Small nucleolar RNAs (snoRNAs) play a crucial role during colorectal cancer (CRC) development. The study of SNORA71A is few, and its role in CRC is unknown. This study focused on screening abnormal snoRNAs in CRC and exploring the role of key snoRNA in CRC. The expression pattern of snoRNAs in 3 CRC and 3 normal colon tissues was detected via small RNA sequencing. The six candidate snoRNAs were identified by quantitative PCR (qPCR). Subsequently, the expression level of SNORA71A was further verified through the Cancer Genome Atlas (TCGA) data analysis and qPCR. The CCK8 and transwell assays were used to detect the functional role of SNORA71A in CRC cells. The integrated analysis of snoRNA expression profile indicated that a total 107 snoRNAs were significantly differentially expressed (DE) in CRC tissues compared with normal tissues, including 45 upregulated and 62 downregulated snoRNAs. Bioinformatics analysis revealed that the DE snoRNAs were mainly implicated in "detection of chemical stimulus involved in sensory perception of smell" and "sensory perception of smell" in the biological process. The DE snoRNAs were preferentially enriched in "olfactory transduction" and "glycosphingolipid biosynthesis-ganglio series pathway." The expression of SNORA71A was upregulated in CRC tissues and cells. SNORA71A expression showed statistically significant correlations with TNM stage (P = 0.0196) and lymph node metastasis (P = 0.0189) and can serve as biomarkers for CRC. Importantly, SNORA71A significantly facilitated the CRC cell proliferation, migration, and invasion. Our findings indicate that SNORA71A screened by sequencing acted as an oncogene and promoted proliferation, migration, and invasion ability of CRC cells.
Background: Mounting evidence has indicated that long noncoding RNAs (lncRNAs) are promising candidates for tumor diagnosis and prognosis.Nonetheless, the significance of lncRNAs in colorectal cancer (CRC) diagnosis remains to be clarified.Here, we performed a comprehensive meta-analysis to evaluate the utility of lncRNAs as diagnostic indicators for CRC.Materials and Methods: Pertinent studies were searched using PubMed, PMC, Web of Science, Cochrane, and EMBASE database up to September 2018.Study quality was assessed with the Quality Assessment for Studies of Diagnostic Accuracy-2.Subgroup analyses by sample size and publication year were conducted.Threshold effect and meta-regression were performed to find the origin of heterogeneity.Statistical analyses were conducted using Stata and Meta-Disc.Results: A total of 19 studies with 3,114 individuals were enrolled in the current analysis.The overall sensitivity and specificity of lncRNAs in the diagnosis of CRC were 0.83 [95% confidence interval (CI): 0.76-0.87]and 0.84 (95% CI: 0.77-0.89),respectively.The pooled positive likelihood ratio was 5.11 (95% CI: 3.57-7.31),and the pooled negative likelihood ratio was 0.21 (95% CI: 0.15-0.28).The overall area under the curve was 0.90 (95% CI: 0.87-0.92),with a diagnostic odds ratio of 24.57(95% CI: 14.67-41.17).Conclusions: The accuracy of lncRNAs for CRC diagnosis is high, and lncRNAs could be functioned as promising candidates for CRC diagnosis.
Purpose: This meta-analysis aimed to assess the prognostic value of long noncoding RNA cancer susceptibility candidate 2 (CASC2) in human tumors. Materials and methods: We searched the available databases up to December 2017. Pooled hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to examine the prognostic impact of CASC2 on overall survival (OS) in patients diagnosed with malignancies. Results: A total of eight studies with 663 cancer patients were enrolled. Our results showed that high CASC2 expression level was associated with a favorable OS (HR=0.437, 95% CI: 0.345-0.554). The significant results were not altered by stratified analysis according to cancer type, sample size, follow-up months, and HR estimation method. A significant association of glioma tumor stage with CASC2 expression was detected (III-IV vs I-II: odds ratio=2.126, 95% CI: 1.032-4.378). CASC2 could be used as an independent prognostic factor for OS (HR=0.450, 95% CI: 0.336-0.602). Sensitivity analysis showed that no single study changed the pooled results significantly. Begg's funnel plot and Egger's test showed that no publication bias was detected. Conclusion: High expression level of CASC2 is associated with favorable survival outcome for cancer patients, and CASC2 could be used as a prognostic predictor for cancers.
Deletion of the frequently mutated AT-rich interacting domain-containing protein 1A (ARID1A), an SWI/SNF subunit, is associated with poor prognosis in various tumors. This study observed and analyzed ARID1A expression and its correlation with prognosis in gastric carcinoma. Postoperative sections of 98 patients with primary gastric cancer and 40 patients with gastric benign lesions were examined by immunohistochemistry. ARID1A deficiency was observed in 19.39% of gastric cancer tissues, 4.08% of matched paracancerous tissues, and 2.5% of normal gastric mucosa tissues. ARID1A expression was significantly down-regulated in gastric cancer tissues compared with paracancerous tissues (P = .001) and normal gastric mucosa tissues (P = .011). ARID1A deletion significantly correlated with tumor size (P = .022), lymph node metastasis (P = .030), and tumor differentiation (P = .009). In the 90 gastric cancer tissues with tumor stages II and III, the clinical outcome of the ARID1A-negative patients was significantly poorer than that of the ARID1A-positive patients (P = .005). Univariate analysis revealed that tumor invasion depth (P = .025), stage (P = .032), poor differentiation (P = .046), lymph node metastasis (P = .038), and ARID1A expression (P = .023) were significantly related to the overall survival of gastric cancer patients. Multivariate analysis demonstrated that tumor invasion depth (P = .029) and ARID1A expression (P = .031) were independent factors that indicate poor prognosis. In conclusion, the loss of ARID1A expression in gastric cancer patients significantly correlated with poor survival.
INTRODUCTION:CD146 is a membrane signal receptor in tumor-induced angiogenesis. However, limited studies have focused on the CD146 promoter polymorphisms in clear cell renal cell carcinoma (ccRCC).PURPOSE:The purpose of this study was to investigate the association between polymorphisms located in the promoter region of the CD146 gene and characteristics of ccRCC in Chinese population. The association between the CD146 promoter polymorphisms and CD146 expression was also investigated in ccRCC.MATERIALS AND METHODS:A total of 600 samples including 300 ccRCC patients and 300 healthy controls were collected for analysis of the CD146 promoter polymorphisms by direct sequence. The CD146 expressions were measured by qRT-PCR.RESULTS:We had not found any significant differences in genotypic and allelic frequencies of CD146 promoter polymorphisms between ccRCC patients and controls. The rs3923594 was associated with stage and metastasis (300 cases) and recurrence (263 cases) of ccRCC in Chinese population. A significant association was also observed between the rs3923594 and CD146 expression (227 cases) in ccRCC.CONCLUSIONS:CD146 promoter polymorphisms were not associated with the risk of ccRCC in Chinese population. The rs3923594 was an independent predictor of recurrence in Chinese patients with localized ccRCC.
ObjectiveTo explore the expression of PinX1 protein in colorectal cancer (CRC) tissues and its clinical significance.Methods A total of 83 paired CRC specimens and their adjacent normal tissues were collected, all of the patients received 4-6 cycles of 5-fluorouracil (5-Fu) based adjuvant chemotherapy. PinX1 protein expression was analyzed by immunohistochemical staining, its correlations with clinicopathological factors and prognosis were further evaluated.Results PinX1 expression was decreased in 36 tumor tissues (43.4%), while only decreased in 8 adjacent normal tissues (9.6%), which was statistically significant (P<0.001). Although no correlations with clinicopathological features, PinX1 downregulation was significantly associated with adverse 5-year overall survival (OS) and disease-free survival (DFS).Conclusion PinX1 protein expression is decreased in CRC, which may be a new promising tumor marker for CRC prognosis and 5-FU chemosensitivity.
An increasing body of evidence suggests that ribosomal proteins may have ribosome-independent functions and may be involved in various physiological and pathological processes. To examine the role of ribosomal protein L34 (RPL34) in cancer transformation, we assessed its expression in gastric cancer cell lines and found it highly expressed. We further used lentivirus-mediated small interfering RNAs (siRNAs) to knockdown RPL34 expression in the human gastric cancer cell line SGC-7901. RNA interference (RNAi)-mediated inhibition of RPL34 expression in SGC-7901 cells significantly suppressed cell proliferation, increased apoptosis and arrested cells in the S phase. The results of the present study suggest that RPL34 plays a critical role in cell proliferation, cell cycle distribution and apoptosis of human malignant gastric cells.
BACKGROUND:The aim of this meta-analysis was to analyze the relationship of toxicities and clinical benefits of newly approved lenvatinib and sorafenib to thyroid cancer (TC) in patients.MATERIALS AND METHODS:Three major medical databases, PubMed, EMBASE, and ISI web of science were systematically searched to identify all studies on lenvatinib and sorafenib in TC. A meta-analysis was performed to clarify the toxicities and clinical benefits of newly Food and Drug Administration (FDA) approved lenvatinib and sorafenib to thyroid cancer.RESULTS:Ten studies (n = 749) were included which evaluated the toxicities and clinical benefits of newly FDA approved lenvatinib and sorafenib to thyroid cancer. 537 (71.7%) of the 749 patients bearing TC (radioiodine-refractory, differentiated thyroid cancer) clinical benefits from lenvatinib or sorafenib, and serious adverse events occurred in 430 (57.4%) of the 749 patients ([risk ratio (RR) = 1.27, 95% confidence interval (CI) = (1.05-1.53), P = 0.01]). While 31 (4.1%) of the 749 patients died due to various reasons, that mainly accounts for severe bleeding events and cardiac arrest. The clinical benefit is obvious compared to deaths ([RR = 17.06, 95% CI = (12.08-24.11), P < 0.001]). Subgroup analyses were then conducted according to cancer type (radioiodine-refractory thyroid cancer [RR-TC] and TC). We found that in treating RR-TC, the clinical benefits are close to toxicities. While in treating TC, the clinical benefits are better than toxicities. And we found that sorafenib and lenvatinib might be proper to deal with TC (benefits rate 79.7%) compared to RR-TC (benefits rate 69.5%), taking consider of toxicities.CONCLUSIONS:Lenvatinib and sorafenib are useful in the treatment of TC. Although, their toxicities remain high (57.4%) in the patients, the death rate is controlled (4.1%). Take consider of toxicities, lenvatinib, and sorafenib are more useful for TC compared to RR-TC.
Purpose . To investigate promoter methylation in the deleted in lung and esophageal cancer 1 ( DLEC1 ) gene in Chinese patients with gastric cancer. Methods . A total of 227 patients with gastric cancer were enrolled. The methylations of the promoter regions of DLEC1 and ACTB were determined using quantitative methylation-specific PCR. The DLEC1 methylation was compared to the clinicopathological variables of gastric cancer. Results . DLEC1 methylation was not associated with the clinicopathological variables of gastric cancer. Patients with DLEC1 -hypermethylated gastric cancer had significantly higher recurrence rate than those with DLEC1 -hypomethylated gastric cancer (P=0.025;hazard ratio=2.43). Conclusions . Methylation of DELC1 promoter may be a valuable predictor for recurrence in Chinese patients with gastric cancer.
The objective of this study was to investigate the association of serum cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels with clinicopathological parameters in patients diagnosed with metastatic breast cancer (MBC). We retrospectively evaluated the medical records of 284 patients diagnosed with MBC between January, 2007 and December, 2012 who fulfilled the specified criteria and the association between the levels of the two tumor marker and clinicopathological parameters was analyzed. Of the 284 patients, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were identified in 163 (57.4%) and 97 (34.2%) patients, respectively. Elevated CA 15-3 and CEA levels were significantly associated with breast cancer molecular subtypes (P<0.001 and P=0.032, respectively). Cases with luminal subtypes exhibited a higher percentage of elevated CA 15-3 and CEA levels compared to non-luminal subtypes. Elevated CA 15-3 level was correlated with bone metastasis (P=0.017). However, elevation of CEA was observed regardless of the site of metastasis. Elevation of CA 15-3 was significantly more common in MBC with multiple metastatic sites compared to MBC with a single metastasis (P=0.001). However, the incidence of elevated CEA levels did not differ between patients with a single and those with multiple metastatic sites. In conclusion, elevated CA 15-3 and CEA levels at initial diagnosis of recurrence were found to be associated with breast cancer molecular subtypes, whereas an elevated CA 15-3 level was significantly correlated with bone metastasis and an elevated CEA level was observed regardless of metastatic site. The proportion of MBC cases with elevated CA 15-3 levels differed according to the number of metastatic sites.
The intercellular adhesion molecule-1 (ICAM1) has been reported to function in multiple malignancies, but its effect on clear cell renal cell carcinoma (ccRCC) hasn't been discussed yet. This study aimed to identify the potential role of ICAM1 in prognostic prediction and early diagnosis of ccRCC. ICAM1 expression was inspected by immunohistochemistry and correlated with clinicopathologic variables. Association between protein expression and cancer-specific survival (CSS) of ccRCC patients was evaluated and the value of area under the receiver operating characteristics (ROC) curve (AUC) was calculated to measure the protein's diagnostic accuracy. ICAM1 was positively immunostained in 83.2% of 173 ccRCC tissues, but negatively immunostained in all the para-cancerous normal epitheliums of renal tubules. High ICAM1 expression was significantly related to male sex (P = 0.00241), T3/T4 stage (P = 0.02249), non-N0M0 stage (P = 0.03797) and positive renal pelvis invasion (P = 0.04227). Kaplan-Meier survival analysis illustrated that high ICAM1 expression was significantly correlated to a decreased CSS (P = 0.00006). Multivariate Cox analysis indicated that ICAM1 was an independent predictor for CSS of patients (P = 0.00451). Furthermore, the AUC value of ICAM1 in diagnosing ccRCC was 0.916 (P < 0.00001). In conclusion, high ICAM1 expression on tumor cells indicates a poor outcome of patients and ICAM1 is likely to be an independent predictor for the prognosis of ccRCC. Moreover, ICAM1 has a high AUC value and may be a potential and useful diagnostic marker.
PURPOSE:The objective of this study is to determine whether or not plasma cfDNA levels can predict efficacy of sorafenib in patient with metastatic cRCC.MATERIALS AND METHODS:Plasma cfDNA levels were quantified by quantitative real-time PCR at six different time-points (before treatment, 4 weeks, 8 weeks, 12 weeks, 16 weeks, and 24 weeks) in 18 metastatic cRCC patients receiving sorafenib, as assessed by CT examination according to RECIST 1.1.RESULTS:A significantly lower plasma cfDNA level, measured from 8 weeks to 24 weeks, was found in patients with remission or stable disease than in those with progression. Higher levels in plasma cfDNA levels during the course of treatment indicated poor outcome. For predicting progression, a sensitivity of 66.7% was achieved at 100% specificity using cfDNA levels at 8 weeks.CONCLUSIONS:Monitoring of plasma cfDNA levels during the course of sorafenib therapy could identify metastatic cRCC patients who are likely to exhibit a poor response at an early stage.