scholarly journals Molecular and phenotypic profiling of colorectal cancer patients in West Africa reveals biological insights

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Olusegun Isaac Alatise ◽  
Gregory C. Knapp ◽  
Avinash Sharma ◽  
Walid K. Chatila ◽  
Olukayode A. Arowolo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
West Africa ◽  
The Cancer Genome Atlas ◽  
Cancer Center ◽  
Rectal Disease ◽  
Ras Pathway ◽  
Phenotypic Profile ◽  
Cancer Genome Atlas ◽  
Colorectal Cancer Patients ◽  
Generation Sequencing

AbstractUnderstanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is vital to addressing the regions rising burden of disease. Tissue from unselected Nigerian patients was analyzed with a multigene, next-generation sequencing assay. The rate of microsatellite instability is significantly higher among Nigerian CRC patients (28.1%) than patients from The Cancer Genome Atlas (TCGA, 14.2%) and Memorial Sloan Kettering Cancer Center (MSKCC, 8.5%, P < 0.001). In microsatellite-stable cases, tumors from Nigerian patients are less likely to have APC mutations (39.1% vs. 76.0% MSKCC P < 0.001) and WNT pathway alterations (47.8% vs. 81.9% MSKCC, P < 0.001); whereas RAS pathway alteration is more prevalent (76.1% vs. 59.6%, P = 0.03). Nigerian CRC patients are also younger and more likely to present with rectal disease (50.8% vs. 33.7% MSKCC, P < 0.001). The findings suggest a unique biology of CRC in Nigeria, which emphasizes the need for regional data to guide diagnostic and treatment approaches for patients in West Africa.

High preoperative levels of circulating SFRP5 predict better prognosis in colorectal cancer patients

2020 ◽  
Vol 16 (31) ◽  
pp. 2499-2509
Author(s):  
Chandra Kirana ◽  
Eric Smith ◽  
Doan T Ngo ◽  
Markus I Trochsler ◽  
Peter J Hewett ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Value ◽  
Disease Free Survival ◽  
Normal Mucosa ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Cancer Genome Atlas ◽  
Colorectal Cancer Patients ◽  
Diagnostic And Prognostic Value

The purpose of this research was to investigate the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC). We evaluated preoperative cSFRP5 levels in CRC patients and controls (n = 208). We found significantly higher cSFRP5 levels in CRC patients compared with non-CRC controls (p < 0.001). Levels of cSFRP5 were significantly lower in CRC patients with either vascular invasion (p = 0.001) or liver metastasis (p = 0.016). High cSFRP5 levels were associated with longer disease-free survival in both univariate (p = 0.024) and multivariate (p = 0.015) analyses. Analysis of an independent tissue cohort from The Cancer Genome Atlas database revealed significantly lower SFRP5 RNA expression in CRC tumor tissue compared with adjacent normal mucosa (n = 590 vs 47; p < 0.0001). Our findings confirm the role of cSFRP5 as a physiologic tumor suppressor and demonstrate its potential diagnostic and prognostic value in CRC.

scholarly journals Exceptional Chemotherapy Response in Metastatic Colorectal Cancer Associated With Hyper-Indel–Hypermutated Cancer Genome and Comutation of POLD1 and MLH1

2017 ◽  
pp. 1-12
Author(s):  
Manish R. Sharma ◽  
James T. Auman ◽  
Nirali M. Patel ◽  
Juneko E. Grilley-Olson ◽  
Xiaobei Zhao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Somatic Mutation ◽  
Mutation Rate ◽  
Germ Line ◽  
Cancer Genome ◽  
The Cancer Genome Atlas ◽  
Response To Chemotherapy ◽  
Cancer Genome Atlas ◽  
Genome Atlas

Purpose A 73-year-old woman with metastatic colon cancer experienced a complete response to chemotherapy with dose-intensified irinotecan that has been durable for 5 years. We sequenced her tumor and germ line DNA and looked for similar patterns in publicly available genomic data from patients with colorectal cancer. Patients and Methods Tumor DNA was obtained from a biopsy before therapy, and germ line DNA was obtained from blood. Tumor and germline DNA were sequenced using a commercial panel with approximately 250 genes. Whole-genome amplification and exome sequencing were performed for POLE and POLD1. A POLD1 mutation was confirmed by Sanger sequencing. The somatic mutation and clinical annotation data files from the colon (n = 461) and rectal (n = 171) adenocarcinoma data sets were downloaded from The Cancer Genome Atlas data portal and analyzed for patterns of mutations and clinical outcomes in patients with POLE- and/or POLD1-mutated tumors. Results The pattern of alterations included APC biallelic inactivation and microsatellite instability high (MSI-H) phenotype, with somatic inactivation of MLH1 and hypermutation (estimated mutation rate > 200 per megabase). The extremely high mutation rate led us to investigate additional mechanisms for hypermutation, including loss of function of POLE. POLE was unaltered, but a related gene not typically associated with somatic mutation in colon cancer, POLD1, had a somatic mutation c.2171G>A [p.Gly724Glu]. Additionally, we noted that the high mutation rate was largely composed of dinucleotide deletions. A similar pattern of hypermutation (dinucleotide deletions, POLD1 mutations, MSI-H) was found in tumors from The Cancer Genome Atlas. Conclusion POLD1 mutation with associated MSI-H and hyper-indel–hypermutated cancer genome characterizes a previously unrecognized variant of colon cancer that was found in this patient with an exceptional response to chemotherapy.

Identification of a lncRNA prognostic signature-related to stem cell index and its significance in colorectal cancer

2021 ◽  
Author(s):  
Xiao-Cheng Wang ◽  
Ya Liu ◽  
Fei-Wu Long ◽  
Liang-Ren Liu ◽  
Chuan-Wen Fan
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Markers ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Free Survival ◽  
Cancer Genome Atlas ◽  
Bioinformatic Approaches ◽  
Cell Phenotypes ◽  
The Relationship

Background: The relationship between long noncoding RNAs (lncRNAs) and the mRNA stemness index (mRNAsi) in colorectal cancer (CRC) is still unclear. Materials & methods: The mRNAsi, mRNAsi-related lncRNAs and their clinical significance were analyzed by bioinformatic approaches in The Cancer Genome Atlas (TCGA)-COREAD dataset. Results: mRNAsi was negatively related to pathological features but positively related to overall survival and recurrence-free survival in CRC. A five mRNAsi-related lncRNAs prognostic signature was further developed and showed independent prognostic factors related to overall survival in CRC patients, due to the five mRNAsi-related lncRNAs involved in several pathways of the cancer stem cells and malignant cancer cell phenotypes. Conclusion: The present study highlights the potential roles of mRNAsi-related lncRNAs as alternative prognostic markers.

scholarly journals Diet and weight management by people with nonmetastatic colorectal cancer during chemotherapy: mixed methods research

2020 ◽  
Vol 9 (2) ◽  
pp. CRC16
Author(s):  
Jane B Hopkinson ◽  
Catherine Kazmi ◽  
Jayne Elias ◽  
Sally Wheelwright ◽  
Rhiannon Williams ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dietary Intake ◽  
Mixed Methods Research ◽  
Nutritional Risk ◽  
Self Management ◽  
Cancer Center ◽  
Colorectal Cancer Patients ◽  
Treatment Tolerance ◽  
Maximum Variation Sample

Aim: To investigate self-management of dietary intake by colorectal cancer patients receiving chemotherapy. Methods: A questionnaire was administered to 92 patients with nonmetastatic colorectal cancer receiving chemotherapy treatment at a UK cancer center in 2018–19. A maximum variation sample of 20 patients who completed the questionnaire were interviewed. Results: More than three in five patients were at nutritional risk but fewer than one in five were concerned about dietary intake or weight. Self-management of diet and weight was inconsistent with achieving the nutritional intake recommended by clinical guidelines on nutrition in cancer. Conclusion: There is potential for psychoeducation to support change in self-management of nutritional risk, with implications for better treatment tolerance and outcomes including quality of life.

Initiation and Discontinuation of Complementary Therapy Among Cancer Patients

2007 ◽  
Vol 25 (33) ◽  
pp. 5267-5274 ◽  
Author(s):  
Sung-Gyeong Kim ◽  
Eun-Cheol Park ◽  
Jae-Hyun Park ◽  
Myung-Il Hahm ◽  
Jin-Hwa Lim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Initial Treatment ◽  
Stage Iv ◽  
Complementary Therapy ◽  
Cancer Center ◽  
Cumulative Probability ◽  
Colorectal Cancer Patients ◽  
The Impact

PurposeTo identify the initiation or discontinuation of complementary therapy (CT) and determine the impact of sociodemographic and clinical factors on CT use among cancer patients.Patients and MethodsEligible patients were age 20 or older; newly diagnosed with stomach, liver, or colorectal cancer; and started their initial treatment at the National Cancer Center, Korea, between April 1, 2001, and April 30, 2003. In total, 541 cancer patients were surveyed in face-to-face interviews at baseline, and telephone follow-up interviews were performed every 3 months for 3 years.ResultsA total of 281 patients commenced CT after diagnosis; 164 patients stopped using CT during the follow-up period. The overall cumulative probability of starting CT at 1, 2, and 3 years was 50%, 54%, and 55%, respectively. In a Cox multivariate analysis, stomach and liver cancer were associated with an increased probability of initiating CT compared with colorectal cancer. Patients who were classified as stage I, II, or III at diagnosis were associated with a decreased probability of discontinuing CT compared with stage IV.ConclusionMost cancer patients started to use CT during the initial treatment period. Thus, physicians should communicate with cancer patients about CT at this phase. In particular, more attention should be paid to women and individuals with higher household incomes because these groups are more likely to start CT.

scholarly journals Downregulated SPINK4 is associated with poor survival in colorectal cancer

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaojie Wang ◽  
Qian Yu ◽  
Waleed M. Ghareeb ◽  
Yiyi Zhang ◽  
Xingrong Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Expression Data ◽  
Poor Survival ◽  
Protein Levels ◽  
Normal Tissues ◽  
Human Protein Atlas ◽  
Cancer Genome Atlas ◽  
Independent Indicator

Abstract Background SPINK4 is known as a gastrointestinal peptide in the gastrointestinal tract and is abundantly expressed in human goblet cells. The clinical significance of SPINK4 in colorectal cancer (CRC) is largely unknown. Methods We retrieved the expression data of 1168 CRC patients from 3 Gene Expression Omnibus (GEO) datasets (GSE24551, GSE39582, GSE32323) and The Cancer Genome Atlas (TCGA) to compare the expression level of SPINK4 between CRC tissues and normal colorectal tissues and to evaluate its value in predicting the survival of CRC patients. At the protein level, these results were further confirmed by data mining in the Human Protein Atlas and by immunohistochemical staining of samples from 81 CRC cases in our own center. Results SPINK4 expression was downregulated in CRC compared with that in normal tissues, and decreased SPINK4 expression at both the mRNA and protein levels was associated with poor prognosis in CRC patients from all 3 GEO datasets, the TCGA database and our cohort. Additionally, lower SPINK4 expression was significantly related to higher TNM stage. Moreover, in multivariate regression, SPINK4 was confirmed as an independent indicator of poor survival in CRC patients in all databases and in our own cohort. Conclusions We concluded that reduced expression of SPINK4 relates to poor survival in CRC, functioning as a novel indicator.

scholarly journals Elevated ZNF703 Protein Expression Is an Independent Unfavorable Prognostic Factor for Survival of the Patients with Head and Neck Squamous Cell Carcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Hang Yang ◽  
Wen-Qi Jiang ◽  
Ye Cao ◽  
Yong-An Sun ◽  
Jing Wei ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Head And Neck ◽  
Squamous Cell ◽  
The Cancer Genome Atlas ◽  
Cancer Center ◽  
Protein Overexpression ◽  
Prognostic Effect ◽  
Tumor Tissues ◽  
Cancer Genome Atlas

Aim. Data from The Cancer Genome Atlas (TCGA) show that the ZNF703 gene amplifies and overexpresses in head and neck squamous cell carcinomas (HNSCC). However, the clinical relevance of this observation in HNSCC is unclear. The purpose of this study was to clarify the expression of ZNF703 protein and its prognostic effect on HNSCC.Methods. Two hundred ten HNSCC patients from Sun Yat-Sen University Cancer Center with complete survival follow-up were included in this study. Tumor samples from primary sites were collected. The expression of the ZNF703 protein was tested by immunohistochemistry (IHC).Results. The high expression of ZNF703 in HNSCC tumor tissues was significantly higher than that of the matched noncancerous tissues (48.6% versus 11.6%,P<0.001). ZNF703 overexpression was correlated with tumor position (laryngeal carcinoma) and recurrence (allP<0.05). Multivariate analysis revealed that ZNF703 protein overexpression was an independent prognostic factor (P=0.022, hazard ratio = 1.635, 95% CI 1.073–2.493) in HNSCC patients.Conclusion. ZNF703 overexpression is associated with adverse prognosis in HNSCC, which might be a novel biomarker of HNSCC.

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