scholarly journals PGM5 is a promising biomarker and may predict the prognosis of colorectal cancer patients

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yifan Sun ◽  
Haihua Long ◽  
Lin Sun ◽  
Xiujuan Sun ◽  
Liping Pang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Migration And Invasion ◽  
Rank Test ◽  
Poor Overall Survival ◽  
Tissue Samples ◽  
Invasion And Migration ◽  
Kaplan Meier ◽  
And Migration

Abstract Background Phosphoglucomutase (PGM), a key enzyme in the metabolism of glucose-1-phosphate and glucose-6-phosphate, has been found to be associated with proliferation, invasion, and metastasis of cancer. However, the expression and function of PGM5 in colorectal cancer (CRC) remains unknown. Methods We tested PGM5 mRNA and protein expression levels in 79 CRC tissue and their matched adjacent tissue samples by qRT-PCR and immunohistochemistry, respectively. Overall survival (OS) was estimated with the Kaplan–Meier method and compared between groups with the log-rank test. We performed multivariable Cox regression analyses to identify factors associated with CRC risk. The cell proliferation, migration and invasion abilities of CRC cells were detected by using CCK-8, Transwell migration and invasion assays, respectively. Results The PGM5 protein levels expression in CRC tissues were significantly lower than those in the adjacent tissues (t = 5.035, P < 0.001), and Kaplan–Meier analysis indicated that low PGM5 expression were significantly associated with poor overall survival (P = 0.0069). Univariate and multivariate analyses demonstrated that PGM5 was an independent risk factor for overall survival (hazard ratio = 0.3951, P = 0.014). PGM5 overexpression significantly inhibited the proliferation, invasion and migration abilities of CRC cells. On the contrary, knockdown of PGM5 promotes the invasion and migration of CRC cells. Conclusions PMG5 regulates proliferation, invasion, and migration in the CRC and decreased PGM5 is associated with poor prognosis. Therefore, PGM5 is a promising biomarker in CRC and decreased PGM5 may predict poor overall survival in patients with CRC.

scholarly journals Development and Validation of a Unique Gignature of Cancer Stemness-related Genes for Predicting the Overall survival of Colorectal Cancer Patients

2020 ◽  
Author(s):  
Ran Wei ◽  
Jichuan Quan ◽  
Shuofeng Li ◽  
Zhao Lu ◽  
Xu Guan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Cancer Stemness ◽  
Poor Overall Survival ◽  
Tissue Samples ◽  
Cox Regression Analysis ◽  
Rna Methylation ◽  
M6a Rna Methylation

Abstract Background: Cancer stem cells (CSCs), which are characterized by self-renewal and plasticity, are highly correlated with tumor metastasis and drug resistance. To fully understand the role of CSCs in colorectal cancer (CRC), we evaluated the stemness traits and prognostic value of stemness-related genes in CRC.Methods: In this study, the data from 616 CRC patients from The Cancer Genome Atlas (TCGA) were assessed and subtyped based on the mRNA expression-based stemness index (mRNAsi). The correlations of cancer stemness with the immune microenvironment, tumor mutational burden (TMB) and N6-methyladenosine (m6A) RNA methylation regulators were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify the crucial stemness-related genes and modules. Furthermore, a prognostic expression signature was constructed using Lasso-penalized Cox regression analysis. The signature was validated via multiplex immunofluorescence staining of tissue samples in an independent cohort of 48 CRC patients.Results: This study suggests that high mRNAsi scores are associated with poor overall survival in stage Ⅳ CRC patients. Moreover, the levels of TMB and m6A RNA methylation regulators were positively correlated with mRNAsi scores, and low mRNAsi scores were characterized by increased immune activity in CRC. The analysis identified 2 key modules and 34 key genes as prognosis-related candidate biomarkers. Finally, a 3-gene prognostic signature (PARPBP, KNSTRN and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort. Conclusions: There is a unique correlation between CSCs and the prognosis of CRC patients, and the novel biomarkers related to cell stemness could accurately predict the clinical outcomes of these patients.

scholarly journals The Prognostic and Predictive Value of SOX2+ Cell Densities in Patients Treated for Colorectal Cancer

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1110
Author(s):  
Tim J. Miller ◽  
Melanie J. McCoy ◽  
Tracey F. Lee-Pullen ◽  
Chidozie C. Anyaegbu ◽  
Christine Hemmings ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Predictive Marker ◽  
Chemotherapy Response ◽  
Poor Overall Survival ◽  
Historical Cohort ◽  
Kaplan Meier ◽  
Response To Chemotherapy ◽  
Cell Densities

SOX2 (sex-determining region-Y homeobox-2) is a transcription factor essential for the maintenance of pluripotency and is also associated with stem-cell-like properties in preclinical cancer models. Our previous study on a cohort of stage III colon cancer patients demonstrated high SOX2+ cell densities were associated with poor prognosis. However, most patients were treated with adjuvant chemotherapy so the prognostic value of SOX2 could not be assessed independently from its value as a predictive marker for non-response to chemotherapy. This study aimed to assess whether SOX2 was a true prognostic marker or a marker for chemotherapy response in a historical cohort of patients, a high proportion of whom were chemotherapy-naïve. SOX2 immunostaining was performed on tissue micro-arrays containing tumor cores from 797 patients with stage II and III colorectal cancer. SOX2+ cell densities were then quantified with StrataQuest digital image analysis software. Overall survival was assessed using Kaplan–Meier estimates and Cox regression. It was found that high SOX2+ cell densities were not associated with poor overall survival. Furthermore, all patients had a significant improvement in survival after 5-fluorouracil (5-FU) treatment, irrespective of their SOX2+ cell density. Therefore, SOX2+ cell densities were not associated with prognosis or chemotherapy benefit in this study. This is in contrast to our previous study, in which most patients received oxaliplatin as part of their treatment, in addition to 5-FU. This suggests SOX2 may predict response to oxaliplatin treatment, but not 5-FU.

scholarly journals Phospholipid Phosphatase 4 as a Driver of Malignant Glioma and Pancreatic Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenxiu Tian ◽  
Ping Wang ◽  
Zhimei Wang ◽  
Huimin Qi ◽  
Junhong Dong ◽  
...  
Keyword(s):  
Overall Survival ◽  
Molecular Mechanisms ◽  
Prognostic Biomarker ◽  
Clinicopathological Features ◽  
Poor Overall Survival ◽  
Tissue Samples ◽  
Invasion And Migration ◽  
Degree Of Malignancy ◽  
And Migration ◽  
High Degree

Glioma and pancreatic cancer are tumors with a high degree of malignancy, morbidity, and mortality. The present study explored possible molecular mechanisms and potential diagnostic and prognostic biomarker-PLPP4 of glioma and PAAD. PLPP4 is differentially elevated in glioma and PAAD tissues. Statistical analysis from TCGA demonstrated that high expression of PLPP4 significantly and positively correlated with clinicopathological features, including pathological grade and poor overall survival in glioma and PAAD patients. Following this, the methylation levels of PLPP4 also affected overall survival in clinical tissue samples. Silencing PLPP4 inhibited proliferation, invasion, and migration in LN229 cells and PANC-1 cells. Moreover, the combination of multiple proteins for the prognosis prediction of glioma and PAAD was evaluated. These results were conducted to elaborate on the potential roles of the biomarker-PLPP4 in clonability and invasion of glioma and PAAD cells.

scholarly journals Biomarker potential of lncRNA GNAS-AS1 in osteosarcoma prognosis and effect on cellular function

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Zhanhu Mi ◽  
Yanyun Dong ◽  
Zhibiao Wang ◽  
Peng Ye
Keyword(s):  
Cell Proliferation ◽  
Cell Function ◽  
Cox Regression ◽  
Bone Cancer ◽  
Prognostic Indicator ◽  
Migration And Invasion ◽  
Rank Test ◽  
Chi Square ◽  
Invasion And Migration ◽  
Novel Therapeutic Strategies

Abstract Background Osteosarcoma (OS) is a type of bone cancer that occurs in children and adolescents at a rate of 5%. The purpose of this study is to explore the lncRNA GNAS-AS1 expression profile, prognosis significance in OS, and biological effect on OS cell function. Methods One hundred eight pairs of tissues were collected, and OS cell lines were purchased. lncRNA GNAS-AS1 expression in these tissues and cells were analyzed by qRT-PCR. Clinical data were analyzed using chi-square tests, Kaplan-Meier curves (log-rank test), and Cox regression. CCK-8 and transwell assay were conducted to analyze the effect of lncRNA GNAS-AS1 on cell proliferation, invasion, and migration. The downstream miRNA was presumed. Results The expression of lncRNA GNAS-AS1 was significantly increased in OS cells and tissues, and related to Enneking staging and distant metastasis. Patients with high lncRNA GNAS-AS1 expression represented shorter overall survival and was an independent prognostic predictor of OS. LncRNA GNAS-AS1 knockdown inhibited cell proliferation, migration, and invasion by regulated miR-490-3p partly at least. Conclusions LncRNA GNAS-AS1 can be used as a prognostic indicator and its inhibition suppress the development of OS, suggesting its value as novel therapeutic strategies in OS.

Outcomes of Surgical and Nonsurgical Treatment for Colorectal Cancer in Nonagenarian Patients

2021 ◽  
pp. 000313482199506
Author(s):  
Youngbae Jeon ◽  
Kyoung-Won Han ◽  
Won-Suk Lee ◽  
Jeong-Heum Baek
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Surgical Treatment ◽  
Postoperative Complications ◽  
Postoperative Mortality ◽  
Nonsurgical Treatment ◽  
Perioperative Outcomes ◽  
Rank Test ◽  
Kaplan Meier ◽  
Number Of Patients

Purpose This study is aimed to evaluate the clinical outcomes of surgical treatment for nonagenarian patients with colorectal cancer. Methods This retrospective single-center study included patients diagnosed with colorectal cancer at the age of ≥90 years between 2004 and 2018. Patient demographics were compared between the operation and nonoperation groups (NOG). Perioperative outcomes, histopathological outcomes, and postoperative complications were evaluated. Overall survival was analyzed using Kaplan-Meier methods and log-rank test. Results A total of 31 patients were included (16 men and 15 women), and the median age was 91 (range: 90‐96) years. The number of patients who underwent surgery and who received nonoperative management was 20 and 11, respectively. No statistical differences in baseline demographics were observed between both groups. None of these patients were treated with perioperative chemotherapy or radiotherapy. Surgery comprised 18 (90.0%) colectomies and 2 (10.0%) transanal excisions. Short-term (≤30 days) and long-term (31‐90 days) postoperative complications occurred in 7 (35.0%) and 4 (20.0%) patients, respectively. No complications needed reoperation, such as anastomosis leakage or bleeding. No postoperative mortality occurred within 30 days: 90-day postoperative mortality occurred in two patients (10.0%), respectively. The median overall survival of the operation group was 31.6 (95% confidence interval: 26.7‐36.5) and that of NOG was 12.5 months (95% CI: 2.4‐22.6) ( P = 0.012). Conclusion Surgical treatment can be considered in carefully selected nonagenarian patients with colorectal cancer in terms of acceptable postoperative morbidity, with better overall survival than the nonsurgical treatment.

Survival Outcomes for Induction vs Adjuvant Chemotherapy in Squamous Cell Carcinoma of the Maxillary Sinus

2018 ◽  
Vol 160 (4) ◽  
pp. 658-663 ◽  
Author(s):  
Phoebe Kuo ◽  
Sina J. Torabi ◽  
Dennis Kraus ◽  
Benjamin L. Judson
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Maxillary Sinus ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Cox Regression ◽  
Rank Test ◽  
Controlled Clinical Trial ◽  
Log Rank Test ◽  
Kaplan Meier

Objective In advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus. Study Design Secondary database analysis. Setting National Cancer Database (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by log-rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison. Results Twenty-three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log-rank test comparing induction to adjuvant chemotherapy was not significant ( P = .076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.

scholarly journals miR-17-5p promotes the invasion and migration of colorectal cancer by regulating HSPB2

2020 ◽  
Author(s):  
Wei fang Yu ◽  
Jia Wang ◽  
Chao Li ◽  
Mingda Xuan ◽  
Shuangshuang Han ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Lymph Node ◽  
Target Genes ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Normal Tissues ◽  
Node Metastasis ◽  
Rescue Experiment ◽  
And Migration

Abstract Background: MicroRNA (miRNA) can affect tumor progression by regulating cell proliferation, apoptosis and metastasis. After miRNA microarray chip analysis of colorectal cancer (CRC) tissues and adjacent normal tissues, a significant upregulation of miR-17-5p expression was found in CRC tissues. However, the underlying mechanism of miR-17-5p in CRC is still unclear.Methods: The levels of miR-17-5p in 47 paired CRC and adjacent normal tissue samples were determined by quantitative real-time PCR (qRT-PCR). CCK-8, colony formation, flow cytometry and transwell assays were used to explore the biological effects of miR-17-5p on CRC cells. In addition, the transcriptome sequencing and miRNA target prediction software were employed to identify targets of miR-17-5p. Luciferase reporter detection was used to demonstrate the direct binding of target genes by miR-17-5p. The rescue experiment was conducted to investigate the biological function of target genes and regulatory mechanism of miR-17-5p on target genes.Results: The expression of miR-17-5p was significantly higher in CRC tissues than in adjacent normal tissues. In CRC group, the expression of miR-17-5p in cancer tissues with lymph node metastasis was higher compared with those without lymph node metastasis. Overexpression of miR-17-5p inhibited CRC cell apoptosis, as well as promoting proliferation, migration and invasion. We hypothesized that HSPB2 might be a target gene of miR-17-5p and validated for the first time that miR-17-5p binds directly to the 3’-UTR of HSPB2. In the rescue experiment, the tumor suppressive effect of HSPB2 was detected and miR-17-5p could promote cell proliferation, migration and invasion by targeting HSPB2.Conclusion: MiR-17-5p promotes invasion and migration by inhibiting HSPB2 in CRC, thereby implicating its potential as a novel diagnostic biomarker and therapeutic target for CRC.

scholarly journals Clinicopathological and molecular differences in colorectal cancer according to location

2019 ◽  
Vol 34 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Yu-Lun Hsu ◽  
Chun-Chi Lin ◽  
Jeng-Kai Jiang ◽  
Hung-Hsin Lin ◽  
Yuan-Tzu Lan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Rank Test ◽  
Advanced Tumor Stage ◽  
Tumor Seeding ◽  
Cox Regression Analysis ◽  
Advanced Tumor ◽  
Tumor Node Metastasis Stage

Purpose: The incidence, pathogenesis, molecular pathways, and outcomes of colorectal cancer vary depending on the location of the tumor. This study aimed to compare the difference in tumor characteristics and the outcome between right-sided colon cancer and left-sided colorectal cancer (LCRC). Materials and methods: A total of 1503 patients with colorectal cancer who underwent surgery at the Taipei Veterans General Hospital between 2000 and 2010 were enrolled in this study. Right-sided colon cancer was defined as cancers in the cecum, ascending colon, and transverse colon, while LCRC was defined as cancers in the splenic flexure colon, descending colon, sigmoid colon, and rectum. The endpoint was overall survival. The mutations were detected via polymerase chain reaction and MASS array. The prognostic value was determined using the log-rank test and the Cox regression analysis. Results: A total of 407 and 1096 cases were classified as right-sided colon cancer and LCRC, respectively. Compared to patients with LCRC, those with right-sided colon cancer had more mucinous type cancer (7.4% vs. 3.5%), poorly differentiated tumor (11.5% vs. 3.6%), and advanced tumor-node-metastasis stage. The risk for peritoneal tumor seeding was higher in the right-sided colon cancer group (12.8% vs. 5.7%). Overall survival was better in LCRC than in right-sided colon cancer ( P=0.036). Conclusions: In our study, right-sided colon cancer had a more advanced tumor stage, a higher risk of peritoneal metastasis, and a poorer outcome than LCRC. Moreover, right-sided colon cancer had more gene mutations in BRAF, KRAS, SMAD4, TGF-β, PIK3CA, PTEN, AKT1, and high microsatellite instability.

scholarly journals Lymphopenia Is Associated with Gross Target Volumes and Fractions in Hepatocellular Carcinoma Patients Treated with External Beam Radiation Therapy and Also Indicates Worse Overall Survival

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Hai-Ge Zhang ◽  
Ping Yang ◽  
Tao Jiang ◽  
Jian-Ying Zhang ◽  
Xue-Juan Jin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Cox Regression ◽  
External Beam Radiation ◽  
Rank Test ◽  
Beam Radiation ◽  
Kaplan Meier ◽  
Target Volumes ◽  
The Relationship

Purpose. To investigate whether lymphocyte nadir induced by radiation is associated with survival and explore its underlying risk factors in patients with hepatocellular carcinoma (HCC). Methods. Total lymphocyte counts were collected from 184 HCC patients treated by radiotherapy (RT) with complete follow-up. Associations between gross tumor volumes (GTVs) and radiation-associated parameters with lymphocyte nadir were evaluated by Pearson/Spearman correlation analysis and multiple linear regression. Kaplan–Meier analysis, log-rank test, as well as univariate and multivariate Cox regression were performed to assess the relationship between lymphocyte nadir and overall survival (OS). Results. GTVs and fractions were negatively related with lymphocyte nadir (p<0.001 and p=0.001, respectively). Lymphocyte nadir and Barcelona Clinic Liver Cancer (BCLC) stage were independent prognostic factors predicting OS of HCC patients (all p<0.001). Patients in the GTV ≤55.0 cc and fractions ≤16 groups were stratified by lymphocyte nadir, and the group with the higher lymphocyte counts (LCs) showed longer survival than the group with lower LCs (p<0.001 and p=0.006, respectively). Patient distribution significantly differed among the RT fraction groups according to BCLC stage (p<0.001). However, stratification of patients in the same BCLC stage by RT fractionation showed that the stereotactic body RT (SBRT) group achieved the best survival. Furthermore, there were significant differences in lymphocyte nadir among patients in the SBRT group. Conclusions. A lower lymphocyte nadir during RT was associated with worse survival among HCC patients. Smaller GTVs and fractions reduced the risk of lymphopenia.

scholarly journals Annexin A2 Coordinates STAT3 to Regulate the Invasion and Migration of Colorectal Cancer CellsIn Vitro

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Dianhui Xiu ◽  
Lin Liu ◽  
Fengli Qiao ◽  
Haishan Yang ◽  
Lu Cui ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Annexin A2 ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Protein Levels ◽  
And Migration

The present study aimed to reveal the expression of STAT3 and Anxa 2 in CRC specimens and to investigate the effects of STAT3 and Anxa 2 signaling on the proliferation, invasion, and migration in CRC Caco-2 cells. Results demonstrated that both Anxa 2 and STAT3 were highly expressed in CRC specimens in both mRNA and protein levels, with or without phosphorylation (Tyrosine 23 in Anxa 2 and Tyrosine 705 in STAT3). And the upregulated Anxa 2 promoted the phosphorylation of STAT3 (Tyrosine 705) in CRC Caco-2 cells. The upregulated Anxa 2 promoted the proliferation, migration, and invasion of Caco-2 cells in vitro. Moreover, the STAT3 knockdown also repressed the proliferation, migration, and invasion of Caco-2 cells. In conclusion, the overexpressed Annexin A2 regulated the proliferation, invasion, and migration in CRC cells in an association with STAT3.

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