TRPM7 is overexpressed in human IBD-related and sporadic colorectal cancer and correlates with tumor grade

Background: The DNA mismatch repair (MMR) system is one of the molecular pathways involved in colorectal cancer (CRC) carcinogenesis that consists of several genes, including MLH1 (MutL homolog 1), MSH6 (MutS homolog 6), MSH2 (MutS homolog 2), and MSH3 (MutS homolog 3). The protein encoded by PMS2 (post-meiotic segregation 2) is also essential for MMR. Here, we address the correlation between immunohistochemical and transcriptional expression of PMS2 with the tumor grade and clinical stage of non-hereditary/sporadic CRC disease. Methods: This study retrospectively analyzed 67 colorectal resections performed for 38 male and 29 female patients. Random biopsies were taken by a gastroenterologist from patients referring to three hospitals in the cities of Zanjan, Urmia and Qazvin (Iran) during 2017-2019. All specimens were examined and classified for localization of tumor, pathological stage and grade. The PMS2 protein expression was studied immunohistochemically and analysis of mRNA expression was performed in the same tissue sections. Results: Immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) analysis showed a decrease in PMS2 expression compared with paracancerous tissue (P<0.001), which correlated with tumor stage. In addition, reduced PMS2 expression was correlated with the tumor differentiation grade, underlining a connection between downregulation of PMS2 and progression of CRC. Comparing the PMS2 mRNA levels in different groups showed the following results: 0.92 ± 0.18 in patients with Stage I CRC tumor, 0.86 ± 0.38 in Stage Ⅱ, 0.50 ± 0.29 in Stage Ⅲ, and 0.47 ± 0.23 in Stage Ⅳ. Conclusion: These findings suggest that PMS2 may provide a potential reliable biomarker for CRC classification by combined immunohistochemical and mRNA analysis.

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Heterogeneity of KRAS, NRAS, PIK3CA and BRAF mutational status in primary tumour, lymph nodes and liver metastases in sporadic colorectal cancer

10.26226/morressier.5b4709896f4cb30010951e82 ◽

2018 ◽

Author(s):

Sofia Del Carmen

Keyword(s):

Colorectal Cancer ◽

Lymph Nodes ◽

Liver Metastases ◽

Primary Tumour ◽

Sporadic Colorectal Cancer ◽

Mutational Status

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Clinicopathologic Features of Sporadic Colorectal Cancer with MLH1/MSH2 Loss of Expression - Reduced Likelihood of Metastases

Journal of the Korean Society of Coloproctology ◽

10.3393/jksc.2008.24.3.175 ◽

2008 ◽

Vol 24 (3) ◽

pp. 175 ◽

Cited By ~ 3

Author(s):

Ji Won Park ◽

Hee Jin Chang ◽

Kyung Hae Jung ◽

Dae Yong Kim ◽

Dae Kyung Sohn ◽

...

Keyword(s):

Colorectal Cancer ◽

Sporadic Colorectal Cancer ◽

Clinicopathologic Features

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Faculty Opinions recommendation of Prognostic significance of lymphovascular invasion in sporadic colorectal cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3403956.3098054 ◽

2010 ◽

Author(s):

Heidi K Chua

Keyword(s):

Colorectal Cancer ◽

Lymphovascular Invasion ◽

Prognostic Significance ◽

Sporadic Colorectal Cancer

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Biomarkers for Early Detection of Colitis-associated Colorectal Cancer - Current Concepts, Future Trends

Current Drug Targets ◽

10.2174/1389450121666200220123844 ◽

2020 ◽

Vol 22 (1) ◽

pp. 137-145

Author(s):

Tomasz Mackiewicz ◽

Aleksander Sowa ◽

Jakub Fichna

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Cancer Development ◽

Sporadic Colorectal Cancer ◽

Future Trends ◽

Significant Progress ◽

Current Standard ◽

Risk Of Cancer ◽

Histological Testing ◽

Made In

: Colitis-associated colorectal cancer (CAC) remains a critical complication of ulcerative colitis (UC) with mortality of approximately 15%, which makes early CAC diagnosis crucial. The current standard of surveillance, with repetitive colonoscopies and histological testing of biopsied mucosa samples is burdensome and expensive, and therefore less invasive methods and reliable biomarkers are needed. Significant progress has been made thanks to continuous extensive research in this field, however no clinically relevant biomarker has been established so far. This review of the current literature presents the genetic and molecular differences between CAC and sporadic colorectal cancer and covers progress made in the early detection of CAC carcinogenesis. It focuses on biomarkers under development, which can be easily tested in samples of body fluids or breath and, once made clinically available, will help to differentiate between progressors (UC patients who will develop dysplasia) from non-progressors and enable early intervention to decrease the risk of cancer development.

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Tracking the Antibody Immunome in Sporadic Colorectal Cancer by Using Antigen Self-Assembled Protein Arrays

Cancers ◽

10.3390/cancers13112718 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2718

Author(s):

María González-González ◽

José María Sayagués ◽

Luis Muñoz-Bellvís ◽

Carlos Eduardo Pedreira ◽

Marcello L. R. de Campos ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Utility ◽

Genetic Alterations ◽

Western World ◽

Sporadic Colorectal Cancer ◽

Protein Arrays ◽

Humoral Immune ◽

Cellular Processes ◽

Healthy Donors ◽

Associated Proteins

Sporadic Colorectal Cancer (sCRC) is the third leading cause of cancer death in the Western world, and the sCRC patients presenting with synchronic metastasis have the poorest prognosis. Genetic alterations accumulated in sCRC tumor cells translate into mutated proteins and/or abnormal protein expression levels, which contribute to the development of sCRC. Then, the tumor-associated proteins (TAAs) might induce the production of auto-antibodies (aAb) via humoral immune response. Here, Nucleic Acid Programmable Protein Arrays (NAPPArray) are employed to identify aAb in plasma samples from a set of 50 sCRC patients compared to seven healthy donors. Our goal was to establish a systematic workflow based on NAPPArray to define differential aAb profiles between healthy individuals and sCRC patients as well as between non-metastatic (n = 38) and metastatic (n = 12) sCRC, in order to gain insight into the role of the humoral immune system in controlling the development and progression of sCRC. Our results showed aAb profile based on 141 TAA including TAAs associated with biological cellular processes altered in genesis and progress of sCRC (e.g., FSCN1, VTI2 and RPS28) that discriminated healthy donors vs. sCRC patients. In addition, the potential capacity of discrimination (between non-metastatic vs. metastatic sCRC) of 7 TAAs (USP5, ML4, MARCKSL1, CKMT1B, HMOX2, VTI2, TP53) have been analyzed individually in an independent cohort of sCRC patients, where two of them (VTI2 and TP53) were validated (AUC ~75%). In turn, these findings provided novel insights into the immunome of sCRC, in combination with transcriptomics profiles and protein antigenicity characterizations, wich might lead to the identification of novel sCRC biomarkers that might be of clinical utility for early diagnosis of the tumor. These results explore the immunomic analysis as potent source for biomarkers with diagnostic and prognostic value in CRC. Additional prospective studies in larger series of patients are required to confirm the clinical utility of these novel sCRC immunomic biomarkers.

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Actual survival after resection of primary colorectal cancer: results from a prospective multicenter study

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02207-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Inge van den Berg ◽

Robert R. J. Coebergh van den Braak ◽

Jeroen L. A. van Vugt ◽

Jan N. M. Ijzermans ◽

Stefan Buettner

Keyword(s):

Colorectal Cancer ◽

Postoperative Complications ◽

Multicenter Study ◽

Survival Data ◽

Standard Therapy ◽

Tumor Grade ◽

National Registry ◽

Stage I ◽

Stage Iii ◽

Curative Intent

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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