Cancer-associated fibroblasts of colorectal cancer and their markers: updates, challenges and translational outlook

2020 ◽  
Vol 16 (29) ◽  
pp. 2329-2344 ◽  
Author(s):  
Marahaini Musa ◽  
Adli Ali

Accumulation of cancer-associated fibroblasts (CAFs) in the tumor microenvironment is associated with poor prognosis and recurrence of colorectal cancer (CRC). Despite their prominent roles in colorectal carcinogenesis, there is a lack of robust and specific markers to classify the heterogeneous and highly complex CAF populations. This has resulted in confusing and misleading definitions of CAFs in cancer niche. Advancements in molecular biology approaches have open doors to reliable CAF marker detection methods in various solid tumors. These discoveries would contribute to more efficient screening, monitoring and targeted therapy of CRC thus potentially will reduce cancer morbidity and mortality rates. This review highlights current scenarios, dilemma, translational potentials of CAF biomarker and future therapeutic applications involving CAF marker identification in CRC.

2019 ◽  
Vol 120 (10) ◽  
pp. 987-995 ◽  
Author(s):  
Xiaowen Xu ◽  
Li Zhu ◽  
Yun Yang ◽  
Yamin Pan ◽  
Zhuo Feng ◽  
...  

2019 ◽  
Vol 6 (1) ◽  
pp. 47-49
Author(s):  
Virgílio Ribeiro Guedes ◽  
Natália Ferreira Bueno ◽  
Victor Vargas de Oliveira ◽  
Maria Cristina da Silva Pranchevicius

RESUMO Introdução: O carcinoma colorretal (CCR) é um tumor que se destaca por suas taxas de incidência e mortalidade no mundo. A maioria dos CRRs se desenvolve a partir de adenomas preexistentes devido a mutações genéticas acumuladas. As mutações no gene TP53 são as mais comuns encontradas nas neoplasias malignas humanas. Sua mutação pode levar ao acúmulo da proteína p53 nuclear, que pode ser vista por métodos de imuno-histoquímica (IHQ). Atualmente, o estadiamento anatomopatológico é principal método utilizado para determinar o prognóstico de pacientes com CCR. Metodologia: Foi realizado um levantamento bibliográfico na base eletrônica PubMed utilizando os descritores: “colorectal cancer” and “p53 protein” and “immunohistochemistry”. Resultados: O CCR é um tumor com altas taxas de incidência e mortalidade no ocidente e oriente. A mutação no gene TP53 parece ser um precursor do CCR e leva ao acúmulo da p53 mutada, que é visível aos métodos de IHQ. A maioria das amostras de CCR apresentaram-se positivas para p53, o que determina um comportamento mais agressivo do tumor e também serve como um fator de prognóstico ruim. Sua superexpressão indica maior chance de metástases e redução da sobrevida. Uma vez que a mutação do TP53 é um evento precoce, a detecção precoce do CCR pode ser feita através da visualização de p53 acumulada sob IHQ. Alterações no gene TP53 são fatores de prognóstico ruim em vários tipos de câncer, incluindo o CCR. Outros marcadores e fenótipos se correlacionam com a p53 no desenvolvimento do CCR, como a vitamina D, o estrogênio e a progesterona. Por fim, em nosso estudo não foi detectado relação entre a expressão da p53, idade, gênero, invasão tumoral, e taxa de regressão. Conclusão: Pode-se inferir que o CCR é um câncer com taxas de incidência, prevalência e mortalidade significantes, e que a IHQ da p53 tem papel importante na detecção precoce e decisão do tratamento. Palavras-chave: Carcinoma colorretal; gene TP53; proteína p53; imuno-histoquímica. ABSTRACT Introduction: Colorectal cancer (CRC) is well known for its incidence and mortality rate. Most of CRCs develops from colonic adenoma, that accumulates genetic mutations. TP53 gene’s mutations are the most common mutations found in human cancers. It’s mutation leads to nuclear p53 accumulation, which can be seen by immunohistochemistry (IHC) methods. Method: A research was done in PubMed using the following words: “colorectal cancer” and “p53 protein” and “immunohistochemistry”. Resulted: The CRC is a tumor with high incidence and mortality rates in the west and in the east. A mutation in TP53 gene seems to be a precursor of the CRC and leads to the accumulation of mutated p53, seen by the IHC methods. Most of CRC samples presents positive p53, and its positivity determinate a more aggressive behavior of the tumor, leading to a poor prognosis. Its overexpression indicates bigger chances of metastasis and survival rate loss. Being an early event, TP53 mutation and the following p53 nuclear accumulation makes the detection of CRC easier by IHC methods. TP53 gene alterations are also poor prognosis factors in various types of cancer, including the CRC. Other marks and phenotypes correlate with p53 in the evolution of CRC, like the vitamin D, estrogen and progesterone. Lastly, it wasn’t detected the relation between age, gender, tumor invasion, neither regression rate. Conclusion: It can be inferred that the CRC is a cancer with significant incidence, prevalence and mortality rates, and that the IHC methods have an important role in the early detection and decision making. Keywords: Colorectal carcinoma; TP53 gene; p53 protein; immunohistochemistry.


2019 ◽  
Author(s):  
Jian Chen ◽  
Guangjian Fan ◽  
Chao Xiao ◽  
Xiao Wang ◽  
Yupeng Wang ◽  
...  

AbstractSerine hydroxymethyltransferase 2 (SHMT2) plays a vital role in one-carbon metabolism and drives colorectal carcinogenesis. In our study, loss of SHMT2 induced 5-Fluorouracil (5-FU) chemoresistance and was associated with poor prognosis in colorectal cancer (CRC). To elucidate the possible mechanism and generate a strategy to sensitize CRC to 5-FU chemotherapy, we first identified the binding proteins of SHMT2 in cancer cells by mass spectrometry. We found that SHMT2 inhibited autophagy through binding cytoplasmic p53. In fact, SHMT2 prevented cytoplasmic p53 degradation by inhibiting the binding of p53 and HDM2. Under treatment with 5-FU, depletion of SHMT2 promoted autophagy and inhibited apoptosis. Autophagy inhibitors CQ decreased low SHMT2-induced 5-FU resistance in vitro and in vivo. Finally, we enhanced the lethality of 5-FU treatment to CRC cells through the autophagy inhibitor or knockdown of SHMT2 in patient-derived and CRC cell xenograft models. Our findings identified the low SHMT2-induced autophagy on 5-FU resistance in CRC. These results reveal SHMT2-p53 as a novel cancer therapeutic target to reduce chemotherapeutic drug resistance.


Swiss Surgery ◽  
2003 ◽  
Vol 9 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Gervaz ◽  
Bühler ◽  
Scheiwiller ◽  
Morel

The central hypothesis explored in this paper is that colorectal cancer (CRC) is a heterogeneous disease. The initial clue to this heterogeneity was provided by genetic findings; however, embryological and physiological data had previously been gathered, showing that proximal (in relation to the splenic flexure) and distal parts of the colon represent distinct entities. Molecular biologists have identified two distinct pathways, microsatellite instability (MSI) and chromosomal instability (CIN), which are involved in CRC progression. In summary, there may be not one, but two colons and two types of colorectal carcinogenesis, with distinct clinical outcome. The implications for the clinicians are two-folds; 1) tumors originating from the proximal colon have a better prognosis due to a high percentage of MSI-positive lesions; and 2) location of the neoplasm in reference to the splenic flexure should be documented before group stratification in future trials of adjuvant chemotherapy in patients with stage II and III colon cancer.


2018 ◽  
Author(s):  
Ying Huang ◽  
Guihua Wang ◽  
Chunmei Zhao ◽  
Rong Geng ◽  
Shu Zhang ◽  
...  

Author(s):  
Sridhar Muthusami ◽  
Ilangovan Ramachandran ◽  
Sneha Krishnamoorthy ◽  
Yuvaraj Sambandam ◽  
Satish Ramalingam ◽  
...  

: The development of colorectal cancer (CRC) is a multi-stage process. The inflammation of the colon as in inflammatory bowel disease (IBD) such as ulcerative colitis (UC) or Crohn’s disease (CD) is often regarded as the initial trigger for the development of CRC. Many cytokines such as tumor necrosis factor alpha (TNF-α) and several interleukins (ILs) are known to exert proinflammatory actions, and inflammation initiates or promotes tumorigenesis of various cancers, including CRC through differential regulation of microRNAs (miRNAs/miRs). miRNAs can be oncogenic miRNAs (oncomiRs) or anti-oncomiRs/tumor suppressor miRNAs, and they play key roles during colorectal carcinogenesis. However, the functions and molecular mechanisms of regulation of miRNAs involved in inflammation-associated CRC are still anecdotal and largely unknown. Consolidating the published results and offering perspective solutions to circumvent CRC, the current review is focused on the role of miRNAs and their regulation in the development of CRC. We have also discussed the model systems adapted by researchers to delineate the role of miRNAs in inflammation-associated CRC.


2020 ◽  
Vol 158 (6) ◽  
pp. S-160
Author(s):  
Hiroki Kobayashi ◽  
Krystyna Gieniec ◽  
Tamsin Lannagan ◽  
Tongtong Wang ◽  
Samuel Asfaha ◽  
...  

2020 ◽  
Vol 86 (5) ◽  
pp. 480-485
Author(s):  
Lior Segev ◽  
Ilana Naboishchikov ◽  
Diana Kazanov ◽  
Ezra Bernstein ◽  
Meital Shaked ◽  
...  

Background CD24 is a sialoglycoprotein anchored to the cell surface via glycosylphosphatidylinositol and is involved in intracellular signaling processes. It plays an important role in the early stages of the multistep process of colorectal carcinogenesis. Several single nucleotide polymorphisms in the CD24 gene are reported to exert a diverse effect on cancer risk. We aimed to elucidate whether CD24 TG/del genetic variants are associated with susceptibility to colorectal cancer (CRC). Methods The study included 179 subjects, 36 with CRC (prior to surgery) and 143 healthy control subjects. Deoxyribonucleic acid was purified from peripheral blood leukocytes, and by using restriction fragment length polymorphism analysis, the CD24 gene was genotyped for the specific genetic variant, TG deletion. Additionally, CD24 protein expression levels were determined by Western blotting analysis. Results The incidence of the TG/del was higher among the CRC patients compared with healthy controls, 14% and 10%, respectively ( P = .54). CD24 protein levels were significantly higher among CRC patients. There were no significant differences in CD24 expression between CRC patients at different stages of the disease or between patients who carry the mutation and those who did not. Conclusions CD24 genetic variant might be of clinical value for risk assessment as part of cancer prevention programs. Further study on larger populations is needed to validate the importance of this dinucleotide deletion in CRC development. Overexpression of CD24 protein occurs early along the multistep process of CRC carcinogenesis, and a simple blood sample based on CD24 expression on peripheral blood leukocytes can contribute to early diagnosis.


2020 ◽  
Vol 10 ◽  
Author(s):  
Lunpo Wu ◽  
Jianfei Fu ◽  
Yi Chen ◽  
Liangjing Wang ◽  
Shu Zheng

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