Lowly Expressed Ribosomal Protein S19 in the Feces of Patients with Colorectal Cancer

Colorectal cancer (CRC) has become one of the most common fatal cancers. CRC tumorigenesis is a complex process involving multiple genetic changes to several sequential mutations or molecular alterations. P53 is one of the most significant genes; its mutations account for more than half of all CRC. Therefore, understanding the cellular genes that are directly or indirectly related to p53 is particularly crucial for investigating CRC tumorigenesis. In this study, a p53-related ribosomal protein, ribosomal protein S19 (RPS19), obtained from the feces of CRC patients is evaluated by using specifically quantitative real-time PCR and knocked down in the colonic cell line by gene silencing. This study found that CRC patients with higher expressions of RPS19 in their feces had a better prognosis and consistent expressions of RPS19 and BAX in their colonic cells. In conclusion, the potential mechanism of RPS19 in CRC possibly involves cellular apoptosis through the BAX/p53 pathway, and the levels of fecal RPS19 may function as a prognostic predictor for CRC patients

A predicted protein, KIAA0247, is a cell cycle modulator in colorectal cancer cells under 5-FU treatment

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is the predominant gastrointestinal malignancy and the leading cause of cancer death. The identification of genes related to CRC is important for the development of successful therapies and earlier diagnosis.</p> <p>Methods</p> <p>Molecular analysis of feces was evaluated as a potential method for CRC detection. Expression of a predicted protein with unknown function, KIAA0247, was found in feces evaluated using specific quantitative real-time polymerase chain reaction. Its cellular function was then analyzed using immunofluorescent staining and the changes in the cell cycle in response to 5-fluorouracil (5-FU) were assessed.</p> <p>Results</p> <p>Gastrointestinal tissues and peripheral blood lymphocytes ubiquitously expressed KIAA0247. 56 CRC patients fell into two group categories according to fecal KIAA0247 mRNA expression levels. The group with higher fecal KIAA0247 (<it>n </it>= 22; ≥ 0.4897) had a significantly greater five-year overall survival rate than the group with lower fecal KIAA0247 (<it>n </it>= 30; < 0.4897) (66.0 ± 11.6%; <it>p </it>= 0.035, log-rank test). Fecal expression of KIAA0247 inversely related to CRC tumor size (Kendall's tau-b = -0.202; <it>p </it>= 0.047). Immunofluorescent staining revealed that the cytoplasm of CRC cells evenly expresses KIAA0247 without 5-FU treatment, and KIAA0247 accumulates in the nucleus after 40 μM 5-FU treatment. In HCT116 p53^-/-cells, which lack p53 cell cycle control, the proportion of cells in the G2/M phase was larger (13%) in KIAA0247-silent cells than in the respective shLuc control (10%) and KIAA0247-overexpressing cells (7%) after the addition of low dose (40 μM) 5-FU. Expression of three cyclin genes (cyclin A2, cyclin B1, and cyclin B2) also downregulated in the cells overexpressing KIAA0247.</p> <p>Conclusions</p> <p>This is the first description of a linkage between KIAA0247 and CRC. The study's data demonstrate overexpression of KIAA0247 associates with 5-FU therapeutic benefits, and also identify the clinical significance of fecal KIAA0247 in CRC.</p

Clinical meaning of age-related expression of fecal cytokeratin 19 in colorectal malignancy

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is one of the leading causes of malignant death worldwide. Because young age of onset is often considered a poor prognostic factor for CRC, it is important to identify the poor outcomes of CRC in a younger population and to consider an aggressive approach by implementing early treatment. Our aim was to specifically quantify the fecal cytokeratin 19 (CK19) transcript from CRC patients and investigate its correlation with clinical stage, tumor malignancy, and age.</p> <p>Methods</p> <p>The quantitation of fecal CK19 transcript was determined by a quantitative real-time reverse transcription polymerase chain in 129 CRC patients (45 younger than 60 years at diagnosis) and 85 healthy controls. The levels of CK19 protein were examined both in colonic cell lines and tissues.</p> <p>Results</p> <p>The analysis of 45 younger CRC patients (age ≤ 60 years) revealed that patients at the M1 stage had significantly higher expression levels of fecal CK19 mRNA when compared with healthy controls (<it>p </it>< 0.001) and patients at the M0 stage (<it>p </it>= 0.004). Additionally, the degree of consistency between the mean level of fecal CK19 mRNA and the distant metastatic rate in each age interval was up to 89% (<it>p </it>= 0.042).</p> <p>Conclusion</p> <p>These results indicate that high levels of fecal CK19 mRNA represent a potential marker for colorectal malignancy and for aggressive treatment of younger CRC patients.</p

Prognostic value of postoperative serum carcinoembryonic antigen levels in colorectal cancer patients who smoke.

Serum carcinoembryonic antigen (CEA) levels can help predict the prognosis of colorectal cancer patients. Accordingly, high preoperative CEA levels that is not restored after surgery are indicative of a worse outcome. On the other hand, smoking can increase serum CEA levels independently of the disease status. Thus, we aimed to evaluate the impact of smoking on the prognostic value of serum CEA levels. This retrospective cohort study included 273 patients who underwent curative resection for stage I-III colorectal adenocarcinoma at a single institution, between January 2010 and December 2017. Patients were grouped as follows: group A, normal preoperative and postoperative CEA levels (n = 152); group B, elevated preoperative CEA levels that returned to reference values after surgery (n = 69); and group C, elevated postoperative serum CEA levels (n = 52). Patients were also grouped according to their smoking history: group S (current smokers, n = 79) and group NS (never and former smokers, n = 194). Group A showed a higher 3-year disease-free survival (DFS) rate (84.9%) than groups B (75.4%) and C (62.0%) (p < 0.001). Postoperative serum CEA levels were significantly higher in the S group than in the NS group (2.6 vs. 3.1 ng/mL, p = 0.009), whereas preoperative levels were similar (3.8 vs. 4.1, p = 0.182). Further, smokers showed higher 3 year-DFS rates than nonsmokers in group C (83.3% vs. 43.9%, p = 0.029). This suggests that while elevated postoperative CEA levels are associated with lower DFS rates in never and former smokers, they are not associated with lower DFS rates in current smokers. We conclude that persistent smoking alters the prognostic value of postoperative serum CEA levels in colorectal cancer patients and that, consequently, alternative surveillance strategies need to be developed for colon cancer patients with smoking habits

Data on clinical significance of GAS2 in colorectal cancer cells

The growth arrest-specific 2 (GAS2) was cloned and found to be upregulated in the feces of recurrent CRC patients. This overexpressed GAS2 induced different patterns of gene expressions in CRC cells. Briefly, one cell proliferation marker, Ki-67 antigen (Ki-67), was upregulated in the cells with overexpressed GAS2, “Correlation between proliferation markers: PCNA, Ki-67, MCM-2 and antiapoptotic protein Bcl-2 in colorectal cancer” [1]. Whereas, the expression of another cell proliferation marker, proliferating cell nuclear antigen (PCNA), changed insignificantly [1]. In addition, the mRNA level of one cyclin involving in both cell cycle G1/S and G2/M transitions was also not affected by GAS2 overexpression, “Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A” [2]. The experimental design and procedures in this article can be helpful for understanding the molecular significance of GAS2 in SW480 and SW620 CRC cells

Concomitant Primary Lung Cancer and Metastatic Pulmonary Colorectal Cancer that Responded to Gemcitabine/Cisplatin/Bevacizumab Combination Therapy

The incidence of double primary malignancy in colorectal cancer is rare (approximately 1-6%), and synchronous double primary malignancy is even rarer for cases involving colorectal cancer. Indeed, its incidence is estimated to be less than 1%. The probability of concurrent colorectal cancer and lung cancer, in particular, is extremely low (approximately 0.1%). In this report, we present such a case of synchronous primary lung cancer and pulmonary metastatic colorectal cancer, which was mistaken for primary lung cancer with lung-to-lung metastasis. Tumors were identified in the upper and lower lobes of right lung. After the patient received a lung cancer chemotherapy, gemcitabine/cisplatin/bevacizumab, the right upper lobe tumor was stable in size, and the right lower lobe tumor regressed. Surprisingly, the right lower lobe tumor was proven to be metastatic colorectal cancer after surgical resection. A primary rectal tumor was then identified through colonoscopy. Subsequently, the patient underwent surgical resection of the primary rectal cancer and chemotherapy. She has now remained disease-free for more than two years

Prognostic Values of EPDR1 Hypermethylation and Its Inhibitory Function on Tumor Invasion in Colorectal Cancer

Aberrant DNA methylation is a potential mechanism underlying the development of colorectal cancer (CRC). Thus, identification of prognostic DNA methylation markers and understanding the related molecular functions may offer a new perspective on CRC pathogenesis. To that end, we explored DNA methylation profile changes in CRC subtypes based on the microsatellite instability (MSI) status through genome-wide DNA methylation profiling analysis. Of 34 altered genes, three hypermethylated (epidermal growth factor, EGF; carbohydrate sulfotransferase 10, CHST10; ependymin related 1, EPDR1) and two hypomethylated (bone marrow stromal antigen 2, BST2; Rac family small GTPase 3, RAC3) candidates were further validated in CRC patients. Based on quantitative methylation-specific polymerase chain reaction (Q-MSP), EGF, CHST10 and EPDR1 showed higher hypermethylated levels in CRC tissues than those in adjacent normal tissues, whereas BST2 showed hypomethylation in CRC tissues relative to adjacent normal tissues. Additionally, among 75 CRC patients, hypermethylation of CHST10 and EPDR1 was significantly correlated with the MSI status and a better prognosis. Moreover, EPDR1 hypermethylation was significantly correlated with node negativity and a lower tumor stage as well as with mutations in B-Raf proto-oncogene serine/threonine kinase (BRAF) and human transforming growth factor beta receptor 2 (TGF&beta;R2). Conversely, a negative correlation between the mRNA expression and methylation levels of EPDR1 in CRC tissues and cell lines was observed, revealing that DNA methylation has a crucial function in modulating EPDR1 expression in CRC cells. EPDR1 knockdown by a transient small interfering RNA significantly suppressed invasion by CRC cells, suggesting that decreased EPDR1 levels may attenuate CRC cell invasion. These results suggest that DNA methylation-mediated EPDR1 epigenetic silencing may play an important role in preventing CRC progression