Genetic Profiling of Stage I and II Colorectal Cancer May Predict Metastatic Relapse

Abstract Background Colorectal cancer is the third most common type of cancer in the world. We characterize a cohort of patients who survived up to 5 years without recurrence and identify factors predicting the probability of cure. Methods We analyzed data of patients who underwent curative intent surgery for stage I–III CRC between 2007 and 2012 and who had had been included in a large multicenter study in the Netherlands. Cure was defined as 5-year survival without recurrence. Survival data were retrieved from a national registry. Results Analysis of data of 754 patients revealed a cure rate of 65% (n = 490). Patients with stage I disease and T1- and N0-tumor had the highest probability of cure (94%, 95% and 90%, respectively). Those with a T4-tumor or N2-tumor had the lowest probability of cure (62% and 50%, respectively). A peak in the mortality rate for older patients early in follow-up suggests early excess mortality as an explanation. A similar trend was observed for stage III disease, poor tumor grade, postoperative complications, sarcopenia, and R1 resections. Patients with stage III disease, poor tumor grade, postoperative complications, sarcopenia, and R1 resections show a similar trend for decrease in CSS deaths over time. Conclusion In the studied cohort, the probability of cure for patients with stage I–III CRC ranged from 50 to 95%. Even though most patients will be cured from CRC with standard therapy, standard therapy is insufficient for those with poor prognostic factors, such as high T- and N-stage and poor differentiation grade.

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Epithelial-Mesenchymal Transition Phenotype, Metformin, and Survival for Colorectal Cancer Patients with Diabetes Mellitus II

Gastroenterology Research and Practice ◽

10.1155/2017/2520581 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Yaodu Wang ◽

Zhiyang Wu ◽

Likuan Hu

Keyword(s):

Diabetes Mellitus ◽

Colorectal Cancer ◽

Epithelial Mesenchymal Transition ◽

Disease Free Survival ◽

Multivariate Regression Analysis ◽

Stage I ◽

Clinicopathological Parameters ◽

Mesenchymal Transition ◽

Patients With Diabetes ◽

E Cadherin

Objectives. We aimed to explore the association between metformin treatment and epithelial-mesenchymal transition (EMT) phenotype and further appraise the prognostic values of metformin and EMT markers E-cadherin and vimentin for colorectal cancer (CRC) in clinical practice. Methods. We collected specimens and evaluated clinicopathological parameters of 102 stage I to III CRC patients with prediagnosed type 2 diabetes mellitus (DM II). Expression of E-cadherin and vimentin in tumors was detected by immunohistochemistry (IHC), and statistical analysis was performed using SPSS 19.0. Results. In correlation tests, we found a lower tumor cell EMT degree (more E-cadherin (P=0.014) and less vimentin (P=0.011) expression in patients who used metformin, and the expression of E-cadherin and vimentin was associated with serum CA19-9 (P=0.048, P=0.009), tumor invasive depth (T) (P<0.001, P=0.045), and lymph invasion (N) (P=0.013, P=0.001). In Cox multivariate regression analysis, E-cadherin was identified as a prognostic factor for disease-free survival (DFS) (P=0.038) and metformin use (P=0.015P=0.044) and lymph invasion (P=0.016P=0.023) were considered as the prognostic factors for both DFS and overall survival (OS). Conclusion. Our study suggested that metformin may impede the EMT process and improve survival for stage I–III CRC patients with DM II.

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A study on the genomic alterations of transformation from colorectal adenoma to colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e15607 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e15607-e15607

Author(s):

Qingjian Chen ◽

Pan Yang ◽

Linna Luo ◽

Wenhua Fan ◽

Chen Wei ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Tissue Sample ◽

Intraepithelial Neoplasia ◽

Stage I ◽

Tissue Samples ◽

Diagnostic Potential ◽

Notch Pathways ◽

Colorectal Cancer Patients ◽

Villous Adenomas

e15607 Background: Colorectal cancer is one of the most common malignancies worldwide. Approximately 85% of colorectal cancers are thought to result from adenoma. However, the molecular mechanism of adenoma transformation into colorectal cancer is still unclear. Methods: Ninety-nine adenoma patients aged from 25 to 78 years old were enrolled in this study. We collected tissue sample from each patient and 77 matched blood samples. Pathological subtypes included tubular villous adenomas, villous adenomas, tubular adenomas, high-grade intraepithelial neoplasia, and polyps. Eighty-one stage I colorectal cancer patients (CRC I) were also enrolled in this study. All samples underwent Next-generation sequencing with a panel of 405 cancer related genes. Results: Mutational profiles of adenoma and CRC I patients were compared. The top 5 most frequently mutated genes in adenoma were APC (71%), KRAS (41%), ATM (33%), RIF1 (31%), SYNE1 (28%). While in CRC I patients, top 5 mutated genes were APC (78%), TP53 (57%), TTN (35%), KRAS (33%) and TCF7L2 (22%). There were significant differences between TP53 and TTN by chi-square test. The frequency, number and TMB of mutations in stage I colorectal cancer patients were significantly higher than those in various adenoma subtypes. Stage I colorectal cancer patients have more mutated genes enriched in the Wnt and Notch pathways than adenoma patients. We analyzed mutation signatures in CRC I and adenoma patients, and CRC I were more focused on mutation signatures of mismatch repair such as signature 1, signature 6, signature 10, and signature 15. A total of 391 mutations were identified in tissue samples, while 130 mutations were found in plasma cell-free DNA, with 116 mutations shared between them. The two genes with the highest consistency between tissue and blood were PAX7 and KMT2D. Conclusions: TP53 and TTN are associated with the transition from CRC I to adenoma, and Wnt and Notch pathways may also be involved. PAX7 and KMT2D mutations frequently found in adenoma tissue and blood cfDNA demonstrate the diagnostic potential of these two genes in clinic.

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The impact of the COVID-19 pandemic on stage at diagnosis of breast and colorectal cancers.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.6501 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 6501-6501

Author(s):

Jade Zhou ◽

Shelly Kane ◽

Celia Ramsey ◽

Melody Ann Akhondzadeh ◽

Ananya Banerjee ◽

...

Keyword(s):

Breast Cancer ◽

Colorectal Cancer ◽

Cancer Screening ◽

Late Stage ◽

Stage Iv ◽

Stage I ◽

Screening Programs ◽

Stage Distribution ◽

Number Of Patients ◽

The Impact

6501 Background: Effective cancer screening leads to a substantial increase in the detection of earlier stages of cancer, while decreasing the incidence of later stage cancer diagnoses. Timely screening programs are critical in reducing cancer-related mortality in both breast and colorectal cancer by detecting tumors at an early, curable stage. The COVID-19 pandemic resulted in the postponement or cancellation of many screening procedures, due to both patient fears of exposures within the healthcare system as well as the cancellation of some elective procedures. We sought to identify how the COVID-19 pandemic has impacted the incidence of early and late stage breast and colorectal cancer diagnoses at our institution. Methods: We examined staging for all patients presenting to UCSD at first presentation for a new diagnosis of malignancy or second opinion in 2019 and 2020. Treating clinicians determined the stage at presentation for all patients using an AJCC staging module (8th edition) in the electronic medical record (Epic). We compared stage distribution at presentation in 2019 vs 2020, both for cancers overall and for colorectal and breast cancer, because these cancers are frequently detected by screening. Results: Total numbers of new patient visits for malignancy were similar in 2019 and 2020 (1894 vs 1915 pts), and stage distribution for all cancer patients was similar (stage I 32% in 2019 vs 29% in 2020; stage IV 26% in both 2019 and 2020). For patients with breast cancer, we saw a lower number of patients presenting with stage I disease (64% in 2019 vs 51% in 2020) and a higher number presenting with stage IV (2% vs 6%). Similar findings were seen in colorectal cancer (stage I: 22% vs 16%; stage IV: 6% vs 18%). Conclusions: Since the COVID-19 pandemic, there has been an increase in incidence of late stage presentation of colorectal and breast cancer, corresponding with a decrease in early stage presentation of these cancers at our institution. Cancer screening is integral to cancer prevention and control, specifically in colorectal and breast cancers which are often detected by screening, and the disruption of screening services has had a significant impact on our patients. We plan to continue following these numbers closely, and will present data from the first half of 2021 as it becomes available.

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S100‐stained perineural invasion is associated with worse prognosis in stage I/II colorectal cancer: Its possible association with immunosuppression in the tumor

Pathology International ◽

10.1111/pin.13195 ◽

2022 ◽

Author(s):

Yumiko Fukuda ◽

Yoshihiro Tanaka ◽

Ken Eto ◽

Natsuko Ukai ◽

Shoko Sonobe ◽

...

Keyword(s):

Colorectal Cancer ◽

Perineural Invasion ◽

Stage I ◽

Worse Prognosis

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Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by a Five Circulating Tumor DNA Methylation Signature in Colorectal Cancer

SSRN Electronic Journal ◽

10.2139/ssrn.3820574 ◽

2021 ◽

Author(s):

Wei Wang ◽

Zhicheng Zeng ◽

Xuecong Zhang ◽

Chengyong Lei ◽

Shaowan Xu ◽

...

Keyword(s):

Colorectal Cancer ◽

Dna Methylation ◽

Early Detection ◽

Therapeutic Efficacy ◽

Circulating Tumor Dna ◽

Metastatic Relapse ◽

Tumor Dna

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POFUT1 as a Promising Novel Biomarker of Colorectal Cancer

Cancers ◽

10.3390/cancers10110411 ◽

2018 ◽

Vol 10 (11) ◽

pp. 411 ◽

Cited By ~ 12

Author(s):

Julien Chabanais ◽

François Labrousse ◽

Alain Chaunavel ◽

Agnès Germot ◽

Abderrahman Maftah

Keyword(s):

Colorectal Cancer ◽

Mucinous Adenocarcinoma ◽

Copy Number ◽

Notch Pathway ◽

Gene Copy Number ◽

Stage I ◽

Gene Copy ◽

Pathway Activation ◽

Potential Biomarker ◽

Cancer Types

Background: While protein O-fucosyltransferase 1 (POFUT1) overexpression has been recently proposed as a potential biomarker for different cancer types, no study was carried out on POFUT1 implication in colorectal cancer (CRC). Methods: Data from 626 tumors and 51 non-tumor adjacent tissues available in FireBrowse had been used in this study. Statistical analyses on POFUT1 expression and gene copy number, NOTCH receptors (main targets of POFUT1 enzymatic activity) expression and association of POFUT1 and NOTCH1 expressions with clinical parameters were investigated. Data were completed by POFUT1 histological labeling on six tumor tissues from patients with CRC. Results: We found that POFUT1 is overexpressed from the stage I (p < 0.001) and 76.02% of tumors have a 20q11.21 amplification, associated in 90.13% of cases with a POFUT1 overexpression, compared to non-tumor adjacent tissues. The POFUT1 copy number in tumors is mainly between 2 and 3. POFUT1 is positively correlated with NOTCH1 (rs = 0.34, p < 0.001), NOTCH3 (rs = 0.087, p = 0.0297), and NOTCH4 (rs = 0.097, p = 0.0148) expressions, while negatively correlated with NOTCH2 expression (rs = −0.098, p = 0.0142). POFUT1 overexpression is markedly associated with rectal location, non-mucinous adenocarcinoma and cancer stages IV and M1. NOTCH1 overexpression is only associated with rectal location and non-mucinous adenocarcinoma. Conclusion: We conclude that POFUT1 is overexpressed in CRC from stage I, and its high expression is associated with metastatic process, probably through NOTCH pathway activation. Then, POFUT1 could represent a potential novel biomarker for CRC diagnosis.

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