Association of the polymorphisms of the tandem repeat sequence in the thymidylate synthase gene with tumor stage in colon cancer.

e14688 Background: Thymidylate synthase (TS) plays an important role in colorectal carcinogenesis and response to 5FU-based chemotherapy. TS expression can be modified due to polymorphisms in the 5'-untranslated region (5’-UTR) of the gene. The aim of this study is to investigate the association between TS polymorphisms with clinicopathological characteristics of colon carcinomas. Methods: we retrospectively studied 89 individuals with high risk stage II (obstruction, T4 stage, presence of lymphovascular invasion or preoperative CEA > 5.0) and stage III patients submitted to curative intent surgery. DNA was extracted from paraffin embedded tumor tissues and sequenced. The polymorphism studied was the variation of the number of the repeated 28-bp sequences (3 or 2 repeats) of the TS gene 5’-UTR. Results: The frequency of the polymorphisms was: 2R2R in 26 cases (29.2%), 2R3R in 36 cases (40.4%), and 3R3R in 27 cases (30.3%). We did not find associations between the frequencies of these polymorphisms and age, gender, presence of lymphovascular invasion, or level of preoperative CEA. We find a significantly higher proportion of T4 tumors between the 3R3R genotype compared with the 2R2R and 2R3R genotypes (OR=2.69; 95% CI: 1.05 – 6.94; p=0.04). By the other hand, a significantly lower proportion of positive lymph nodes were found among patients with tumors presenting the 3R3R genotype, by comparing with the 2R2R and 2R3R subgroup (OR: 0.28; 95%CI: 0.10 – 0.72; p=0.01). Five-year disease free survival and overall survival were, respectively, 81% and 85% among patients with tumors presenting the 3R3R genotype, and 62% and 67% among patients with tumors presenting 2R2R or 2R3R genotypes. These differences were not statistically significant. Conclusions: in this sample, the TS polymorphic tumor genotype 3R3R was associated with lower risk of lymph node metastases in colon carcinomas.

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Expression and clinical significance of CMTM1 in hepatocellular carcinoma

Open Medicine ◽

10.1515/med-2021-0221 ◽

2021 ◽

Vol 16 (1) ◽

pp. 217-223

Author(s):

Xin Song ◽

Shidong Zhang ◽

Run Tian ◽

Chuanjun Zheng ◽

Yuge Xu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transmembrane Domain ◽

Disease Free Survival ◽

Clinicopathological Characteristics ◽

The Cancer Genome Atlas ◽

High Expression ◽

Chi Square ◽

Tumor Tissues ◽

The Relationship ◽

Low Expression

Abstract Background CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. Methods The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan–Meier model. Results Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients (P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group (P < 0.05). Conclusion CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.

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NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20180907 ◽

2018 ◽

Vol 38 (6) ◽

Cited By ~ 1

Author(s):

Ji-sheng Jing ◽

Hongbo Li ◽

Shun-cai Wang ◽

Jiu-ming Ma ◽

La-qing Yu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Survival Curve ◽

Disease Free Survival ◽

Prognostic Indicator ◽

Clinicopathological Characteristics ◽

Pcr Analysis ◽

Kaplan Meier ◽

Tumor Tissues ◽

The Relationship

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.

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Negative Correlation Between Circular RNA SMARC5 and MicroRNA 432, and Their Clinical Implications in Bladder Cancer Patients

Technology in Cancer Research & Treatment ◽

10.1177/15330338211039110 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110391

Author(s):

Zhijia Zhang ◽

Yanxia Sang ◽

Zhengan Liu ◽

Jinkai Shao

Keyword(s):

Bladder Cancer ◽

Cancer Patients ◽

Survival Data ◽

Tumor Size ◽

Quantitative Polymerase Chain Reaction ◽

Disease Free Survival ◽

Tumor Stage ◽

Circular Rna ◽

High Expression ◽

Tumor Tissues

Objective: Our study aimed to evaluate the correlation of circular RNA SMARCA5 (circ-SMARCA5) and microRNA 432 (miR-432) with clinical characteristics and survival in bladder cancer patients. Methods: Preoperative clinicopathologic features and survival data of 156 bladder cancer patients were retrospectively reviewed. A total of 156 cases of tumor tissues, whereas 71 cases out of 156 available adjacent tissues were obtained from the Pathology Department for circ-SMARCA5 and miR-432 detections using real-time quantitative polymerase chain reaction. Results: Circ-SMARCA5 was upregulated but miR-432 was downregulated in tumor tissues compared with adjacent tissues; meanwhile, circ-SMARCA5 expression was negatively correlated with miR-432 in bladder cancer tissues. Circ-SMARCA5 high expression was correlated with larger tumor size, higher tumor stage, and lymph node (LYN) metastasis. However, miR-432 high expression was correlated with single multiplicity, smaller tumor size, lower tumor stage, less LYN metastasis in bladder cancer patients. Regarding survival, circ-SMARCA5 high expression was correlated with shorter disease-free survival (DFS) and overall survival (OS); whereas, miR-432 high expression was correlated with longer DFS and OS in bladder cancer patients. Further multivariate Cox's regression analysis displayed that circ-SMARCA5 high expression was an independent predictive factor for both worse DFS and OS in bladder cancer patients. Conclusion: Circ-SMARCA5 high expression but miR-432 low expression is correlated with advanced tumor features and poor survival of bladder cancer patients, which present as potential prognostic markers in bladder cancer.

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Overexpression of BUB1B, CCNA2, CDC20, and CDK1 in tumor tissues predicts poor survival in pancreatic ductal adenocarcinoma

Bioscience Reports ◽

10.1042/bsr20182306 ◽

2019 ◽

Vol 39 (2) ◽

Cited By ~ 11

Author(s):

Shu Dong ◽

Fei Huang ◽

Hao Zhang ◽

Qiwen Chen

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Tumor Development ◽

Disease Free Survival ◽

Tumor Stage ◽

Gene Expression Omnibus ◽

Ductal Adenocarcinoma ◽

Advanced Tumor Stage ◽

Kaplan Meier ◽

Advanced Tumor ◽

Tumor Tissues

AbstractOverexpressed genes in tumors usually contributed to aggressiveness in pancreatic ductal adenocarcinoma (PDAC). Using Gene Expression Omnibus (GEO) profiles including GSE46234, GSE71989, and GSE107610, we detected overexpressed genes in tumors with R program, which were enriched by Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO), and Reactome pathway databases. Then, we performed a survival analysis of enriched genes based on TCGA profile. Our results revealed that high BUB1B, CCNA2, CDC20, and CDK1 expression in tumors was significantly associated with worse overall survival (OS) (Log rank P=0.00338, P=0.0447, P=0.00965, and P=0.00479, respectively), which was validated using a Kaplan–Meier plotter with a median cutoff (Log rank P=0.028, P=0.0035, P=0.039, and P=0.0033, respectively). Moreover, overexpression of BUB1B, CCNA2, CDC20, and CDK1 in tumor tissues was significantly associated with disease-free survival (DFS) in PDAC patients (Log rank P=0.00565, P=0.0357, P=0.00104, and P=0.00121, respectively). BUB1B, CCNA2, CDC20, and CDK1 were significantly overexpressed in deceased PDAC patients (all P<0.01) and in patients with recurrence/disease progression (all P<0.05). In addition, PDAC patients with neoplasms of histologic grade G3-4 had significantly higher BUB1B, CCNA2 and CDC20 levels (all P<0.05). In conclusion, the up-regulation of BUB1B, CCNA2, CDC20, CDK1, and WEE1 in tumor tissues are associated with worse OS and DFS in PDAC and is correlated with advanced tumor stage and tumor development.

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Enhancing the Landscape of Colorectal Cancer Using Targeted Deep Sequencing

10.20944/preprints202009.0483.v1 ◽

2020 ◽

Author(s):

Chul Seung Lee ◽

In Hye Song ◽

Ahwon Lee ◽

Jun Kang ◽

Yoon Suk Lee ◽

...

Keyword(s):

Colorectal Cancer ◽

Poor Prognosis ◽

Cox Regression ◽

Disease Free Survival ◽

Tumor Stage ◽

Underlying Disease ◽

Clinicopathological Characteristics ◽

Oncologic Outcomes ◽

Cox Regression Analysis ◽

Targeted Next Generation Sequencing

Targeted next-generation sequencing (NGS) technology detects specific mutations that can provide treatment opportunities for colorectal cancer (CRC) patients. We included 145 CRC patients who underwent surgery. We analyzed the mutation frequencies of common actionable genes and their association with clinicopathological characteristics and oncologic outcomes using targeted NGS. Approximately 97.9% (142) of patients showed somatic mutations. Frequent mutations were observed in TP53 (70%), KRAS (49%), and APC (47%). TP53 mutations were significantly linked to higher overall stage (p=0.038) and lower disease-free survival (DFS) (p=0.039). ATM mutation was significantly associated with higher tumor stage (p=0.012) and shorter overall survival (OS) (p=0.041). Stage 3 and 4 patients with ATM mutations (p=0.023) had shorter OS, and FBXW7 mutation was significantly associated with shorter DFS (p=0.002). In multivariate Cox regression analysis, ATM mutation was an independent biomarker for poor prognosis of OS (p=0.022). TP53 and FBXW7 mutations are independent biomarkers for poor prognosis of DFS (p=0.042 and 0.030, respectively). A comprehensive analysis of the molecular markers for CRC can provide insights into the mechanisms underlying disease progression and help optimize a personalized therapy.

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The expression of versican and its role in pancreatic neuroendocrine tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.254 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 254-254

Author(s):

Zhao Sun ◽

Heli Gao ◽

Junjie Gu ◽

Yuejuan Cheng ◽

Yuanjia Chen ◽

...

Keyword(s):

Tumor Size ◽

Cox Regression ◽

Disease Free Survival ◽

Pancreatic Neuroendocrine Tumor ◽

Tumor Stage ◽

Clinicopathological Characteristics ◽

Specific Expression ◽

Free Survival ◽

The Relationship ◽

Disease Free

254 Background: Pancreatic neuroendocrine tumor (pNET) is a group of rare and heterogeneous tumor. Prognostic biomarkers are essential to better predict patients’ prognosis and approve individualized chemotherapy. According to references, Versican(VCAN) expression plays an important role in the development of various tumors.Our previous study found VCAN had a tumor-specific expression in pNET tissues. Therefore, further study is performed to investigate the relationship between VCAN expression in pNET tissues and patients’ prognosis. Methods: Clinicopathological data of pNET patients who underwent surgery between 2005 and 2010 were collected, followed up and evaluated. VCAN expression was assessed by immunohistochemical (IHC) staining. The relationship between VCAN expression and clinicopathological characteristics of patients were analyzed by Chi square. The expression between VCAN expression and disease-free survival (DFS) of patients were analyzed by Kaplan-Meier. The relationship between patients’ DFS and relative clinicopathological characters were analyzed by Cox regression. Results: 174 pNET patients were enrolled in our research. Among them, 124 patients were VCAN positive and 50 were VCAN negative. VCAN expression was significantly associated with tumor stage. Better disease-free survival (DFS) was observed in patients with VCAN positive compared to those with VCAN negative (124.1±75.71m,99.35±12.14,respectively, p = 0.003).Multivariate analysis demonstrated that VCAN expression, Grade, tumor size were independent prognostic predictor for patients’ prognosis(p = 0.01,0.000,0.001,respectively). Subgroup analysis revealed that VCAN positive predicted a better DFS in patients with Grade 2, Tumor size > 2cm, and Non-functional tumor(p = 0.04,0.002,0.01,respectively). Conclusions: pNET patients with VCAN positive had a longer DFS.

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Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma following previous curative intent surgical resection.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.349 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 349-349

Author(s):

Gaya Spolverato ◽

Yuhree Kim ◽

Sorin Alexandrescu ◽

Hugo Marques ◽

Luca Aldrighetti ◽

...

Keyword(s):

Median Survival ◽

Intrahepatic Cholangiocarcinoma ◽

Systemic Chemotherapy ◽

Disease Free Survival ◽

Best Supportive Care ◽

Clinicopathological Characteristics ◽

Nodal Metastasis ◽

Curative Intent ◽

Initial Surgery ◽

Repeat Hepatic Resection

349 Background: Many patients develop recurrence following resection of intrahepatic cholangiocarcinoma(ICC). Management and outcomes of patients with recurrent ICC following previous curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. Methods: Between 1990-2013, 542 patients who underwent surgery for ICC were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence and recurrence-related management were recorded and analyzed. Results: At initial surgery, treatment was resection only(96.1%) or resection+RFA(3.9%). Overall 5-year survival was 25.9%; 376(69.4%) patients recurred with a median disease-free survival of 11.0 months. Vascular invasion(hazard ratio [HR]=1.43), nodal metastasis(HR=1.40) and poor differentiation(HR=1.30) were predictive of recurrence(all P<0.05). First recurrence site was intrahepatic only (62.0%), extrahepatic only (14.1%), or intra- and extrahepatic(23.9%). Overall 259(68.9%) patients received treatment for recurrent ICC, while 117(31.1%) received best supportive care(BSC). Among patients who received treatment for recurrent disease, therapy consisted of systemic chemotherapy only(49.4%), repeat liver-directed therapy (25.9%), or systemic chemotherapy+liver-directed therapy(24.7%). Repeat liver-directed therapy consisted of repeat hepatic resection±ablation(30.5%), ablation alone (21.4%), and intra-arterial therapy(IAT)(48.1%). Among patients who recurred, median survival from the time of the recurrence was 11.0 months(BSC-7.7 months, systemic chemotherapy only-10.0 months, liver-directed therapy-18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 7.6 months for patients who had IAT(P<0.001). Conclusions: Recurrence following resection of ICC is common, occurring in up to two-thirds of patients. When recurrence occurs, prognosis is poor. In well-selected patients with liver only recurrence, resection+chemotherapy may offer a modest survival benefit.

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Oncogenic Roles of RAD51AP1 in Tumor Tissues Related to Overall Survival and Disease-Free Survival in Hepatocellular Carcinoma

Cancer Control ◽

10.1177/1073274820977149 ◽

2020 ◽

Vol 27 (1) ◽

pp. 107327482097714

Author(s):

Liping Zhuang ◽

Yuan Zhang ◽

Zhiqiang Meng ◽

Zongguo Yang

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Liver Fibrosis ◽

Vascular Invasion ◽

Disease Free Survival ◽

Tumor Stage ◽

Intrahepatic Metastasis ◽

Free Survival ◽

Tumor Tissues ◽

Disease Free

Objective: This study aimed to investigate the associations between RAD51AP1 and the outcomes of hepatocellular carcinoma (HCC). Methods: RAD51AP1 expression levels were compared in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. The Liver Hepatocellular Carcinoma (TCGA, Provisional) and GSE36376 datasets were used for survival analysis. RAD51AP1 associations with clinicopathological features were determined with the GSE36376 dataset. Results: RAD51AP1 mRNA expression was significantly upregulated in advanced liver fibrosis samples (S3-4 vs. S0-2 and G3-4 vs. G0-2) from hepatitis B virus (HBV)-related liver fibrosis patients and in tumor tissues and peripheral blood mononuclear cells (PBMCs) from HCC patients (all P < 0.05). HCC patients with high RAD51AP1 expression had significantly worse overall survival (OS) and disease-free survival (DFS) than those with low RAD51AP1 expression ( P = 0.0034 and P = 0.0012, respectively) in the TCGA dataset, and these findings were validated with the GSE36376 dataset ( P = 0.0074 and P = 0.0003, respectively). A Cox regression model indicated that RAD51AP1 was a risk factor for OS and DFS in HCC patients in GSE36376 (HR = 1.54, 95% CI = 1.02-2.32, P = 0.04 and HR = 1.71, 95% CI = 1.22-2.39, P = 0.002, respectively). Moreover, RAD51AP1 mRNA expression increased gradually with increasing tumor stage, including stratification by American Joint Committee on Cancer (AJCC) stages, Barcelona Clinic Liver Cancer (BCLC) stages and Edmondson grades. In addition, RAD51AP1 was overexpressed in HCC patients with intrahepatic metastasis, major portal vein invasion, vascular invasion and/or an alpha-fetoprotein (AFP) level > 300 ng/ml. Conclusions: Contributing to an advanced tumor stage, intrahepatic metastasis, vascular invasion and AFP level elevation, RAD51AP1 upregulation was significantly associated with OS and DFS in HCC patients.

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MicroRNA Biogenesis Pathway Genes Are Deregulated in Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20184460 ◽

2019 ◽

Vol 20 (18) ◽

pp. 4460 ◽

Cited By ~ 3

Author(s):

Petra Vychytilova-Faltejskova ◽

Alena Svobodova Kovarikova ◽

Tomas Grolich ◽

Vladimir Prochazka ◽

Katerina Slaba ◽

...

Keyword(s):

Colorectal Cancer ◽

Liver Metastases ◽

Disease Free Survival ◽

Tumor Stage ◽

Mirna Biogenesis ◽

Control Mechanisms ◽

Regulate Gene Expression ◽

Free Survival ◽

Over Expression ◽

Tumor Tissues

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Each step of their production and maturation has to be strictly regulated, as any disruption of control mechanisms may lead to cancer. Thus, we have measured the expression of 19 genes involved in miRNAs biogenesis pathway in tumor tissues of 239 colorectal cancer (CRC) patients, 17 CRC patients with liver metastases and 239 adjacent tissues using real-time PCR. Subsequently, the expression of analyzed genes was correlated with the clinical-pathological features as well as with the survival of patients. In total, significant over-expression of all analyzed genes was observed in tumor tissues as well as in liver metastases except for LIN28A/B. Furthermore, it was shown that the deregulated levels of some of the analyzed genes significantly correlate with tumor stage, grade, location, size and lymph node positivity. Finally, high levels of DROSHA and TARBP2 were associated with shorter disease-free survival, while the over-expression of XPO5, TNRC6A and DDX17 was detected in tissues of patients with shorter overall survival and poor prognosis. Our data indicate that changed levels of miRNA biogenesis genes may contribute to origin as well as progression of CRC; thus, these molecules could serve as potential therapeutic targets.

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Role of Autophagy in the Prognosis of Combined Hepatocellular Carcinoma and Cholangiocarcinoma after Surgical Resection

10.21203/rs.3.rs-153575/v1 ◽

2021 ◽

Author(s):

Daw-Shyong Perng ◽

Hung-Yu Lin ◽

Paul Morgan ◽

Tsung-Chin Wu ◽

Chao-Ming Hung ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Disease Free Survival ◽

Clinicopathological Characteristics ◽

Clinical Prognosis ◽

Free Survival ◽

Cox Regression Analysis ◽

Tumor Tissues ◽

Related Proteins

Abstract Background: Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). Methods: We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. Results: We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7% and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68–26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01–0.34), p = 0.004, and 0.07 (0.01–0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85–922), p = 0.008, and 17.9 (1.05–306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2% and 74.6% in high LC3 expression patients and 0% and 0% in those with low LC3 expression. Conclusion: High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.

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