Advanced Tumor Size Research Articles

LINC00657 promotes the development of colon cancer by activating PI3K/AKT pathway.

The aim of this study was to explore whether LINC00657 can regulate cell proliferation and invasion by regulating the PI3K/AKT pathway and thus participate in the occurrence of colon cancer. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was applied to detect the expression levels of LINC00657 and E-cad in colon cancer tissues and corresponding adjacent tissues obtained from 80 patients, and the correlation was analyzed between LINC00657 expression and clinical information of patients such as prognosis, tumor size, tumor stage, and distant metastasis. The expression of LINC00657 and E-cad in colon cancer cell lines was also examined, and the effect of LINC00657 on tumor cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay and colony formation experiments. Meanwhile, transwell assay was performed to evaluate the influence of LINC00657 and CAPN7 on cell invasive ability. In addition, the effect of LINC00657 on CAPN7 and PI3K/AKT pathway was detected by Western blot assay. The expression levels of LINC00657 and E-cad in tumor tissues decreased remarkably, especially in patients who occurred distant metastasis. Compared with patients with highly-expressed LINC00657, the patients with lower level of LINC00657 had a worse prognosis and an advanced tumor size and TNM stage. Similarly, LINC00657 and E-cad also showed a decrease in colon cancer cell lines. After overexpression of LINC00657, cell viability and invasive ability decreased remarkably while cell apoptosis rate increased significantly. In addition, high expression of LINC00657 in an in vitro model significantly promoted CAPN7 expression and inhibited activation of PI3K/AKT pathway. LINC00657 had a low expression in colon cancer tissues, which could accelerate cell proliferation and invasion by activating PI3K/AKT pathway and inhibiting CAPN7 expression.

Survival in Differentiated Thyroid Cancer: Comparing the AJCC Cancer Staging Seventh and Eighth Editions.

The American Joint Committee on Cancer Cancer Staging System for differentiated thyroid cancer has been recently revised. The purpose of this study was to compare survival prognostication between the seventh and eighth editions. We retrospectively reviewed 2579 differentiated thyroid cancer patients who underwent surgery at MD Anderson Cancer Center between 2000 and 2015. Disease-specific survival (DSS) and overall survival were estimated using the Kaplan-Meier method and compared using log rank test. The effect of potential predictor was estimated using Cox proportional hazards model. Power of survival prediction was estimated using Harrell's C concordance index (C-index), and predictive capacities for DSS were estimated using proportion of variance explained (PVE). Revision of tumor-node-metastasis (TNM) categories, age cutoff, and stage reassignment in the 8th edition caused reclassification of overall stage compared with the seventh edition. The proportion of patients in stage I and II increased from 62% to 83% and 5% to 12%, respectively, while the proportion of patients in stage III and IV decreased from 20% to 2% and 14% to 3%, respectively. Ten-year DSS for stages I-IV based on the seventh edition were 100%, 97.5%, 98.3%, and 82.6%, respectively, while 10-year DSS for the corresponding stage in the eighth edition were 99.8%, 88.3%, 72.4%, and 71.9%, respectively. In multivariate analysis for both seventh edition (C-index 0.94, PVE 4.6%) and eighth edition (C-index 0.94, PVE 4.8%), the factors predictive of worse outcome for DSS were older age, advanced tumor size category, and distant metastasis while cervical lymph node metastases did not predict worse survival. For the eighth edition, patients <55 years of age with stage II disease had significantly worse DSS (p < 0.001) than patients ≥55 years with stage II disease but appeared to be similar to patients ≥55 years with stage III (p = 0.742) and IV disease (p = 0.566). Patients ≥55 years old with T3a and T3b disease had 10-year DSS of 67% and 92%, respectively (p = 0.390). The AJCC eighth edition is similar to the seventh edition in disease-specific survival prediction. Potential modifications that may improve disease-specific survival prediction in future renditions include reconsideration of T3b tumor category and upstaging classification of patients <55 years of age with distant metastases.

The long coding RNA AFAP1-AS1 promotes tumor cell growth and invasion in pancreatic cancer through upregulating the IGF1R oncogene via sequestration of miR-133a

ABSTRACTLong non-coding RNAs (lncRNAs) have been shown to play a significant role in the progression of many cancers, including pancreatic cancer (PC). However, the biological function and regulatory mechanisms of lncRNAs in PC remains largely unclear. The aim of this study was to identify and evaluate the potential functions of lncRNAs in PC and reveal the underlying mechanisms of their effects. Screening of published microarray data (GEO accession Nos. GSE16515 and GSE32688), revealed lncRNA AFAP1-AS1 to be one of the most upregulated lncRNAs in PC tissues. High expression of AFAP1-AS1 was correlated with advanced stages, tumor size and lymph node metastasis, as well as with poorer overall survival in patients with PC. Functionally, knockdown of AFAP1-AS1 by transfection with siRNA inhibited the proliferative and invasive capacities of PaCa-2 and SW1990 PC cells, promoted apoptosis of PC cells in vitro, and impaired in-vivo tumorigenicity. In particular, it was hypothesized that AFAP1-AS1 may act as a competitive endogenous RNA (ceRNA), effectively becoming a sink for miR-133a whose expression was found to be downregulated in PC tissues and cell lines, and which was negatively correlated with the expression of AFAP1-AS1. We also found that the IGF1R oncogene which is an important regulator of MEK/ERK signaling pathway, was positively regulated by AFAP1-AS1 through ameliorating miR-133a-mediated IGF1R repression in PC tissues. Moreover, we demonstrated that knockdown of IGF1R by transfection with si-IGF1R suppressed cell proliferation, invasion and migration of PaCa-2 and SW1990 PC cells, suggesting that IGF1R may function as an oncogene in PC cells. Further investigations revealed that miR-133a reversed the biological effects of AFAP1-AS1 on PC cells. Collectively, the findings provide new evidence that AFAP1-AS1 could regulate the progression of pancreatic cancer by acting as a ceRNA, and suggest it has potential for use as both a biomarker for the early detection PC and for the development of individualized therapies for PC.

MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): study protocol of a multicenter randomised controlled trial

BackgroundIn case of suspicious lymph nodes on computed tomography (CT) or fluorodeoxyglucose positron emission tomography (FDG-PET), advanced tumour size or central tumour location in patients with suspected non-small cell lung cancer (NSCLC), Dutch and European guidelines recommend mediastinal staging by endosonography (endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS)) with sampling of mediastinal lymph nodes. If biopsy results from endosonography turn out negative, additional surgical staging of the mediastinum by mediastinoscopy is advised to prevent unnecessary lung resection due to false negative endosonography findings. We hypothesize that omitting mediastinoscopy after negative endosonography in mediastinal staging of NSCLC does not result in an unacceptable percentage of unforeseen N2 disease at surgical resection. In addition, omitting mediastinoscopy comprises no extra waiting time until definite surgery, omits one extra general anaesthesia and hospital admission, and may be associated with lower morbidity and comparable survival. Therefore, this strategy may reduce health care costs and increase quality of life. The aim of this study is to compare the cost-effectiveness and cost-utility of mediastinal staging strategies including and excluding mediastinoscopy.Methods/designThis study is a multicenter parallel randomized non-inferiority trial comparing two diagnostic strategies (with or without mediastinoscopy) for mediastinal staging in 360 patients with suspected resectable NSCLC. Patients are eligible for inclusion when they underwent systematic endosonography to evaluate mediastinal lymph nodes including tissue sampling with negative endosonography results. Patients will not be eligible for inclusion when PET/CT demonstrates ‘bulky N2-N3’ disease or the combination of a highly suspicious as well as irresectable mediastinal lymph node. Primary outcome measure for non-inferiority is the proportion of patients with unforeseen N2 disease at surgery. Secondary outcome measures are hospitalization, morbidity, overall 2-year survival, quality of life, cost-effectiveness and cost-utility. Patients will be followed up 2 years after start of treatment.DiscussionResults of the MEDIASTrial will have immediate impact on national and international guidelines, which are accessible to public, possibly reducing mediastinoscopy as a commonly performed invasive procedure for NSCLC staging and diminishing variation in clinical practice.Trial registrationThe trial is registered at the Netherlands Trial Register on July 6th, 2017 (NTR 6528).

Involvement of hedgehog pathway in early onset, aggressive molecular subtypes and metastatic potential of breast cancer

BackgroundDysregulation of hedgehog pathway is observed in numerous cancers. Relevance of hedgehog pathway genes in cancer cohort and inhibition of its downstream effector (GLI1) towards metastasis in cell lines are explored in the study.MethodOne hundred fifty fresh tumours of breast cancer patients were collected for the study. Based on differential expression, panel of 6 key regulators of the pathway (SHH, DHH, IHH, PTCH1, SMO and GLI1) in microarray datasets were identified. Expressional profiles of aforementioned genes were later correlated with clinico-pathological parameters in Pakistani breast cancer cohort at transcript and protein levels. In addition, GLI1 over expressing breast cancer cell lines (MDA-MB-231 and MCF-7) were treated with GANT61 to explore its probable effects on metastasis.ResultSHH, DHH, PTCH1 and GLI1 were significantly over-expressed in tumours as compared with respective normal mammary tissues. A significant correlation of SHH, DHH and GLI1 expression with advanced tumour size, stages, grades, nodal involvement and distant metastasis was observed (p < 0.05). Over-expression of SHH, DHH and GLI1 was significantly related with patients having early onset and pre-menopausal status. Of note, hedgehog pathway was frequently up regulated in luminal B and triple negative breast cancer affected women. In addition, positive correlations were observed among aforementioned members of pathway and Ki67 (r-value: 0.63–0.78) emphasizing their role towards disease progression. Exposure of GANT61 (inhibitor for GLI1) significantly restricted cell proliferation, reduced cell motility and invasion.ConclusionRole of activated hedgehog pathway in breast cancer metastasis provides a novel target for cancer therapy against aggressive cancer subtypes.

Carcinoembryonic antigen levels correlated with advanced disease in medullary thyroid cancer

BackgroundMedullary thyroid cancer (MTC) cells are capable of secreting various tumor markers including calcitonin and carcinoembyronic antigen (CEA). The purpose of this study is to determine whether abnormal CEA levels may be used as a tumor marker to predict the severity of disease in MTC.MethodsA retrospective analysis was completed for 33 patients with MTC who had preoperative serum CEA levels. Univariate and multivariate analyses were used to quantify the relationship between serum CEA levels and tumor stage and prognosis.ResultsOn multivariate analysis, elevated preoperative CEA levels were significantly associated with the size and stage of tumor, distant metastasis, decreased biochemical cure, and mortality. There was a significant association between tumor size greater than 37 mm and elevated CEA levels (> 271 ng/ml). There was also a positive correlation with increased cancer stage (> 377 ng/ml), distant metastasis (> 405 ng/ml), and contralateral compartment location of lymph node metastasis (> 162 ng/ml). When pre-operative CEA levels are > 500 ng/ml, patient mortality was 67%.ConclusionIn this study, both pre-operative calcitonin and CEA levels were significantly correlated with the extent of disease in MTC. While calcitonin has a linear relationship with disease progression, abnormal CEA levels were a better indicator of advanced disease. CEA levels > 271 ng/ml are significant for advanced tumor size and staging, metastasis to the central compartment, and decreased chance of biochemical cure. CEA levels greater than 500 ng/ml are associated with significant patient mortality.

Survival analysis of 269 patients with adenocarcinoma of gastroesophageal junction after radical resection

Objective To analyze the prognostic factors of patients with adenocarcinoma of gastroesophageal junction (AGEJ) after radical resection. Methods In this retrospective study, 269 patients with AGEJ who underwent curative resection from March 2004 to June 2007 were enrolled. The survival curve was drawn by Kaplan-Meier method and the survival analysis was done by Log-rank test. Univariate and multivariate analyses of the prognostic factors of AGEJ were made by Cox model. Results The overall 5-year survival rate of 269 patients was 25.0% with the median survival time of 22 months. The Siewert type and the number of positive lymph nodes could influence the survival rate (both P < 0.05). Among the 269 patients, 216 (80.3%) were SiewertⅡ type, their median survival time was 30 and 12 months in the thoracic surgery group and the laparotomy group when the tumor diameter was 3-7 cm, the difference was statistically significant (χ2 = 5.036, P = 0.025). Univariate analysis showed that tumor diameter, pT, pN, operation time, age and sex were significantly associated with survival rate (all P < 0.05). Cox multivariate analysis showed that patients with a more advanced tumor size suffered from a poorer prognosis (P < 0.05). The risk of postoperative death in patients with lymph node metastasis was 1.854 times that of patients without lymph node metastasis. Conclusions Patients with AGEJ are predominantly SiewertⅡ type, the transthoracic approach or thoracoabdominal approach are reasonable selections for these patients. Tumor diameter and pN are independent prognostic factors of AGEJ patients. Key words: Adenocarcinoma; Esophagogastric junction; Cardia neoplasms; Prognosis

Wild type Kirsten rat sarcoma is a novel microRNA-622-regulated therapeutic target for hepatocellular carcinoma and contributes to sorafenib resistance

ObjectiveSorafenib is the only effective therapy for advanced hepatocellular carcinoma (HCC). Combinatory approaches targeting mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK)- and phosphatidylinositol-4,5-bisphosphate-3-kinase (PI3K)/protein-kinase B(AKT) signalling yield major therapeutic improvements....

Upregulation of LncRNA BCYRN1 promotes tumor progression and enhances EpCAM expression in gastric carcinoma.

Brain cytoplasmic RNA 1 (BCYRN1), along non-coding RNA, plays a critical role in various diseases, including some cancers. However, the expression of BCYRN1 and its roles in gastric carcinoma (GC) still remain unidentified. Thus, this study employed RT-qPCR to detect expression of BCYRN1 in 85 paired GC samples and adjacent normal tissues, and performed in vitro studies to explore effects of BCYRN1 in GC cells on cell proliferation, apoptosis and migration. We found BCYRN1 was significantly upregulated in GC samples, and its expression was positively correlated with advanced TNM stage (p = 0.0012) and tumor size (p = 0.027). Functionally, BCYRN1 knockdown by siRNA could inhibit cell proliferation, induce G1/G0 cell cycle arrest, increase apoptosis and impair migratory ability of AGS cells. Moreover, the results of RT-qPCR and western blotting indicated that knockdown of BCYRN1 notably decreased the expression of epithelial cell adhesion molecules (EpCAM). Otherwise, overexpression of BCYRN1 in GC cells (BGC-823 and SGC-7901) could reverse the effects of BCYRN1 knockdown. Taken together, our data indicate for the first time that BCYRN1 acts as an oncogenic lncRNA in GC progression and may be a potential therapeutic target in GC.

Cancer-Specific Survival Stratification Derived from Tumor Expression of Tissue Inhibitor of Metalloproteinase-2 in Non-Metastatic Renal Cell Carcinoma.

Degradation of the extracellular matrix is a prerequisite for the processes of cancer cell invasion and metastasis. The purpose of our study was to assess the association of matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-9) and their inhibitors (TIMP-1 and TIMP-2) with renal cell carcinoma (RCC) progression and cancer-specific survival (CSS), using immunohistochemical analysis of 60 formalin-fixed, paraffin-embedded sections of tumor tissue and normal tissue near the tumor from surgical T1-3bN0M0 RCC specimens. Significant overexpression of MMP-2 in tumor and normal tissue was correlated with advanced stages, tumor size, sarcomatous differentiation and clinical symptoms. Overall survival was 31.7% (55.2% M0, 9.7% M1) and CSS 56.7% (100% M0, 16.1% M1) with a follow-up of 76 (5-230) months. Fuhrman grade [HR 2.87 (95% CI: 1.28-6.45); p=0.01], tumor size [HR 1.13 (95% CI: 1.03-1.26); p=0.009] and low TIMP-2 expression [HR 0.35 (95% CI: 0.16-0.78); p=0.01] were independent predictive factors of CSS and stratified the patients into three groups with different rates of 10-year CSS; [100%, 73.9% and 20.5% for the good, intermediate and poor prognosis group respectively (p=0.000006)] . This study offers strong evidence that TIMP-2 expression in tumor tissue may play a crucial role in progression and poor prognosis in human localized and locally advanced RCC.

Positive surgical margin following radical nephrectomy is an independent predictor of local recurrence and disease-specific survival

BackgroundPositive surgical margins (PSM) are recognized as an adverse prognostic sign and are often associated with higher rates of local and systemic disease recurrence. The data regarding the oncological outcome for PSM following radical nephrectomy (RN) is limited. We examined the predictive factors for PSM and its influence on survival and site of recurrence in patients treated with RN for renal cell carcinoma (RCC).MethodsClinical, pathologic and follow-up data on 714 patients undergoing RN for kidney cancer were analyzed. Secondary analysis included 44 patients with metastatic RCC upon diagnosis who underwent cytoreductive nephrectomy (CRN). Univariate and multivariable logistic regression models were fit to determine clinicopathologic features associated with PSM. A Cox proportional-hazards regression model was used to test the independent effects of clinical and pathologic variables on survival.ResultsPSM was documented in 17 cases (2.4%). PSM were associated with tumour size, advanced pathologic stage (pT3 vs. ≤ pT2) and presence of necrosis. On multivariate analysis, cancer-specific survival (CSS) was associated with tumour stage, size, presence of necrosis and PSM. PSM was also associated with local recurrence but not distant metastasis or overall survival (OS). CSS and OS were comparable between the PSM and metastatic RCC groups, but significantly lower than the negative margin group.ConclusionsThe prevalence of PSM following RN is rare. Pathological data, including advanced stage (> pT2), tumour necrosis and tumour size, are associated with the presence of PSM. PSM is associated with tumour recurrence and CSS. Patients with PSM are a potential group for adjuvant therapy or for more careful and thorough follow-up following surgery.

Outcome and cervical metastatic spread of squamous cell cancer of the buccal mucosa, a retrospective analysis of the past 25 years.

Because of the low proportion of squamous cell carcinomas (SCCs) of the buccal mucosa within the carcinomas of the oral cavity in the Western population, data concerning metastatic pattern are sparse. Therefore, this retrospective study is focusing on the occurrence of cervical metastases (CM) and the overall outcome of this tumor entity. From January 1988 to October 2013, 113 patients were treated in the Department of Oral and Maxillofacial Surgery, Mainz, for an oral SCC of the cheek. Metastatic pattern and clinical parameters that are possibly associated with an increased risk for CM as well as overall outcome were analyzed. The average follow-up was 48 months (range: 1-248 months). A total of 55 (49%) patients were female and 58 (51%) male, with an average age of 65 ± 13 years (♀68 ± 14 years; ♂63 ± 11 years). In total, 55% of the patients either smoked and/or consumed alcohol. In total, 34% of the patients had a stage III or IV tumor, with overall 23% having CM at the time of diagnosis. During the follow-up, 50% (n = 56) of the patients developed a relapse after 12 months (median). Tumor size (P = 0.002*) and grading (P < 0.001*) are significantly associated with the occurrence of CM. Metastases (P = 0.008*) and advanced tumor size (P = 0.018) had an influence on the survival, whereas the relapse had no significant influence (P = 0.928). Five-year survival rate was 80%. SCC of the buccal mucosa shows aggressive behavior with a considerably high proportion of relapse. Since overall outcome is significantly decreased by the cervical metastatic pattern, a selective, ipsilateral neck dissection for this patient group is recommended as the primary management.

Long non-coding RNA CTA sensitizes osteosarcoma cells to doxorubicin through inhibition of autophagy.

Recently, several long non-coding RNAs (lncRNAs) have been implicated in osteosarcoma (OS). However, the regulatory roles of lncRNAs in chemotherapy resistance of OS still remain unclear. This study aimed to screen a novel lncRNA that contributes to chemotherapeutic resistance of OS, and to explore the underlying mechanisms. Our data showed that lncRNA CTA was markedly downregulated in OS tissues compared to their matched non-tumor tissues, and low expression of lncRNA CTA was significantly associated with the advanced clinical stage and tumor size. In addition, OS patients with low lncRNA CTA levels showed a worse prognosis when compared with those with high expression of lncRNA CTA. Furthermore, we report that lncRNA CTA has an inverse relationship with miR-210 expression in OS tissues. LncRNA CTA could be activated by doxorubicin (DOX), and could promote OS cell apoptosis by competitively binding miR-210, while inhibit cell autophagy. On the other hand, lncRNA CTA was downregulated in DOX-resistant OS cells. Overexpression of lncRNA CTA reduced autophagy and subsequently overcame DOX resistance of OS in vitro and in vivo. Therefore, we demonstrate that lncRNA CTA is an essential regulator in DOX-induced OS cell apoptosis, and the lncRNA CTA-miR-210 axis plays an important role in reducing OS chemoresistance.

Impact of CCL4 gene polymorphisms and environmental factors on oral cancer development and clinical characteristics.

In Taiwan, oral cancer has causally been associated with environmental carcinogens. CCL4 (C-C chemokine ligand 4), a macrophage inflammatory protein with a key role in inflammation and immune-regulation, was implicated in carcinogenesis by facilitating instability in the tumor environment. The purpose of this study was to identify gene polymorphisms of CCL4 specific to patients with oral squamous cell carcinoma (OSCC) susceptibility and clinicopathological characteristics. A total of 2,053 participants, including 1192 healthy people and 861 patients with oral cancer, were recruited for this study. Three single-nucleotide polymorphisms (SNPs) of the CCL4 gene were analyzed by a real-time PCR. We found that the T/T homozygotes of CCL4 rs1634507 G/T polymorphism and the GG haplotype of 2 CCL4 SNPs (rs1634507 and rs10491121) combined were associated with oral-cancer susceptibility. In addition, TA haplotype significantly decreased the risks for oral cancer by 0.118 fold. Among 1420 smokers, CCL4 polymorphisms carriers with the betel-nut chewing habit had a 15.476–20.247-fold greater risk of having oral cancer compared to CCL4 wild-type (WT) carriers without the betel-nut chewing habit. Finally, patients with oral cancer who had A/G heterozygotes of CCL4 rs10491121 A/G polymorphism showed a lower risk for an advanced tumor size (> T2) (p=0.046), compared to those patients with AA homozygotes. Our results suggest that the CCL4 rs1634507 SNP have potential predictive significance in oral carcinogenesis. Gene-environment interactions of CCL4 polymorphisms might influence oral-cancer susceptibility. CCL4 rs10491121 may be a factor to predict the tumor size in OSCC patients.

Perioperative blood transfusion is associated with poorer survival in patients with gastric cancer

The putative prognostic significance of perioperative blood transfusions on gastric cancers is controversial and the published results are contradictory. The aim of this study was to evaluate the prognostic influence of transfusion on Chinese gastric cancer surgery. Six hundreds and seventy-six patients who underwent curative gastrectomy for gastric cancer from 2000 to 2004 were retrospectively reviewed. Uni- and multivariate analyses of the incidence and amount of transfusion, and a comparison of the clinicopathological features were performed. Subgroup analyses of prognosis according to stage, tumor size, and pretreatment anemia were carried out. Blood transfusion was significantly associated with older age (>60 year), larger tumor (>6 cm), upper and middle location, surgical margin status, and pretreatment anemia. In addition, tumors in the transfused group were more advanced in depth of invasion, nodal stage, and TNM stage. No significant relationship was found between the amount of transfused blood and prognosis. Subgroup analyses of prognosis according to stage showed significant differences in stages II and III, between the transfused and nontransfused groups. Significant difference between the transfused and nontransfused groups could be observed in two subgroups of tumor size. Patients with or without anemia in the nontransfused group both had a longer survival time than those in the transfused group. On multivariate analysis, transfusion was shown to be an independent risk factor for poor prognosis. This study suggests that perioperative blood transfusion is associated with a significantly worse prognosis following gastric cancer surgery. The parameters such as advanced stage, tumor size, and anemia do not affect its prognostic value.

Human Epididymis Protein-4 Gene Expression as a Biomarker in Patients with Ovarian Cancer in Iran

Introduction: Ovarian cancer is one of the most common malignancies in women and the fifth cause of cancer-related deaths in women worldwide. Contrary to the challenges in developing new clinical markers using the conventional methods, recent advances in genomics and proteomics have led to identification of candidate and promising biomarkers for the diagnosis of ovarian cancer. Human epididymis protein 4 (HE4) is such a marker that has recently been reported to correlate with recurrence or progression of epithelial ovarian cancer. The purpose of this study was to measure the expression level of HE4 gene in women with ovarian cancer. Methodology: We evaluated and compared paraffin-embedded tissue samples of 20 ovarian cancer patients with 10 samples from healthy individuals. RNA was initially extracted from the samples and cDNA was synthetized. Gene expression level was then measured using real-time polymerase chain reaction (PCR). Results: Our results demonstrated that HE4 gene expression level was significantly higher in samples of patients with ovarian cancer compared with samples from healthy individuals. Moreover, higher levels of HE4 gene expression were associated with more advanced disease and larger tumor size. Conclusion: HE4 gene over-expression has the potential to be used as a biomarker for detecting early-stage ovarian cancer in women. Future more comprehensive studies are needed to confirm our findings.

Gene polymorphism of matrix metalloproteinases 3 and 9 in breast cancer

BackgroundGenetic factors have a considerable influence on the development and progress of malignancy. Matrix metallo-proteinases (MMPs) are a group of proteolytic enzymes which are proved to be involved in pathogenesis of breast cancer. Some functional single nucleotide polymorphisms (SNPs) affect the transcriptional activity of genes of MMPs. We aimed to investigate the possible association of 2 SNPs, C/T polymorphism of MMP9 gene, and 5A/6A polymorphism of MMP3 gene, with the occurrence and pathological criteria of breast cancer. Subjects and methodsThe present case control study included 59 breast cancer female patients, and 77 tumor free age matched control females. The SNPs were genotyped using polymerase chain reaction - restriction fragment length polymorphism assay. ResultsThe results have shown higher frequency of T allele of C/T MMP9 and 5A of A5/A6 MMP3 in breast cancer patients as compared to control subjects with odd ratio (OR) of 1.8 (95% CI1.02–3.26) and 1.2 (0.71–1.89), respectively. Moreover, combined 5A and T alleles had a higher risk with OR of 2.3 (1.17–4.57). When the frequency of both alleles was analyzed in comparison to prognostic pathological parameters of the disease, there was a significant association of T allele of C/T MMP9 with advanced tumor size and histological grade with OR (95%CI) 2.5 (1.12–5.64) and 1.8 (0.78–4.17) respectively. ConclusionThe results suggested that T allele of C/T MMP9 gene polymorphism is strongly linked to the incidence, growth and differentiation of breast cancer.

Cervical metastases behavior of T1-2 squamous cell cancer of the oral mucosa.

The clinical management of the neck of patients with early-stage oral squamous cell cancer (OSCC) is still controversially discussed in the current literature. This study analyzes histo-clinical factors influencing the occurrence of cervical lymph node metastases (CM). In a retrospective mono-center study, patients with a primary T1-2 OSCC between 2000 and 2014 were analyzed regarding histo-clinical parameters possibly influencing the CM rate and the outcome. Two hundred eighty-five patients (66%) were male and 146 female (44%), with a mean age of 60±12years at the time of diagnosis. Seventy-seven percent showed a positive risk profile (nicotine/alcohol) and 69% underlying diseases. Forty-four percent of the patients were staged as T2 (30% with CM). Advanced tumor size (T1 vs. T2) and grading (G1-2 vs. G3) were statistically significantly (p<0.001) associated with the occurrence of CM. The localization within the oral cavity, age, gender, risk profile, or underlying diseases had no influence on CM occurrence. During the follow-up, tumor size (p=0.001), CM (p<0.001), and tumor relapse (p<0.001) were significantly associated with a worse outcome. Early-stage OSCC showed aggressive lymphatic metastatic behavior that depends on the size and the grading of the tumor. A watch-and-wait policy as the primary management for cN0 may likely be inferior to a selective neck dissection for this patient group and should only be considered for very small tumors with a good differentiation.

Overexpression of Suprabasin is Associated with Proliferation and Tumorigenicity of Esophageal Squamous Cell Carcinoma.

Suprabasin is a recently identified oncoprotein that is upregulated in multiple cancers. However, the clinical significance and biological role of suprabasin in human esophageal squamous cell carcinoma (ESCC) remains unclear. In the current study, we reported that suprabasin was markedly overexpressed in ESCC cell lines and tissues at both mRNA and protein levels, and this was associated with advanced clinical stage, tumor-nodes-metastasis (TNM) classification, histological differentiation, tumor size and poorer survival. Furthermore, we found that both proliferation and tumorigenicity of ESCC cells were significantly induced by suprabasin overexpression, but inhibited by suprabasin knock-down. Moreover, we demonstrated that upregulation of suprabasin activated the Wnt/β-catenin signaling pathway and led to nuclear localization of β-catenin and upregulation of Cyclin D1 and c-Myc. Together, our results suggest that suprabasin plays an important oncogenic role in promoting proliferation and tumorigenesis of ESCC.

Low expression of long noncoding RNA CASC2 indicates a poor prognosis and regulates cell proliferation in non-small cell lung cancer

Recently, long noncoding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. The aim of this study was to evaluate the expression and biological role of lncRNA CASC2 in non-small cell lung cancer (NSCLC). By bioinformatics analysis, we found that CASC2 was significantly decreased in NSCLC. qRT-PCR was performed to investigate the expression of CASC2 in tumor tissues and corresponding non-tumor NSCLC tissues from 76 patients. The lower expression of CASC2 was remarkably correlated with advanced TNM stage and tumor size. Multivariate analyses found that CASC2 expression served as an independent predictor for overall survival of NSCLC. Moreover, overexpression of CASC2 significantly inhibited NSCLC cell proliferation both in vitro and in vivo. In conclusion, our study demonstrated that CASC2 is involved in the development and progression of NSCLC and shows that CASC2 may be a potential diagnostic and target for new therapies in patients with NSCLC.