Increase In Clinical Stage Research Articles

Clinical Care Pathway Time Intervals and Tumor Progression Among Head and Neck Cancer Patients at East Avenue Medical Center Before and During the COVID-19 Pandemic

Objective: To investigate the association between the time intervals of key clinical time points and tumor progression (increase in clinical staging) in head and neck cancer patients before and during the pandemic. Methods: Design: Retrospective Cohort Study Setting: Tertiary Government Training Hospital Participants: A total of 81 head and neck cancer patients who consulted at the OPD and underwent elective surgery between January 1, 2018, and December 31, 2022, under the Department of Otorhinolaryngology – Head and Neck Surgery of East Avenue Medical Center were included in the study; 40 patients comprised the pre-pandemic group and 41 patients-the pandemic group. Results:Majority of patients were men (61.73%), and the mean age was 54 years. The most prevalent tumor site was the oral cavity (37.04%). Most patients were Clinical Stage IV at the time of diagnosis (32.10%) and at the time of surgery (58.02%). In the pre-pandemic period, median time-to-consult was 180 days, time-to-diagnosis was 14 days, and time-to-treatment was 57 days. During the pandemic, median time-to-consult significantly increased to 365 days (Mann-Whitney test, U = 589, p = .028), but time-to-diagnosis decreased to 10 days, and time to-treatment decreased to 43 days, although these were not significant (U = 775, p = .667; U = 809, p = .917). Among the 81 patients in the study, 14 (17.28%) showed tumor progression (pre-pandemic: 6; 15%; pandemic: 8; 19.51%), but there was no significant association between time-to-consult and increase in clinical staging for both pre-pandemic (χ2(38) = 34.2, p = .646) and pandemic groups (χ2(16) = 23.1, p = .110) or between time-to-diagnosis and increase in clinical staging for pre-pandemic (χ2(56) = 36.8, p = .978) and pandemic groups (χ2(23) = 28.3, p = .267). Overall, there was no significant association between time-to-treatment and increase in clinical staging for both pre-pandemic (χ2(62) = 80.00, p = .062) and pandemic groups (χ2(32) = 30.4, p = .548), but a subset of patients with larynx primary tumor site had a statistically significant association between time-to-treatment and tumor progression (χ2(5) = 12.00, p = .035). Conclusion:This study revealed that there was an increase in time to-consult for head and neck cancer patients during the pandemic. However, there was no significant difference in time-to-diagnosis and time-to-treatment. This shows that the Department of ORL-HNS, East Avenue Medical Center has provided pandemic head and neck cancer care similar to before the pandemic. No significant associations were found between tumor progression and time intervals of the key clinical time points but patients who had an increase in clinical stage were noted with longer time-to treatment. It was also observed that more patients were in advanced clinical stages during the pandemic.

LPCAT1 acts as an independent prognostic biomarker correlated with immune infiltration in hepatocellular carcinoma

BackgroundLysophosphatidylcholine acyltransferase 1 (LPCAT1) is overexpressed in multiple human tumors. However, the role of LPCAT1 in hepatocellular carcinoma (HCC) has not been understood. We aim to explore the relationships between LPCAT1 expression and prognosis, clinicopathological features, tumor microenvironment (TME), immune cell infiltration, immune checkpoint gene expression, and related signaling pathways in HCC. Furthermore, we also explored the relationship between LPCAT1 expression and drug sensitivity to HCC treatment.MethodsThe expression profiles were acquired from the Cancer Genome Atlas (TCGA) and the Human Protein Atlas (THPA). Immune status and infiltration in cancer tissues were explored using the single sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithm.ResultsLPCAT1 was overexpressed in HCC, and its expression was related to poor prognosis, LPCAT1 was an independent prognostic biomarker in HCC. Expression of LPCAT1 increased statistically with the increase of clinical stage and grade of HCC patients. GO and KEGG network analysis revealed that LPCAT1 positively associated molecules were mostly enriched in functions related to cell adhesion. The TME score of high-LPCAT1 group was significantly higher than that of low-LPCAT1 group. Immune infiltrating cells positively correlated with LPCAT1 expression were Macrophages M0, B cells memory, Dendritic cells activated, T cells regulatory and T cells gamma delta in HCC. We found a positive correlation between LPCAT1 and most immune checkpoint gene expression. The IC50 of 5-Fluorouracil, Gemcitabine, Mitomycin C, Sorafenib and Cabozantinib in patients with high-LPCAT1 expression was lower than that in patients with low-LPCAT1 expression. Our findings provide a wealth of information for further understanding of the biological functions and signaling pathways of LPCAT1 in HCC.ConclusionsLPCAT1 is an independent prognostic biomarker and associated with tumor microenvironment, immune cell infiltration, immune checkpoint expression and drug sensitivity in hepatocellular carcinoma.

189: THE EFFECT OF COVID -19 ON THE NEW DIAGNOSIS OF ESOPHAGOGASTRIC CANCER IN THE UK: A SINGLE-CENTRE EXPERIENCE

Abstract Background and aim Covid-19 has had a devastating global impact and resulted in over 4.4 million directly attributed deaths. The UK entered lockdown in March 2020, redistributing its medical workforce and resources. Early estimations suggested at least 4700 extra cancer deaths at 5 years if there was a 3-month delay to surgery. Delays to diagnosis and treatment for esophagogastric (EG) cancers can be particularly detrimental to survival. The aim of this study is to assess the impact of Covid-19 on new cancer referrals to a centralised UK EG cancer centre, including presentation, decision making and treatment. Methods Patients with EG cancer referred to a tertiary, high-volume centre between March 2019 and March 2021 were reviewed. Patients were stratified into Pre-covid (March 2019–March 2020) and Covid (March 2020–2021) cohorts. Number of new referrals, clinical stage, treatment decision, and time to treatment were compared for gastric adenocarcinoma (GA), esophagogastric-junction adenocarcinoma (EGJA), esophageal adenocarcinoma (EA) and esophageal SCC (ESCC). Results There was an 11% reduction in new cancer referrals (485 vs 431). GA, EGJA and EA did not have significant change in treatment intent, although there was a significant increase in the decision for definitive non-surgical treatment of EA (P = 0.046). GA and EA patients had a small, but significant increase in average clinical stage at presentation (P < 0.05). There was no increase in time to treatment for GA, EGJA and EA. A significantly higher proportion of ESCC patients were given curative intent treatment in the Covid-19 cohort (P = 0.0006) however, this was accompanied with an increased time to treatment (35.8 days vs 27.9 days P = 0.0198). Conclusion This high-volume centre has seen a reduction in new cancer referrals since the first UK lockdown. This was associated with a small, but significant, increase in clinical stage of GA and EA at presentation. This may represent an early indication of excess esophagogastric cancer deaths due to the impact of Covid-19. This data also confirms initial results showing that oncological decisions were not compromised, although Covid-19 remains a dynamic challenge.

Analysis of levels and Clinical value of CA19-9, NLR and SIRI in patients with Pancreatic Cancer with different Clinical Features.

This study aimed to investigate the levels of cancer antigen 19-9 (CA19-9), neutrophil/lymphocyte ratio (NLR) and systemic immune-inflammatory index (SIRI) in patients with pancreatic cancer with different clinical features and their clinical value. For this purpose, 78 patients with pancreatic cancer treated in our hospital from January 2018 to January 2021 were divided into two groups according to the NLR and SIRI calculated by blood routine and biochemical examination before operation. To observe and analyze the relationship between serum CA19-19 levels, clinical features and NLR and SIRI values in patients with different clinical stages and tumor diameter, and the diagnostic value of CA19-9, NLR and SIRI in pancreatic cancer. The results showed that the level of serum CA19-9 in patients with stage IV pancreatic cancer was significantly higher than that in patients with stage I, II and III, and the level of CA19-9 in patients with stage III was higher than that in patients with stage I and II, and the level of CA19-9 in patients with stage II was higher than that in patients with stage I. The level of CA19-9 in patients with pancreatic cancer with tumor diameter ≥ 5cm was significantly higher than that in patients with tumor diameter < 5cm. The percentage of patients with age ≤ 60 years old in high NLR group (83.78%) was significantly higher than that in low NLR group (63.41%), and the rate of patients with tumor diameter ≥ 5cm in the high SIRI group (54.05%) was significantly higher than that in low NLR group (26.83%). The rate of patients with tumor diameter ≥ 5cm in the high SIRI group (61.92%) was significantly higher than that in the low SIRI group (31.58%). Among the single indexes, the sensitivity of CA19-9 in the diagnosis of pancreatic cancer was the highest (93.10%). The specificity of Siri in the diagnosis of pancreatic cancer was 89.70%. The sensitivity and specificity of combined detection were 89.7% and 70.00%, respectively. In general, the level of serum CA19-9 in patients with pancreatic cancer increases gradually with the increase of clinical stage and tumor diameter. NLR value is related to patient age and tumor diameter, and SIRI value is related to tumor diameter. Combined detection of CA19-9, NLR and SIRI are of higher value in the early diagnosis of pancreatic cancer.

P-OGC80 The effect of COVID -19 on new diagnosis oesophagogastric cancer patients in the UK: A single-centre experience

BackgroundCovid-19 has had a devastating global impact and resulted in over 4.4 million directly attributed deaths. The UK entered lockdown in March 2020, redistributing its medical workforce and resources. Early estimations suggested at least 4700 extra cancer deaths at 5 years if there was a 3-month delay to surgery. Delays to diagnosis and treatment for osophagogastric (OG) cancers can be particularly detrimental to survival. The aim of this study is to assess the impact of Covid-19 on new cancer referrals to a centralised UK OG cancer centre, including presentation, decision making and treatment. MethodsPatients with OG cancer referred to a tertiary, high-volume centre between March 2019 and March 2021 were reviewed. Patients were stratified into Pre-covid (March 2019-March 2020) and Covid (March 2020-2021) cohorts. Number of new referrals, clinical stage, treatment decision, and time to treatment were compared for gastric adenocarcinoma (GA), oesophagogastric-junction adenocarcinoma (OGJA), oesophageal adenocarcinoma (OA) and oesophageal SCC (OSCC).ResultsThere was an 11% reduction in new cancer referrals (485 vs 431). GA, OGJA and OA did not have significant change in treatment intent, although there was a significant increase in the decision for definitive non-surgical treatment of OA (P = 0.046). GA and OA patients had a small, but significant increase in mean clinical stage at presentation (P < 0.05). There was no increase in time to treatment for GA, OGJA and OA. A significantly higher proportion of OSCC patients were given curative intent treatment in the Covid-19 cohort (P = 0.0006) however, this was accompanied with an increased time to treatment commencement (35.8 days vs 27.9 days P = 0.0198). ConclusionsThis high-volume centre has seen a reduction in new cancer referrals since the first UK lockdown. This was associated with a small, but significant, increase in clinical stage of GA and OA at presentation. This may represent an early indication of excess oesophagogastric cancer deaths due to the impact of Covid-19. This data also confirms initial results showing that oncological decisions were not compromised, although Covid-19 remains a dynamic challenge.

Frailty is associated with increased risk of cirrhosis disease progression and death.

The Liver Frailty Index (LFI) is a well-studied tool that evaluates frailty in patients with cirrhosis. Consisting of grip strength, chair stands, and balance testing, the LFI has been associated with increased mortality in patients awaiting liver transplant. We aimed to extend our understanding of frailty in cirrhosis by exploring the relationship between the LFI and the risk of (1) cirrhosis progression, (2) mortality, and (3) unplanned hospitalizations, in both compensated and decompensated disease. Adult patients with cirrhosis from four centers in North America and one in India were included. Frailty was measured at baseline using the LFI and categorized as robust (LFI < 3.2), prefrail (LFI 3.2-4.5), and frail (LFI > 4.5). Progression of cirrhosis was defined by an increase in clinical stage, ranging from 1 to 5, from baseline using the D'Amico classification. Factors associated with progression, mortality, and hospitalizations were evaluated using multivariate regression models, with transplant as a competing risk. In total, 822 patients with cirrhosis were included. Average Model for End-Stage Liver Disease (MELD) score was 15.5±6.0. In patients with compensated cirrhosis, being frail versus robust was associated with increased risk of progression to the next cirrhosis stage or to death (HR, 2.45; 95% CI, 1.14-5.29) and with an increased risk of unplanned hospitalizations (2.32; 95% CI, 1.13-4.79), after adjusting for age, sex, and MELD score. Similar HRs were observed in patients with decompensated cirrhosis. Frailty was an independent predictor of cirrhosis progression or death and unplanned hospitalization across patients with compensated and decompensated cirrhosis. Future studies are needed to evaluate the possibility of slowing cirrhosis disease progression by reversing or preventing frailty.

The Oncogenic Role of APC/C Activator Protein Cdc20 by an Integrated Pan-Cancer Analysis in Human Tumors.

The landscape of CDC20 gene expression and its biological impacts across different types of cancers remains largely unknown. Here, a pan-cancer analysis was performed to analyze the role of Cdc20 in various human cancers. Our results indicated that the expression levels of the CDC20 gene were significantly elevated in bladder cancer, breast cancer, colon cancer, rectum cancer, stomach cancer, esophageal cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, prostate cancer, pancreatic cancer, and uterine cancer. In addition, the expression of CDC20 was significantly and positively correlated with the increase of clinical stages in multiple cancer types, including breast cancer, kidney cancer, and lung cancer, et al. Among 33 cancer subtypes in the TCGA dataset, the high expression of CDC20 was correlated with poor prognosis in 10 cancer types. Furthermore, the abundance of phosphorylated Cdc20 in the primary tumor was elevated and correlated with increased tumor grade. Next, we sought to elucidate the oncogenic role by analyzing its association with immune infiltration. For most cancer types, the CDC20 expression was positively correlated with the infiltration of cancer-associated fibroblasts and myeloid-derived suppressor cells. To further understand its functional activity, we explored the classic Cdc20 downstream substrates, which were found to be mutually exclusive with the expression of Cdc20. Moreover, the pan-cancer analysis of the molecular function of Cdc20 indicated that BUB1, CCNA2, CCNB1, CDK1, MAD2L1, and PLK1 might play a critical role in interaction with Cdc20. The abundance of Cdc20 was further validated at transcriptional and translational levels with a publicly available dataset and clinical tumor tissues. The knockdown of Cdc20 dramatically inhibited tumor growth both in vivo and in vitro. Therefore, our studies delineated the oncogenic role of CDC20 and its prognostic significance at the pan-cancer level and proved its functional activity in Cdc20 high expression cancer types. Our studies will merits further molecular assays to understand the potential role of Cdc20 in tumorigenesis and provide the rationale for developing novel therapeutic strategies.

Exploration of the Expression of Circulating miRNA in Serum of Patients with Prostate Cancer

To explore the value of circulating micro ribonucleic acid expression in serum in the diagnosis of prostate cancer, this paper used The Cancer Genome Atlas database to download prostate cancer related datasets, analyze the expression of circulating micro ribonucleic acids in serum of prostate cancer tissues, screen differentially expressed micro ribonucleic acids, and find that micro ribonucleic acid-141 is significantly different. Then select 30 patients with prostate cancer in urology, and 20 patients with benign prostatic hyperplasia in the same period as research subject. The control group was 20 healthy subjects in the same period. The expression of serum micro ribonucleic acid-141 in control group, benign prostatic hyperplasia group and prostate cancer group was detected by fluorescent quantitative Polymerase Chain Reaction, and the content of total prostate specific antigen before treatment in prostate cancer group. The results showed that the expression level of serum micro ribonucleic acid-141 in the prostate cancer group was (11.2±8.1) times higher than that in the control group, which was significantly higher than that in the benign prostatic hyperplasia group (1.65+1.73) and the control group. The difference was statistically significant (p<0.05). The expression level of serum micro ribonucleic acid-141 in prostate cancer group was positively correlated with total prostate specific antigen level, correlation coefficient r=0.753, statistically significant (p<0.05). Serum micro ribonucleic acid-141 expression level is associated with Gleason score, clinical stages and occurrence of metastasis. With the increase of clinical stage, the expression level of micro ribonucleic acid increased. It is concluded that serum circulating micro ribonucleic acid-141 can be used as a molecular indicator for the diagnosis of prostate cancer.

Study on the Expression and Significance of P16 Gene Methylation Based on Information Technology Statistics in Female Cervical Cancer in Hunan Povince

To explore the significance of p16 gene methylation and abnormal expression in cervical cancer, Methylation specific PCR (MSP) was used to detect 5 ′ CpG island methylation of p16 gene promoter in 60 cervical cancer tissues of different pathological types and clinical stages, who was chosen in Human province. Detection of homozygous deletion of exon 1 (E1) and exon 2 (E2) of p16 gene by PCR. Immunohistochemical analysis of p16 protein expression. The results showed that there was no methylation of p16 gene in normal control tissues and paracancerous tissues and no E1 and E2 deletions and abnormal p16 protein expression were found. The methylation rate of 60 cervical cancer samples was 21.67% (13 / 60), the deletion rate of p16 gene was 15.00% (9 / 60), and the expression rate of p16 protein was 51.67% (31 / 60). It can be seen that the positive expression rate of p16 gene protein decreased with the increase of clinical stage. The results suggest that p16 gene inactivation is common in cervical cancer and closely related to the pathological grade. p16 gene methylation plays a role in the development of cervical cancer.

Discovery and characteristics of B cell-like T cells: A potential novel tumor immune marker?

BackgroundCD3 and CD19 are the characteristic surface markers of mature T lymphocytes and B lymphocytes of human respectively. A special subset of immune cells that characteristically expressed the surface markers CD19+ of B lymphocytes and CD3+ of T lymphocytes simultaneously (CD19+CD3+ cells, hereinafter referred to as B-T cells) was found in the peripheral blood of human, yet it has not been reported in cancer research before. Our aims were to characterize the expression and possible value of B-T cells in cancer patients. MethodsFlow cytometry was applied to analyse the CD19+CD3+ cells, and laser scanning confocal microscope was utilized to prove co-expressing CD19+ of B lymphocytes and CD3+ of T lymphocytes simultaneously on the surface of the cells. Then a total of 523 patients with malignant tumor were enrolled in this study, and 177 healthy donors were recruited as the control group. The levels of CD19+CD3+ cells in peripheral blood were measured by flow cytometry, and the differences between the two groups were compared. ResultsThe healthy donors and cancer patients all had B-T cells in their peripheral blood, but the percentage of B-T cells was 0.16 % ± 0.11 % and 0.58 % ± 0.38 % respectively, showing statistically significant (P < 0.0001). There was no significant correlation between the percentage of B-T cells and lymphocyte subsets (P > 0.05). The percentages of B-T cells in different tumor species were different. The proportion of B-T cells was high in esophageal cancer, non-Hodgkin's lymphoma and lung cancer, but it was low in pancreatic cancer, ovarian cancer and kidney cancer. Meanwhile, there was significant difference between esophageal cancer and kidney cancer (P < 0.001). The distribution of B-T cells in pancreatic cancer and kidney cancer was more concentrated, yet more dispersed in other cancers. Although there was a trend of increase in clinical stage Ⅲ+Ⅳ and a trend of decrease in age above 60 years for breast cancer, gastric cancer and liver cancer, there was no significant difference in the percentage of B-T cells in age, gender, different clinical stages, tumor metastasis, lymph node metastasis, and splenomegaly (P > 0.05). ConclusionThe percentage of B-T cells in cancer patients was significantly higher than that of healthy donors. B-T cells maybe play a very complicated role in tumor, whether it could be a potential tumor immune marker or not and what are the specific phenotypes and functions of it to need be further verified.

Long noncoding RNA MACC1-AS1 is a potential sponge of microRNA-34a in cervical squamous cell carcinoma and upregulates cyclin-dependent kinase 6.

The present study aimed to investigate the role of long noncoding RNA MACC1-AS1 in cervical squamous cell carcinoma (CSCC). In the present study MACC1-AS1 expression as analyzed using reverse transcription-quantitative PCR. The interactions between MACC1-AS1 and miR-34a was analyzed via overexpression experiments. Cell cycle and proliferation analyses were performed to analyze the roles of MACC1-AS1 in regulating cancer cell cycle progression and cell proliferation. It was observed that MACC1-AS1 was upregulated in CSCC, and its expression levels were elevated with the increase in clinical stage. Bioinformatics analysis revealed that MACC1-AS1 may be a sponge of miR-34a, which can target cyclin-dependent kinase 6 (CDK6). In CSCC cells, MACC1-AS1 overexpression led to upregulation of CDK6, while miR-34a overexpression had the opposite effect and reduced the effects of MACC1-AS1 overexpression in co-transfected cells. Cell cycle and proliferation analyses demonstrated that MACC1-AS1 and CDK6 promoted cell cycle progression and cell proliferation. By contrast, miR-34a had the opposite effect on cell cycle proliferation and cell proliferation, reducing the effects induced by MACC1-AS1 overexpression. Therefore, the lncRNA MACC1-AS1 may serve as a sponge of miR-34a to upregulate CDK6, thereby promoting cell cycle progression and cell proliferation.

The role of MMP-2 and MMP-9 in the metastasis and development of hypopharyngeal carcinoma

IntroductionThe role of matrix metalloproteinase-2 and 9 in the metastasis and development of hypopharyngeal carcinoma has not been clarified. ObjectivesTo observe the relationship between matrix metalloproteinase-2, matrix metalloproteinase-9 and the metastasis, development of hypopharyngeal carcinoma. MethodsThis study included 42 hypopharyngeal cancer patients. The mRNA and protein expression levels of matrix metalloproteinase-2 and 9 in hypopharyngeal carcinoma and paracancerous tissues were detected by reverse transcription-polymerase chain reaction and Western blot. ResultsReverse transcription-polymerase chain reaction detection showed that the mRNA of matrix metalloproteinase-2 and 9 was expressed in both cancer and pericarcinoma tissues, but was almost not expressed in polypoid control tissues. The expression intensity in the cancer tissue was significantly higher than that in the pericarcinoma tissue (matrix metalloproteinase-2: t ＝ 2.529, p = 0.015; matrix metalloproteinase-9: t ＝ 4.781, p ＜ 0.001). The mRNA expression in the cancer tissue was enhanced with the increase of the tumor clinical stage (matrix metalloproteinase-2: F = 4.003, p = 0.026; matrix metalloproteinase-9: F = 5.501, p = 0.008). Its expression intensity was associated with the metastasis of lymph nodes (N staging) and increased with the degree of lymphatic metastasis (matrix metalloproteinases-2: F = 8.965, p = 0.005; matrix metalloproteinase-9: F = 5.420, p = 0.025). There was no significant change in T staging of tumor. With the increase of tumor pathological stage, the mRNA expression of matrix metalloproteinase-2 and 9 was strengthened (matrix metalloproteinase-2: F = 3.884, p = 0.029; matrix metalloproteinase-9: F = 3.783, p = 0.032). The protein expression level of matrix metalloproteinase-2 and 9 was the same as that of mRNA. ConclusionThe expression of matrix metalloproteinase-2 and 9 in hypopharyngeal carcinoma was significantly higher than that in pericarcinoma tissue, and it was enhanced with the increase of clinical stage. The expression level was related to lymph node metastasis and tumor pathological stage. Thus, matrix metalloproteinase-2 and 9 may be involved in the occurrence, development, invasion and metastasis of hypopharyngeal carcinoma through a variety of mechanisms.

Identification of Potentially Functional CircRNA-miRNA-mRNA Regulatory Network in Gastric Carcinoma using Bioinformatics Analysis.

BackgroundAs all we know, gastric cancer (GC) is a highly aggressive disease. Recently, circular RNA (circRNA) was found to play a vital role in regulation of GC. Some circRNAs could regulate messenger RNA (mRNA) expression by functioning as a microRNA (miRNA) sponge. Nevertheless, the circRNA-miRNA-mRNA regulatory network involved GC rarely has been explored and researched.Material/MethodsAll the differentially expressed circRNAs, miRNAs, and mRNA were derived from Gene Expression Omnibus (GEO) microarray data (GSE78092, GSE89143, GSE93415, and GSE54129). GC level 3 miRNA-sequencing data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Furthermore, a circRNA-miRNA-mRNA regulatory network was constructed by Cytoscape (version 3.6.1). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway revealed the functions and signaling pathways associated with these target genes. Hub genes of protein-protein interaction (PPI) network were identified by STRING database and cytoHubba.ResultsThe regulatory network consists of 3 circRNAs, 22 miRNAs, and 128 mRNAs. Only 3 miRNAs of the network were consistent with the expression of TCGA and were associated with some clinical features. The results of the functional analysis of 128 mRNAs showed that GO analysis and KEGG pathways of inclusion criteria were 49 and 24, respectively. PPI network and Cytoscape showed that the top 10 hub genes were MYC, CTGF, TGFBR2, TGFBR1, SERPINE1, KRAS, ZEB1, THBS1, CDK6, and TNS1; 4 of which were verified by GEPIA based on TCGA. Highly expressed SERPINE1 had a poor OS (over survival) and DFS (disease-free survival), and TGFBR1 expression increased along with the increase of clinical stages.ConclusionsThis study looked at a circRNA-miRNA-mRNA regulatory network associated with GC and explored the potential functions of mRNA in the network, then identified a new molecular marker for prediction, prognosis, and therapeutic targets for clinical patients.

LncRNA NBR2 suppresses migration and invasion of colorectal cancer cells by downregulating miRNA-21.

It has been reported that lncRNA NBR2 regulates cancer metabolism. We investigated the role of NBR2 in colorectal cancer. We found that NBR2 was downregulated in colorectal cancer tissues than in adjacent healthy tissues. Decreased expression levels of NBR2 in tumor tissues were observed with the increase of clinical stages. MiRNA-21 was upregulated in colorectal cancer tissues than in adjacent healthy tissues, and was significantly and inversely correlated with NBR2. NBR2 overexpression downregulated miRNA-21 in colorectal cancer cells, while miRNA-21 overexpression failed to significantly affect NBR2 expression. NBR2 overexpression suppressed migration and invasion of colorectal cancer cells. MiRNA-21 overexpression played an opposite role and attenuated the effects of NBR2 overexpression. NBR2 overexpression did not significantly alter cancer cell proliferation. Therefore, lncRNA NBR2 inhibited colorectal cancer cell migration and invasion possibly by downregulating miRNA-21.

LncRNA GATA6-AS inhibits cancer cell migration and invasion in gallbladder cancer by downregulating miR-421.

BackgroundLong non-coding RNS (lncRNA) GATA6-AS regulates endothelial cell growth, which is involved in many types of human diseases.PurposeOur study was carried out to investigate the involvement of GATA6-AS in gallbladder cancer (GBC).Patients and methodsSixty-two patients with GBC were recruited in this study. PCR analysis was performed to determine the expression of GATA6-AS, miR-421 and TIMP-2 in tissues or cell lines. Transwell migration and invasion assay was applied.ResultsWe found that GATA6-AS was downregulated in tumor tissues than in adjacent healthy tissues of GBC patients, and GATA6-AS expression levels in tumor tissues decreased with the increase of clinical stages. MiR-421 was upregulated in tumor tissues than in adjacent healthy tissues of GBC patients and was inversely correlated with the expression levels of GATA6-AS. MiR-421 overexpression failed to significantly affect GATA6-AS in GBC cells, while GATA6-AS overexpression resulted in inhibited miR-421 expression. GATA6-AS overexpression led to decreased migration and invasion rates of GBC cells. MiR-421 overexpression led to increased migration and invasion rates of GBC. Rescue experiments (co-transfection) showed that miR-421 overexpression led to attenuated effects of GATA6-AS overexpression.ConclusionGATA6-AS may inhibit cancer cell migration and invasion in GBC by downregulating miR-421.

LncRNA IUR downregulates ZEB1 by upregulating miR-200 to inhibit prostate carcinoma

We in this study investigated the role of imatinib-upregulated lncRNA (IUR) in prostate carcinoma (PC). We observed that IUR was downregulated in PC, and its expression levels decreased with the increase of clinical stages. In PC tissues, microRNA (miR)-200 was positively, while ZEB1 was inversely correlated with IUR. In PC cells, IUR and miR-200 overexpression mediated the downregulated ZEB1. IUR overexpression mediated the upregulation of miR-200, while IUR expression was not significantly affected by miR-200 overexpression. Cell invasion and migration analysis showed that IUR and miR-200 overexpression resulted in decreased invasion and migration rates. ZEB1 overexpression played an opposite role and attenuated the effects of IUR and miR-200 overexpression. Therefore, IUR can downregulate ZEB1 by upregulating miR-200 to inhibit PC cell invasion and migration.

LncRNA NRON down-regulates lncRNA snaR and inhibits cancer cell proliferation in TNBC.

NRON mediates the degradation of tat protein to participate in HIV-1 infection. Interestingly, our study observed the down-regulation of NRON in triple-negative breast cancer (TNBC) tissues compared with paired adjacent healthy tissues. In contrast, lncRNA snaR was up-regulated in TNBC tissues and was inversely correlated with NRON. Expression levels of snaR increased, while expression levels of NRON decreased along with the increase of clinical stages. The snaR overexpression resulted in promoted cancer cell proliferation but did not significantly affect NRON expression. NRON overexpression inhibited cancer cell proliferation and down-regulated snaR. The snaR overexpression reduced the effects of NRON overexpression. We therefore conclude that NRON may down-regulate lncRNA snaR to inhibit cancer cell proliferation in TNBC.

Correlation between the methylation of LIVIN gene and the pathogenesis of bone tumor.

We investigated the correlation between the methylation of LIVIN gene and the pathogenesis of bone tumor at the molecular level, in order to improve the treatment method and enhance the cure rate of bone tumor. The expression level of Livin protein was detected using Western blot analysis, and its expressions in control group and patients were detected by immunohistochemistry. The methylation frequency of LIVIN gene was calculated by direct sequencing. Finally, the prognosis of treatment was investigated by follow-up. The experiment found that Livin protein was not expressed in normal cells, while its expression rate was about 71.4% in 112 patients. The methylation frequency of LIVIN gene was gradually decreased with the increase of clinical stage, and had no significant relationship with age and sex. The prognosis experiment indicated that the lower the methylation frequency of LIVIN gene was, the shorter the survival time would be. The methylation of LIVIN gene was closely related to the pathogenesis of bone tumor, which may be one of the important factors to induce the formation of a bone tumor. In addition, the methylation frequency of LIVIN gene could be used as a biomarker for the prognosis of bone tumor treatment.

Predictive ability of the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification system following infrapopliteal endovascular interventions for critical limb ischemia

The Society for Vascular Surgery (SVS) Lower Extremity Guidelines Committee has composed a new threatened lower extremity classification system that reflects the three major factors that impact amputation risk and clinical management: Wound, Ischemia, and foot Infection (WIfI). Our goal was to evaluate the predictive ability of this scale following any infrapopliteal endovascular intervention for critical limb ischemia (CLI). From 2004 to 2014, a single institution, retrospective chart review was performed at the Beth Israel Deaconess Medical Center for all patients undergoing an infrapopliteal angioplasty for CLI. Throughout these years, 673 limbs underwent an infrapopliteal endovascular intervention for tissue loss (77%), rest pain (13%), stenosis of a previously treated vessel (5%), acute limb ischemia (3%), or claudication (2%). Limbs missing a grade in any WIfI component were excluded. Limbs were stratified into clinical stages 1 to 4 based on the SVS WIfI classification for 1-year amputation risk, as well as a novel WIfI composite score from 0 to 9. Outcomes included patient functional capacity, living status, wound healing, major amputation, major adverse limb events, reintervention, major amputation, or stenosis (RAS) events (>×3.5 step-up by duplex), amputation-free survival, and mortality. Predictors were identified using Kaplan-Meier survival estimates and Cox regression models. Of the 596 limbs with CLI, 551 were classified in all three WIfI domains on a scale of 0 (least severe) to 3 (most severe). Of these 551, 84% were treated for tissue loss and 16% for rest pain. A Cox regression model illustrated thatanincrease in clinical stage increases the rate of major amputation (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.1-2.3). Separate regression models showed that a one-unit increase in the WIfI composite score is associated with a decrease in wound healing (HR, 1.2; 95% CI, 1.1-1.4) and an increase in the rate of RAS events (HR, 1.2; 95% CI, 1.1-1.4) and major amputations (HR, 1.4; 95% CI, 1.2-1.8). This study supports the ability of the SVS WIfI classification system to predict 1-year amputation, RAS events, and wound healing in patients with CLI undergoing endovascular infrapopliteal revascularization procedures.

Cadmium exposure and the risk of breast cancer in Chaoshan population of southeast China.

Recently, there is increasing evidence indicating a link between cadmium exposure and human breast cancer. This study was aimed to explore the relationship between blood cadmium burden and the risk of breast cancer in Chaoshan women with no occupational exposure. Blood cadmium levels (BCLs) were determined in whole blood of 186 breast cancer cases and 139 controls. Basic clinical data and information of age, occupation, blood types, family cancer history, and disease history, as well as other demographic characteristics were collected from medical records. BCLs were detected by graphite-furnace atomizer absorption spectrophotometer (GFAAS). BCLs and proportions of BCLs over 3 μg/L between cases and controls were compared. The relationships between BCLs and breast cancer were explored by comparing BCL differences between/among different characteristics of investigated factors. In addition, BCLs within cases were also compared in relation to the disease clinical stages, tumor-node-metastasis (TNM) stages, and estrogen receptor (ER), progesterone receptor (PR), and Cerb-B2 expressions. The breast cancer patients had a higher median concentration of blood cadmium (2.28, interquartile range 1.57-3.15 μg/L) than the controls (1.77, 1.34-2.57 μg/L; P = 0.001). The proportion of BCLs over 3 μg/L was 2.35 times higher in the breast cancer cases than that of the controls after adjusting for age. Cadmium tends to accumulate in the human body with age and body mass index (BMI) but not associates with type of job, family history, disease history, and other investigated characters. With the increase of clinical stages and T and M stages, the BCLs in the breast cancer cases also increased. BCLs were positively associated with Cerb-B2 expression (r = 0.152, P = 0.038) but not significantly associated with ER and PR expressions. The data obtained show that cadmium concentration is significantly higher in blood of breast cancer patients in comparison to healthy controls. Cadmium seems to be a risk factor of breast cancer, and high cadmium exposure was observed in advanced stages of this disease, which indicates that it may promote the development of breast cancer.