Effect of Baseline Characteristics and Tumor Burden on Vaspin Expression and Progressive Disease in Operable Colorectal Cancer

Colorectal cancer is a highly heterogeneous malignancy in the Asian population, and it is considered an important prognostic factor for baseline characteristics, tumor burden, and tumor markers. This study investigated the effect of baseline characteristics and tumor burden on tumor marker expression and progressive disease in colorectal cancer by using partial least squares variance-based path modeling (PLS-PM). PLS-PM can be used to evaluate the complex relationship between prognostic variables and progressive disease status with a small sample of measurements and structural models. A total of 89 tissue samples of colorectal cancer were analyzed. Our results suggested that the expression of visceral adipose tissue-derived serpin (vaspin) is a potential indicator of colorectal cancer progression and may be affected by baseline characteristics such as age, sex, body mass index, and diabetes mellitus. Moreover, according to the characteristics of tumor burden, the expression of vaspin was generally higher in each progressive disease patient. The overall findings suggest that vaspin is a potential indicator of the progressive disease and may be affected by the baseline characteristics of patients.

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Radiation-Induced Overexpression of TGFβ and PODXL Contributes to Colorectal Cancer Cell Radioresistance through Enhanced Motility

Cells ◽

10.3390/cells10082087 ◽

2021 ◽

Vol 10 (8) ◽

pp. 2087

Author(s):

Hyunjung Lee ◽

Joon-Seog Kong ◽

Seung-Sook Lee ◽

Areumnuri Kim

Keyword(s):

Colorectal Cancer ◽

Cancer Cell ◽

Cancer Progression ◽

Surface Glycoprotein ◽

Tissue Samples ◽

Cell Surface Glycoprotein ◽

Matrix Deposition ◽

Metastatic Relapse ◽

Radiation Induced ◽

And Migration

The primary cause of colorectal cancer (CRC) recurrence is increased distant metastasis after radiotherapy, so there is a need for targeted therapeutic approaches to reduce the metastatic-relapse risk. Dysregulation of the cell-surface glycoprotein podocalyxin-like protein (PODXL) plays an important role in promoting cancer-cell motility and is associated with poor prognoses for many malignancy types. We found that CRC cells exposed to radiation demonstrated increased TGFβ and PODXL expressions, resulting in increased migration and invasiveness due to increased extracellular matrix deposition. In addition, both TGFβ and PODXL were highly expressed in tissue samples from radiotherapy-treated CRC patients compared to those from patients without this treatment. However, it is unclear whether TGFβ and PODXL interactions are involved in cancer-progression resistance after radiation exposure in CRC. Here, using CRC cells, we showed that silencing PODXL blocked radiation-induced cell migration and invasiveness. Cell treatment with galunisertib (a TGFβ-pathway inhibitor) also led to reduced viability and migration, suggesting that its clinical use may enhance the cytotoxic effects of radiation and lead to the effective inhibition of CRC progression. Overall, the results demonstrate that downregulation of TGFβ and its-mediated PODXL may provide potential therapeutic targets for patients with radiotherapy-resistant CRC.

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LINC01224 promotes colorectal cancer progression through targeting miR-485-5p/MYO6 axis

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02389-x ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jingfeng Gu ◽

Liang Dong ◽

Yun Wang ◽

Wenjia Nie ◽

Wencong Liu ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Proliferation ◽

Cancer Progression ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Binding Interaction ◽

Tissue Samples ◽

Rna Immunoprecipitation ◽

Colorectal Cancer Progression ◽

Transcription Factor Yy1

Abstract Background Long noncoding RNAs (lncRNAs) are related to colorectal cancer (CRC) development. However, the role and mechanism of lncRNA LINC01224 in CRC development are largely unknown. Methods LINC01224, Yin Yang 1 (YY1), microRNA (miR)-485-5p, and myosins of class VI (MYO6) levels were examined using quantitative reverse transcription polymerase chain reaction and western blotting. Functional analyses were processed through CCK-8, colony formation, flow cytometry, transwell, and xenograft analyses. Dual-luciferase reporter, chromatin immunoprecipitation (ChIP), RNA immunoprecipitation, and pull-down assays were conducted to analyze the binding interaction. Results LINC01224 abundance was elevated in CRC tissue samples and cell lines. Elevated LINC01224 might indicate the lower 5-year overall survival in 52 CRC patients. LINC01224 was upregulated via the transcription factor YY1. LINC01224 knockdown restrained CRC cell proliferation, migration, and invasion and increased apoptosis. MiR-485-5p was sponged by LINC01224, and miR-485-5p downregulation relieved the influence of LINC01224 interference on CRC progression. MYO6 was targeted via miR-485-5p and regulated via LINC01224/miR-485-5p axis. MiR-485-5p overexpression suppressed CRC cell proliferation, migration, and invasion and facilitated apoptosis. MYO6 upregulation mitigated the role of miR-485-5p. LINC01224 knockdown decreased xenograft tumor growth. Conclusion YY1-induced LINC01224 regulates CRC development via modulating miR-485-5p/MYO6 axis.

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Regulation Network of Colorectal-Cancer-Specific Enhancers in the Progression of Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22158337 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8337

Author(s):

Bohan Chen ◽

Yiping Ma ◽

Jinfang Bi ◽

Wenbin Wang ◽

Anshun He ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Target Genes ◽

Colorectal Cancer Cell Line ◽

Tissue Samples ◽

Colon Cells ◽

Colorectal Cancer Cells ◽

Regulation Network

Enhancers regulate multiple genes via higher-order chromatin structures, and they further affect cancer progression. Epigenetic changes in cancer cells activate several cancer-specific enhancers that are silenced in normal cells. These cancer-specific enhancers are potential therapeutic targets of cancer. However, the functions and regulation networks of colorectal-cancer-specific enhancers are still unknown. In this study, we profile colorectal-cancer-specific enhancers and reveal their regulation network through the analysis of HiChIP data that were derived from a colorectal cancer cell line and Hi-C and RNA-seq data that were derived from tissue samples by in silico analysis and in vitro experiments. Enhancer–promoter loops in colorectal cancer cells containing colorectal-cancer-specific enhancers are involved in more than 50% of the topological associated domains (TADs) changed in colorectal cancer cells compared to normal colon cells. In addition, colorectal-cancer-specific enhancers interact with 152 genes that are significantly and highly expressed in colorectal cancer cells. These colorectal-cancer-specific enhancer target genes include ITGB4, RECQL4, MSLN, and GDF15. We propose that the regulation network of colorectal-cancer-specific enhancers plays an important role in the progression of colorectal cancer.

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Study of FGF14 gene expression and cancer progression in colorectal cancer tissue samples

MEDICAL SCIENCES JOURNAL ◽

10.29252/iau.29.3.210 ◽

2019 ◽

Vol 29 (3) ◽

pp. 210-215

Author(s):

Homayoun Jalali Tafti ◽

Mehrdad Hashemi ◽

Khalil Alimohammadzadeh ◽

◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Cancer Progression ◽

Cancer Tissue ◽

Tissue Samples ◽

Colorectal Cancer Tissue

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Metadherin (MTDH) Overexpression Significantly Correlates with Advanced Tumor Grade and Stages among Colorectal Cancer Patients

10.21203/rs.3.rs-818656/v1 ◽

2021 ◽

Author(s):

Aimen Sultan ◽

Namood-e Sahar ◽

Syeda Kiran Riaz ◽

Javeria Qadir ◽

Shahzad Hussain Waqar ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Tumor Tissue ◽

Tumor Grade ◽

Ki 67 ◽

Core Element ◽

Age And Gender ◽

Tissue Samples ◽

Advanced Tumor ◽

And Gender

Abstract BackgroundColorectal cancer is the 4th leading cause of cancer related deaths affecting both men and women worldwide. In the present study, any probable role of MTDH mRNA expression in CRC tumorigenesis was explored using both discovery and validation cohorts. Methods and resultsAfter prior ethical and biosafety approvals, tumor tissue samples along with their adjacent controls were collected for this study from Pakistani patients diagnosed with colorectal cancer. RNA was isolated using Trizol reagent, followed by cDNA synthesis. Transcript analysis of MTDH was performed by using qPCR. Moreover, genome-wide expression of MTDH was also determined through micro-array data analysis using BRB- Array Tools software. MTDH expression was significantly high in tumor tissue samples (p<0.05) compared to their respective controls. Likewise, results of microarray analysis also revealed overamplification of MTDH in tumor samples as compared to controls. Expression of MTDH was also found to be positively correlated with KI-67 index (p<0.05) and were observed to be significantly upregulated in advance tumor grade (p< 0.05) and stage (p< 0.05). However, no association of MTDH overexpression with age and gender could be established. ConclusionHence, it can be concluded that MTDH is a core element that plays a pivotal role in colorectal tumorigenesis irrespective of patient’s age and gender. Molecular insight into the tumor microenvironment revealed MTDH as a niche, representing distinctive framework for cancer progression, thus, making it an innovative target strategy for colorectal cancer treatment.

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lncRNAs in Non-Malignant Tissue Have Prognostic Value in Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms19092672 ◽

2018 ◽

Vol 19 (9) ◽

pp. 2672 ◽

Cited By ~ 12

Author(s):

Jana-Aletta Thiele ◽

Petr Hosek ◽

Eva Kralovcova ◽

Pavel Ostasov ◽

Vaclav Liska ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Cancer Progression ◽

Proportional Hazards ◽

Disease Free Survival ◽

Cox Proportional Hazards ◽

Wilcoxon Test ◽

Tumour Tissue ◽

Solid Cancer ◽

Tissue Samples

Although colorectal cancer (CRC) is the third most frequent cause of cancer related death in Europe, clinically relevant biomarkers for therapy guidance and prognosis are insufficiently reliable. Long non-coding RNAs (lncRNAs) are RNAs over 200 nucleotides long that are not translated into proteins but can influence biological processes. There is emerging evidence for their involvement in solid cancer as oncogenes, tumour suppressors or regulators of cell proliferation and metastasis development. The goal of this study was to evaluate the prognostic effect of selected lncRNAs in a retrospective study on CRC patients from the Czech Republic. We used a quantitative PCR approach to measure the expression in paired non-malignant and tumour tissue samples of CRC patients of nine lncRNAs previously shown to be involved in cancer progression—ANRIL, CCAT1, GAS5, linc-ROR, MALAT1, MIR155HG, PCAT1, SPRY4-IT1 and TUG1. Associations between expression and expression ratios and clinical characteristics and survival were assessed by using univariable Cox proportional hazards models, Kaplan-Meier estimations with the Gehan-Wilcoxon test, the Mann-Whitney U test, the Kruskal-Wallis test and Spearman’s correlations. A comparison of expression in tumour tissue (TT) and non-malignant mucosa tissue (MT) showed significant upregulation of CCAT1 and linc-ROR in TT (p < 0.001 and p = 0.001, respectively) and downregulation of ANRIL, MIR155HG and MALAT1 (p = 0.001, p = 0.010, p = 0.001, respectively). Linc-ROR was significantly associated with the presence of synchronous metastases (p = 0.033). For individual tissue types, lower MIR155HG expression in TT was correlated with both shorter overall survival (p = 0.008) and shorter disease-free survival (p = 0.040). In MT, expression ratios of CCAT1/ANRIL and CCAT1/MIR155HG were associated with overall survival (p = 0.005 and p = 0.006, respectively). Our results revealed that changes in expression of lncRNAs between MT and TT hold potential to be used as prognostic biomarkers in CRC patients. Moreover, the ratios of CCAT1 to ANRIL and MIR155HG in MT also exhibit potential for prognosis assessment without tumour sampling. Our results also indicate that cancer progression is associated with detrimental system-wide changes in patient tissue, which might govern patient survival even after successful elimination of tumour or cancerous cells.

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Mode of progression after radioembolization in patients with colorectal cancer liver metastases

EJNMMI Research ◽

10.1186/s13550-020-00697-z ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Caren van Roekel ◽

Jennifer M. J. Jongen ◽

Maarten L. J. Smits ◽

Sjoerd G. Elias ◽

Miriam Koopman ◽

...

Keyword(s):

Colorectal Cancer ◽

Progressive Disease ◽

Complete Response ◽

Extrahepatic Disease ◽

Colorectal Cancer Liver Metastases ◽

Dominant Disease ◽

Baseline Characteristics ◽

Extrahepatic Metastases ◽

Colorectal Cancer Patients ◽

The Impact

Abstract Background Radioembolization is an established treatment modality in colorectal cancer patients with liver-dominant disease in a salvage setting. Selection of patients who will benefit most is of vital importance. The aim of this study was to assess response (and mode of progression) at 3 months after radioembolization and the impact of baseline characteristics. Methods Three months after radioembolization with either yttrium-90 resin/glass or holmium-166, anatomic response, according to RECIST 1.1, was evaluated in 90 patients. Correlations between baseline characteristics and efficacy were evaluated. For more detailed analysis of progressive disease as a dismal clinical entity, distinction was made between intra- and extrahepatic progression, and between progression of existing metastases and new metastases. Results Forty-two patients (47%) had extrahepatic disease (up to five ≥ 1 cm lung nodules, and ≤ 2 cm lymph nodes) at baseline. No patients showed complete response, 5 (5.5%) patients had partial response, 16 (17.8%) had stable disease, and 69 (76.7%) had progressive disease. Most progressive patients (67/69; 97%) had new metastases (intra-hepatic N = 11, extrahepatic N = 32; or both N = 24). Significantly fewer patients had progressive disease in the group of patients presenting without extrahepatic metastases at baseline (63% versus 93%; p = 0.0016). Median overall survival in patients with extrahepatic disease was 6.5 months, versus 10 months in patients without extrahepatic disease at baseline (hazard ratio 1.79, 95%CI 1.24–2.57). Conclusions Response at 3-month follow-up and survival were heavily influenced by new metastases. Patients with extrahepatic disease at baseline had a worse outcome compared to patients without.

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ADAMTS4 is upregulated in colorectal cancer and could be a useful prognostic indicator of colorectal cancer

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.66.1.42 ◽

2020 ◽

Vol 66 (1) ◽

pp. 42-47 ◽

Cited By ~ 1

Author(s):

Xue-Qin Shang ◽

Kui-Liang Liu ◽

Qian Li ◽

Yue-Qiong Lao ◽

Nan-Shan Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Lines ◽

Cancer Progression ◽

Clinical Sample ◽

Prognostic Indicator ◽

Clinical Samples ◽

Tissue Samples ◽

Non Invasive ◽

Colorectal Cancer Progression

SUMMARY OBJECTIVE ADAMTS4 is a member of the ADAMTS4 family, which secretes proteinases. The mechanism of tumor metastasis may be correlated to its promotion of angiogenesis. It was determined whether ADAMTS4 participates in colorectal cancer progression. Methods The expression in clinical samples and CRC cell lines was investigated. Using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and RT-PCR, the expression of ADAMTS4 was determined in colorectal tumors of different cancer stages and anatomic sites, and in three cell lines of different aggressiveness. Results The overexpression of ADAMTS4 was observed in tissue samples by IHC, and this was mainly located in the cytoplasm, as detected by FISH. The qRT-PCR and western blot analyses further supported the clinical sample findings. Conclusion The present data support the notion that the overexpression of ADAMTS4 in CRC might be useful as a non-invasive biomarker for detecting CRC in patients.

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Computational Analysis of miRNA and their Gene Targets Significantly Involved in Colorectal Cancer Progression

MicroRNA ◽

10.2174/2211536607666180803100246 ◽

2018 ◽

Vol 8 (1) ◽

pp. 68-75 ◽

Cited By ~ 1

Author(s):

Jeyalakshmi Kandhavelu ◽

Kumar Subramanian ◽

Amber Khan ◽

Aadilah Omar ◽

Paul Ruff ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Progression ◽

Target Prediction ◽

Computational Prediction ◽

Initial Step ◽

Kegg Pathways ◽

Candidate Mirnas ◽

Common Cancer ◽

Colon Cancer Progression

Background:Globally, colorectal cancer (CRC) is the third most common cancer in women and the fourth most common cancer in men. Dysregulation of small non-coding miRNAs have been correlated with colon cancer progression. Since there are increasing reports of candidate miRNAs as potential biomarkers for CRC, this makes it important to explore common miRNA biomarkers for colon cancer. As computational prediction of miRNA targets is a critical initial step in identifying miRNA: mRNA target interactions for validation, we aim here to construct a potential miRNA network and its gene targets for colon cancer from previously reported candidate miRNAs, inclusive of 10 up- and 9 down-regulated miRNAs from tissues; and 10 circulatory miRNAs. </P><P> Methods: The gene targets were predicted using DIANA-microT-CDS and TarBaseV7.0 databases. Each miRNA and its targets were analyzed further for colon cancer hotspot genes, whereupon DAVID analysis and mirPath were used for KEGG pathway analysis.Results:We have predicted 874 and 157 gene targets for tissue and serum specific miRNA candidates, respectively. The enrichment of miRNA revealed that particularly hsa-miR-424-5p, hsa-miR-96-5p, hsa-miR-1290, hsa-miR-224, hsa-miR-133a and has-miR-363-3p present possible targets for colon cancer hallmark genes, including BRAF, KRAS, EGFR, APC, amongst others. DAVID analysis of miRNA and associated gene targets revealed the KEGG pathways most related to cancer and colon cancer. Similar results were observed in mirPath analysis. A new insight gained in the colon cancer network pathway was the association of hsa-mir-133a and hsa-mir-96-5p with the PI3K-AKT signaling pathway. In the present study, target prediction shows that while hsa-mir-424-5p has an association with mostly 10 colon cancer hallmark genes, only their associations with MAP2 and CCND1 have been experimentally validated.These miRNAs and their targets require further evaluation for a better understanding of their associations, ultimately with the potential to develop novel therapeutic targets.

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TEAD4 modulated LncRNA MNX1-AS1 contributes to gastric cancer progression partly through suppressing BTG2 and activating BCL2

Molecular Cancer ◽

10.1186/s12943-019-1104-1 ◽

2020 ◽

Vol 19 (1) ◽

Cited By ~ 12

Author(s):

You Shuai ◽

Zhonghua Ma ◽

Weitao Liu ◽

Tao Yu ◽

Changsheng Yan ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Mechanistic Model ◽

Ectopic Expression ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Tissue Samples ◽

Reporter Assays

Abstract Background Gastric cancer (GC) is the third leading cause of cancer-related mortality globally. Long noncoding RNAs (lncRNAs) are dysregulated in obvious malignancies including GC and exploring the regulatory mechanisms underlying their expression is an attractive research area. However, these molecular mechanisms require further clarification, especially upstream mechanisms. Methods LncRNA MNX1-AS1 expression in GC tissue samples was investigated via microarray analysis and further determined in a cohort of GC tissues via quantitative reverse transcription polymerase chain reaction (qRT-PCR) assays. Cell proliferation and flow cytometry assays were performed to confirm the roles of MNX1-AS1 in GC proliferation, cell cycle regulation, and apoptosis. The influence of MNX1-AS1 on GC cell migration and invasion was explored with Transwell assays. A xenograft tumour model was established to verify the effects of MNX1-AS1 on in vivo tumourigenesis. The TEAD4-involved upstream regulatory mechanism of MNX1-AS1 was explored through ChIP and luciferase reporter assays. The mechanistic model of MNX1-AS1 in regulating gene expression was further detected by subcellular fractionation, FISH, RIP, ChIP and luciferase reporter assays. Results It was found that MNX1-AS1 displayed obvious upregulation in GC tissue samples and cell lines, and ectopic expression of MNX1-AS1 predicted poor clinical outcomes for patients with GC. Overexpressed MNX1-AS1 expression promoted proliferation, migration and invasion of GC cells markedly, whereas decreased MNX1-AS1 expression elicited the opposite effects. Consistent with the in vitro results, MNX1-AS1 depletion effectively inhibited the growth of xenograft tumour in vivo. Mechanistically, TEAD4 directly bound the promoter region of MNX1-AS1 and stimulated the transcription of MNX1-AS1. Furthermore, MNX1-AS1 can sponge miR-6785-5p to upregulate the expression of BCL2 in GC cells. Meanwhile, MNX1-AS1 suppressed the transcription of BTG2 by recruiting polycomb repressive complex 2 to BTG2 promoter regions. Conclusions Our findings demonstrate that MNX1-AS1 may be able to serve as a prognostic indicator in GC patients and that TEAD4-activatd MNX1-AS1 can promote GC progression through EZH2/BTG2 and miR-6785-5p/BCL2 axes, implicating it as a novel and potent target for the treatment of GC.

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