Is There Currently an Established Role for the Use of Predictive or Prognostic Molecular Markers in the Management of Colorectal Cancer? A Point/Counterpoint

Author(s):  
Alan P. Venook ◽  
Johanna C. Bendell ◽  
Robert S. Warren

Overview: The term “personalized oncology” means different things to the oncologist than to the patient. But fundamentally, the phrase creates the expectation that decisions can be informed by the unique features of the patient and patient's cancer. Much like determining antibiotic sensitivities in urinary tract infections, the oncologist is expected to choose the right treatment(s), for each individual patient. Numerous methods can be used to “personalize” management decisions, although truly useful biomarkers continue to escape our grasp. Positron Emission Tomography in patients with GI stromal tumors or genotyping of c-kit in chronic myelogenous leukemia cells can guide the use of imatinib, these scenarios represent a minority of patients. The promise of individualized therapy, however, has led to the commercialization of numerous assays to probe patient's genetic make-up and that of the tumor. Breast cancer management has benefitted from the analysis of gene recurrence scores. More recently the analysis of germline or tumor-associated mutations in non-small cell lung cancer and melanoma has led to clinically meaningful molecular subsets of these diseases, guiding the successful targeting of such cancers with small-molecule inhibitors. Despite the high incidence of colorectal cancer and our relatively long-standing grasp of the molecular pathways in colorectal carcinogenesis, the management of these patients remains mostly empiric and movement toward “personalization” has been slow and incremental. Now, however, molecular imaging and commercial assays for genetic makeup of tumor specimens has put the oncologist and oncologic surgeon in the crossfire with patients and families who believe the era of “personalization” is here.

Gut ◽  
2020 ◽  
pp. gutjnl-2020-322780
Author(s):  
Jie Hong ◽  
Fangfang Guo ◽  
Shi-Yuan Lu ◽  
Chaoqin Shen ◽  
Dan Ma ◽  
...  

ObjectiveMicrobiota disorder promotes chronic inflammation and carcinogenesis. High glycolysis is associated with poor prognosis in patients with colorectal cancer (CRC). However, the potential correlation between the gut microbiota and glucose metabolism is unknown in CRC.Design18F-FDG (18F-fluorodeoxyglucose) PET (positron emission tomography)/CT image scanning data and microbiota PCR analysis were performed to measure the correlation between metabolic alterations and microbiota disorder in 33 patients with CRC. Multiple colorectal cancer models, metabolic analysis and Seahorse assay were established to assess the role of long non-coding RNA (lncRNA) enolase1-intronic transcript 1 (ENO1-IT1) in Fusobacterium (F.) nucleatum-induced glucose metabolism and colorectal carcinogenesis. RNA immunoprecipitation and chromatin immunoprecipitation sequencing were conducted to identify potential targets of lncRNA ENO1-IT1.ResultsWe have found F. nucleatum abundance correlated with high glucose metabolism in patients with CRC. Furthermore, F. nucleatum supported carcinogenesis via increasing CRC cell glucose metabolism. Mechanistically, F. nucleatum activated lncRNA ENO1-IT1 transcription via upregulating the binding efficiency of transcription factor SP1 to the promoter region of lncRNA ENO1-IT1. Elevated ENO1-IT behaved as a guider modular for KAT7 histone acetyltransferase, specifying the histone modification pattern on its target genes, including ENO1, and consequently altering CRC biological function.ConclusionF. nucleatum and glucose metabolism are mechanistically, biologically and clinically connected to CRC. Targeting ENO1 pathway may be meaningful in treating patients with CRC with elevated F. nucleatum.


2015 ◽  
Vol 61 (2) ◽  
pp. 71-74
Author(s):  
A Dobre ◽  
A Hintea ◽  
L Azamfirei

Abstract Objective: We attempt to evaluate how the European treatment guides are implemented in a clinic hospital in Targu Mures and if those rules could be adopted as they are or must be adapted to our national specificity. Methods: For a number of 441 patients included in the study, the electronic prospectively maintained archive of 3rd Surgery was interrogated for: age, preoperative colonoscopy, postoperative colonoscopies, chemo-radiotherapy enrollment, stage of the disease, type of surgery. Local and regional relapses were assessed and their incidence was related to type of surgery. Survival analysis was done in a simplified manner and differentiated for age below and above 75 years. Results: Patient’s age distribution revealed a deviation to the right compared with a normal distribution with a median off 64.76±11.47. Colonoscopy was done in only 65 cases, exclusive preoperatively. Chemoradiotherapy was administered in 168 cases, only 12 of them initiated preoperatively. The type of surgery performed was found positively correlate with the stage of the disease. The survival probability for the patients in this study showed a 50% survival rate at 1 year and only 2% at 5 years. Conclusions: Passive screening age in CRC should be decreased to 55 years. Stage 3 and 4 of disease for CRC are over 70% of cases, like 20 years ago. Survival rate in CRC is far lower than other studies. Integrated CRC management and European practical guides are still “in wishing” stage.


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.


2002 ◽  
Vol 13 (2) ◽  
pp. 127-138
Author(s):  
Ronan McDermott ◽  
Farrokh Dehdashti ◽  
Barry A. Siegel

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.


2019 ◽  
Vol 13 (1) ◽  
pp. 58-65
Author(s):  
Takashi Tashiro ◽  
Fumihiro Uwamori ◽  
Yukiomi Nakade ◽  
Tadahisa Inoue ◽  
Yuji Kobayashi ◽  
...  

Gastrointestinal stromal tumors (GISTs) are known to originate specifically from the intestinal cells of Cajal located in the gastrointestinal mesenchyme. GISTs developing outside of the digestive tract have barely been reported. We encountered a first case of large primary GISTs in the liver with cystic changes. A 63-year-old man with a past history of brain infarction visited our hospital. The computed tomography (CT) revealed a 6-cm and a 10-cm mass in the right and the caudal lobe of the liver, respectively. These tumors have marginal enhancement in the arterial phase; however, they presented as hypodense in the internal tumor sites. Both liver tumors had cystic changes. Gastrointestinal examinations using endoscopy revealed no other gastrointestinal tumors, and [18F]-fluoro-2-deoxy-D-glucose positron emission tomography/CT revealed multiple bone metastases in addition to the liver tumors. The liver tumor specimens were composed of spindle cells, and the immunohistochemical staining for c-Kit and for DOG1, as discovered on GIST, was positive. The patient was diagnosed with primary hepatic GIST with cystic changes.


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.


2015 ◽  
Vol 87 (9) ◽  
Author(s):  
Łukasz Dziki ◽  
Anna Puła ◽  
Konrad Stawiski ◽  
Barbara Mudza ◽  
Marcin Włodarczyk ◽  
...  

Abstractwas to assess patients’ awareness of the prevention and treatment of colorectal cancer.Patients diagnosed with colorectal cancer, hospitalised at the Department of General and Colorectal Surgery of the Medical University in Łódź during the period from January 2015 to April 2015, were asked to complete a questionnaire concerning their families’ medical case record, factors predisposing them to the development of colorectal cancer, the tests applied in diagnostics, and the treatment process. The questionnaire comprised 42 closed-ended questions with one correct answer. A statistical analysis of all answers was carried out.The study group consisted of 30 men and 20 women aged 27–94 years old. A strong, statistically significant negative correlation between a patient’s age and his/her awareness of the prevention and treatment of colorectal cancer was noted (p<0.001; r= −0.51). The study demonstrated a statistically significant relationship between the occurrence of neoplasms in a patient’s family (p=0.009) or, more specifically, the occurrence of colorectal cancer (p=0.008), and the awareness of the prevention programme. The women’s group was characterised by statistically significantly greater awareness of colonoscopy as a screening examination (p=0.004).Patients need more information on colorectal cancer, its risk factors, prevention, the treatment process, and postoperative care. Lack of awareness of the colorectal cancer issue can be one of the major factors contributing to the high incidence of this disease.


Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1493
Author(s):  
Camila Meirelles S. Silva ◽  
Mateus C. Barros-Filho ◽  
Deysi Viviana T. Wong ◽  
Julia Bette H. Mello ◽  
Livia Maria S. Nobre ◽  
...  

Colorectal cancer (CRC) is a disease with high incidence and mortality. Colonoscopy is a gold standard among tests used for CRC traceability. However, serious complications, such as colon perforation, may occur. Non-invasive diagnostic procedures are an unmet need. We aimed to identify a plasma microRNA (miRNA) signature for CRC detection. Plasma samples were obtained from subjects (n = 109) at different stages of colorectal carcinogenesis. The patients were stratified into a non-cancer (27 healthy volunteers, 17 patients with hyperplastic polyps, 24 with adenomas), and a cancer group (20 CRC and 21 metastatic CRC). miRNAs (381) were screened by TaqMan Low-Density Array. A classifier based on four differentially expressed miRNAs (miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p) was able to discriminate cancer versus non-cancer cases. The overexpression of these miRNAs was confirmed by RT-qPCR, and a cross-study validation step was implemented using eight data series retrieved from Gene Expression Omnibus (GEO). In addition, another external data validation using CRC surgical specimens from The Cancer Genome Atlas (TCGA) was carried out. The predictive model’s performance in the validation set was 76.5% accuracy, 59.4% sensitivity, and 86.8% specificity (area under the curve, AUC = 0.716). The employment of our model in the independent publicly available datasets confirmed a good discrimination performance in five of eight datasets (median AUC = 0.823). Applying this algorithm to the TCGA cohort, we found 99.5% accuracy, 99.7% sensitivity, and 90.9% specificity (AUC = 0.998) when the model was applied to solid colorectal tissues. Overall, we suggest a novel signature of four circulating miRNAs, i.e., miR-28-3p, let-7e-5p, miR-106a-5p, and miR-542-5p, as a predictive tool for the detection of CRC.


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