胃癌患者临床病理特征和预后的关系。方法:收集行手术切除的胃癌组织及对应癌旁组织共120例,采用实时定量PCR(q RT-PCR)技术、蛋白印迹(Western blot)和免疫组化染色分别检测HOXB7m RNA水平及蛋白水平在胃癌及对应癌旁组织中的表达,通过卡方检验分析HOXB7表达水平与胃癌患者临床病理因素间的相关性,采用单因素及多因素Cox回归模型评估HOXB7在胃癌风险评估中的作用,Kaplan-Meier生存曲线分析HOXB7表达水平与胃癌患者无瘤生存期和总生存期的关系。结果:胃癌组织中HOXB7 m RNA和蛋白表达水平均显著高于对应癌旁组织(P0.05);HOXB7蛋白表达与肿瘤临床分期、浸润深度及淋巴结转移均具有显著相关性(P0.05),而与患者性别、年龄、分化程度及远处转移均无显著相关性(P0.05)。单因素和多因素Cox分析提示HOXB7可以作为评估胃癌患者预后的独立风险因素。Kaplan-Meier生存分析结果显示高表达HOXB7的胃癌患者无瘤生存时间和总生存时间均显著低于HOXB7低表达患者组(P0.01)。结论:HOXB7蛋白在胃癌组织中高表达,并与胃癌的恶性表型有关,可能参与胃癌发生及恶性进展过程,可作为判断胃癌患预后的重要参考指标。     

EZH2在胃癌组织中的表达及与Hp-L型感染关系的探讨

目的探讨EZH2在胃癌组织中表达的意义及与幽门螺杆菌L型(Helicobacter pylori-L,Hp-L)感染的关系。方法 (1)应用免疫组织化学Elivision法和革兰染色法检测80例胃癌组织及30例癌旁组织(对照组)中EZH2蛋白的表达和Hp-L型的感染情况;(2)采用逆转录多聚酶链反应(RT-PCR)技术检测30例新鲜胃癌组织及对应切缘正常胃黏膜组织(对照组)中EZH2的mRNA表达。结果胃癌组EZH2蛋白表达的阳性率高于对照组(P<0.05),且EZH2表达水平升高与肿瘤大小、浸润深度、淋巴结转移和TNM分期有关(P<0.05),与性别、年龄无关(P>0.05);RT-PCR显示,肿瘤组织、远端正常对照组织的EZH2表达量差异明显(P<0.01)。胃癌组Hp-L型检出率78.8%(63/80)与对照组23.3%(7/30)有显著性差异(P<0.05),与免疫组化Hp-L型抗原表达率73.8%(59/80)无显著性差异(P>0.05),Hp-L检出阳性率为71.3%(57/80);癌组中Hp-L型感染阳性组的EZH2表达阳性率高于Hp-L型阴性组(P<0.05),且Hp-L型阳性率和EZH2蛋白的表达呈正相关(r=0.250,P<0.05)。结论 EZH2蛋白和mRNA在胃癌中的表达增加,且与胃癌的浸润、转移相关,其机制可能与幽门螺杆菌L型(Hp-L型)感染有关。     

Downregulation of tumor suppressor QKI in gastric cancer and its implication in cancer prognosis

Gastric cancer (GC) is the fourth most common cancer and second leading cause of cancer-related death worldwide. RNA-binding protein Quaking (QKI) is a newly identified tumor suppressor in multiple cancers, while its role in GC is largely unknown. Our study here aimed to clarify the relationship between QKI expression with the clinicopathologic characteristics and the prognosis of GC. In the 222 GC patients' specimens, QKI expression was found to be significantly decreased in most of the GC tissues, which was largely due to promoter hypermethylation. QKI overexpression reduced the proliferation ability of GC cell line in vitro study. In addition, the reduced QKI expression correlated well with poor differentiation status, depth of invasion, gastric lymph node metastasis, distant metastasis, advanced TNM stage, and poor survival. Multivariate analysis showed QKI expression was an independent prognostic factor for patient survival.     

Surgical site infections following colorectal cancer surgery: a randomized prospective trial comparing common and advanced antimicrobial dressing containing ionic silver

Background

The role of annexin II in the development and progression of gastric cancer was explored.

Methods

Real-time PCR was conducted to detect annexin II and S100A6 mRNA expression. Protein expressions of annexin II and S100A6 were also examined by immunohistochemistry in 436 clinicopathologically characterized gastric cancer cases.

Results

The expression of annexin II and S100A6 mRNA differ significantly among gastric tumor tissue and matched non-cancerous gastric mucosa. Protein levels of annexin II and S100A6 were up-regulated in gastric cancer compared with adjacent non-cancerous tissues. High expression of annexin II correlated with age, location of tumor, size of tumor, differentiation, histological type, depth of invasion, vessel invasion, lymph node metastasis, distant metastasis and Tumor, Node, Metastasis (TNM) stage, and also with expression of S100A6. Further multivariate analysis suggested that expression of annexin II and S100A6 were independent prognostic indicators for gastric cancer. Cumulative five-year survival rates of patients with high expression of both annexin II and S100A6 was significantly lower than those with low expression of both.

Conclusion

Expression of annexin II in gastric cancer was significantly associated with depth of invasion, lymph node metastasis and distant metastasis, TNM stage, high S100A6 expression, and poor prognosis. Annexin II and S100A6 proteins could be useful prognostic marker to predict tumor progression and prognosis in gastric cancer.     

KDM4B promotes gastric cancer metastasis by regulating miR-125b-mediated activation of Wnt signaling

Emerging evidence has demonstrated that the aberrant expression of histone-modifying enzymes such as histone demethylases contributes to gastric carcinogenesis and progression. The role of KDM4B in cancer progression has been gradually revealed. However, the underlying mechanisms regulating gastric cancer metastasis of KDM4B remain unclear. In the present study we determined KDM4B expression in gastric cancer and its biologic function in vitro and in vivo. We found that KDM4B expression was significantly increased in most gastric cancer tissues compared with the adjacent normal tissues. Upregulated expression of KDM4B in human gastric cancer was correlated with poor prognosis. In vitro, KDM4B overexpression in AGS cells promoted cell invasion, whereas knockdown of KDM4B inhibited cell invasion. Furthermore, KDM4B overexpression also promoted tumor metastasis in vivo. Mechanistically, KDM4B upregulated miR-125b expression and activated Wnt signaling pathway. More important, miR-125b partially mediated KDM4B-induced activation of Wnt signaling. Finally, we demonstrated that KDM4B promoted gastric cancer cell invasion in vitro and cancer metastasis in vivo, at least in part, by upregulating miR-125b expression. These data provided novel insights on the role of KDM4B-driven gastric cancer metastasis and indicated that KDM4B may be served as a potential target for gastric cancer.     

METTL16 promotes cell proliferation by up-regulating cyclin D1 expression in gastric cancer

N6-methyladenosine (m6A) is a well-known modification of RNA. However, as a key m6A methyltransferase, METTL16 has not been thoroughly studied in gastric cancer (GC). Here, the biological role of METTL16 in GC and its underlying mechanism was studied. Immunohistochemistry was used to detect the expression of METTL16 and relationship between METTL16 level and prognosis of GC was analysed. CCK8, colony formation assay, EdU assay and xenograft mouse model were used to study the effect of METTL16. Regulatory mechanism of METTL16 in the progression of GC was studied through flow cytometry analysis, RNA degradation assay, methyltransferase inhibition assay, RT-qPCR and Western blotting. METTL16 was highly expressed in GC cells and tissues and was associated with prognosis. In vitro and in vivo experiments confirmed that METTL16 promoted proliferation of GC cells and tumour growth. Furthermore, down-regulation of METTL16 inhibited proliferation by G1/S blocking. Significantly, we identified cyclin D1 as a downstream effector of METTL16. Knock-down METTL16 decreased the overall level of m6A and the stability of cyclin D1 mRNA in GC cells. Meanwhile, inhibition of methyltransferase activity reduced the level of cyclin D1. METTL16-mediated m6A methylation promotes proliferation of GC cells through enhancing cyclin D1 expression.     

Aldolase A as a prognostic factor and mediator of progression via inducing epithelial–mesenchymal transition in gastric cancer

Glycolysis is regarded as the hallmark of cancer development and progression, which involves a multistep enzymatic reaction. This study aimed to explore the clinicopathological significance and potential role of glycolytic enzyme aldolase A (ALDOA) in the carcinogenesis and progression of gastric cancer (GC). ALDOA was screened from three paired liver metastasis tissues and primary GC tissues and further explored with clinical samples and in vitro studies. The ALDOA protein level significantly correlated with a larger tumor diameter (P = .004), advanced T stage (P < .001), N stage (P < .001) and lymphovascular invasion (P = .001). Moreover, the expression of ALDOA was an independent prognostic factor for the 5‐year overall survival and disease‐free survival of patients with GC in both univariate and multivariate survival analyses (P < .05). Silencing the expression of ALDOA in GC cell lines significantly impaired cell growth, proliferation and invasion ability (P < .05). Knockdown of the expression of ALDOA reversed the epithelial–mesenchymal transition process. Mechanically, ALDOA could affect the hypoxia‐inducible factor (HIF)‐1α activity as demonstrated by the HIF‐1α response element–luciferase activity in GC cells. Collectively, this study revealed that ALDOA was a potential biomarker of GC prognosis and was important in the carcinogenesis and progression of human GC.     

RPS15A promotes gastric cancer progression via activation of the Akt/IKK‐β/NF‐κB signalling pathway

This study aimed to investigate the clinical significance, potential biological function and underlying mechanism of RPS15A in gastric cancer (GC) progression. RPS15A expression was detected in 40 pairs of GC tissues and matched normal gastric mucosae (MNGM) using qRT‐PCR analysis. Immunohistochemistry assay was conducted using a tissue microarray including 186 primary GC samples to characterize the clinical significance of RPS15A. A series of in vitro and in vivo assays were performed to elucidate the biological function of RPS15A in GC development and underlying molecular mechanisms. The expression of RPS15A was significantly up‐regulated in GC samples compared to MNGM, and its expression was closely related to TNM stage, tumour size, differentiation, lymph node metastasis and poor patient survival. Ectopic expression of RPS15A markedly enhanced the proliferation and metastasis of GC cells both in vitro and in vivo. RPS15A overexpression also promoted the epithelial‐mesenchymal transition (EMT) phenotype formation of GC cells. Investigations of underlying mechanisms found that RPS15A activated the NF‐κB signalling pathway by inducing the nuclear translocation and phosphorylation of the p65 NF‐κB subunit, transactivation of NF‐κB reporter and up‐regulating target genes of this pathway. In addition, RPS15A overexpression activated, while RPS15A knockdown inhibited the Akt/IKK‐β signalling axis in GC cells. And both Akt inhibitor LY294002 and IKK inhibitor Bay117082 neutralized the p65 and p‐p65 nuclear translocation induced by RPS15A overexpression. Collectively, our findings suggest that RPS15A activates the NF‐κB pathway through Akt/IKK‐β signalling axis, and consequently promotes EMT and GC metastasis. This newly identified RPS15A/Akt/IKK‐β/NF‐κB signalling pathway may be a potential therapeutic target to prevent GC progression.     

乳腺癌中丝／苏氨酸蛋白激酶Plk1mRNA的表达及其预后价值

目的：检测乳腺癌细胞和组织中丝／苏氨酸蛋白激酶Plk1基因mRNA的表达情况并分析其预后价值。方法：应用半定量RT-PCR方法分析3株人乳腺癌细胞和1株正常乳腺上皮细胞中Plk1基因mRNA的表达水平。同时分析84例乳腺癌及对应的癌旁正常乳腺上皮组织中Plk1mRNA的表达水平。统计学分析Plk1mRNA表达水平与乳腺癌患者年龄、肿瘤大小、组织分化程度、淋巴结转移状况、TNM分期和雌激素受体（ER）等临床病理参数之间的关系,以及与预后之间的关系。结果：Plk1基因mRNA在乳腺癌细胞中的相对表达水平显著高于其在正常乳腺上皮细胞中的相对表达水平（P值均小于〈0．05）。另外,Plk1mRNA在乳腺癌组织中平均表达水平（0．88±0．18）显著高于其在癌旁正常乳腺上皮组织中平均表达水平（0．22±0．10;P〈0．01）。统计学分析结果袁明：Plk1mRNA表达水平和乳腺癌患者的淋巴结转移状况及TNM分期密切相关（P=0．009或0．007）。Kaplan—Meier生存曲线分析结果表明：高Plk1mRNA表达水平的乳腺癌患者的5年无疾病进展率及总体生存率均显著低于低Plk1mRNA表达水平的乳腺癌患者（P=0．0026及0．0136）。COX模型的多因素预后分析结果表明：Plk1基因mRNA表达水平是乳腺癌患者的一个独立的预后因素（HR=4．764,95％CI：1．341-6．123,P=0．0025）。结论：Plk1在乳腺癌组织呈现高表达水平,其mRNA表达水平有望成为临床乳腺癌患者一个重要的预后判断分子指标。     

KIF14 promotes tumor progression and metastasis and is an independent predictor of poor prognosis in human gastric cancer

The kinesin family member 14 (KIF14) is a potential oncogene and is involved in the metastasis of various cancers. Nevertheless, its function in gastric cancer (GC) remains poorly defined. The expression of KIF14 was examined in GC cell lines and a clinical cohort of GC specimens by qPCR, western blotting and immunohistochemistry (IHC) staining. The relationship between KIF14 expression and the clinicopathological features was analyzed. The effect of KIF14 on cell proliferation, colony formation, invasion and migration were investigated in vitro and in vivo. The expression of KIF14 was significantly increased in the GC tissues and cell lines. High KIF14 expression was associated with tumor stage, tumor-node-metastasis (TNM) stage and metastasis. KIF14 was an independent prognostic factor for the overall survival of GC, and a higher expression of KIF14 predicted a poorer survival. KIF14 silencing resulted in attenuated proliferation, invasion and migration in human gastric cancer cells, whereas KIF14 ectopic expression facilitated these biological abilities. Notably, the depressed expression of KIF14 inhibited Akt phosphorylation, while overexpressed KIF14 augmented Akt phosphorylation. Additionally, there was a significant correlation between the expression of KIF14 and p?Akt in GC tissues. Importantly, the proliferation, invasion and migration of the GC cells, which was promoted by KIF14 overexpression, was abolished by the Akt inhibitor MK-2206, while Akt overexpression greatly rescued the effects induced by KIF14 knockdown. Our findings are the first to demonstrate that KIF14 is overexpressed in GC, is correlated with poor prognosis and plays a crucial role in the progression and metastasis of GC.