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Cancer is a major disease and the leading cause of death worldwide, with colorectal cancer (CRC) being the third-most common cancer in Korea. The survival rate associated with CRC reduces as the disease stage increases. Therefore, its early detection and treatment can greatly increase patient survival rates. In this study, we identified the tetraspanin 5 (TSPAN5) gene as an important biomarker for predicting the prognosis of patients with CRC. A TMA slide was used for statistical analysis. pN and clinical stage were found to be significant factors according to chi-square analysis, whereas pT, pN, metastasis, clinical stage, and TSPAN5 expression were significant according to Cox regression analysis. In order to prove the usefulness of TSPAN5, which is overexpressed in patients with metastatic CRC, as a biomarker, proliferation, migration, invasion, and tumorigenicity were examined using cell lines inhibited using small interfering RNA. The evaluations confirmed that TSPAN5 suppression, in turn, suppressed proliferation, migration, invasion, and tumorigenesis, which are characteristic of cancer cells. Therefore, the evaluation of TSPAN5 expression may help observe the prognosis of CRC and determine an appropriate treatment method for patients with CRC.

Patients with colorectal cancer (CRC) often fail to complete full-course chemotherapy with a standard dose due to various reasons. This study aimed to determine whether body composition affects chemotherapy adherence in patients with CRC. The medical records of 107 patients with stage III CRC who underwent adjuvant folinic acid, fluorouracil and oxaliplatin (FOLFOX) chemotherapy at a single center between 2014 and 2018 were analyzed retrospectively. Blood test results for selected immunonutritional markers were analyzed and body composition was measured through computed tomography. Univariate and multivariate analyses were performed on low and high relative dose intensity (RDI) groups, based on an RDI of 0.85. In the univariate analysis, a higher skeletal muscle index was correlated with a higher RDI (p = 0.020). Psoas muscle index was also higher in patients with high RDI than in those with low RDI (p = 0.026). Fat indices were independent of RDI. Multivariate analysis was performed for the aforementioned factors and results showed that age (p = 0.028), white blood cell count (p = 0.024), and skeletal muscle index (p = 0.025) affected RDI. In patients with stage III CRC treated with adjuvant FOLFOX chemotherapy, a decrease in RDI was related to age, white blood cell count, and skeletal muscle index. Therefore, if we adjust the drug dosage in consideration of these factors, we can expect an increased treatment efficiency in patients by increasing chemotherapy compliance.

Uncovering tumor markers of colorectal cancer is important for the early detection and prognosis of the patients. Spermine oxidase (SMOX) is upregulated in various cancers. The present study aims to explore the biologic function and expression patterns of SMOX in colorectal cancer (CRC), the third most common type of cancer worldwide. We used quantitative real-time PCR, Western blot, and in vitro functional studies in four CRC cell lines knocked down by SMOX siRNA and immunohistochemistry in 350 cases of CRC tissues. The results showed that SMOX was overexpressed in CRC cell lines and clinical samples. SMOX overexpression in tumor tissues was an independent prognostic factor, worsening overall survival (p = 0.001). The knock-down of SMOX inhibited CRC cell proliferation, invasion, and soft agar colony formation, uncovering its carcinogenic functions. This study indicated that SMOX overexpression could be an important oncogene in CRC and might serve as a valuable prognostic marker and potential therapeutic target for CRC.

Pt-based drugs are one of the main active agents in colorectal cancer treatment. However, drug resistance and dose-dependent side effects are the main barriers that restrict their clinical applications. As an alternative approach to these issues, we designed and synthesized a cell penetrating peptide (CPP) octaarginine-oxaliplatin conjugate that quickly and successfully delivered oxaliplatin into colon cancer cells. The CPP octaarginine is a well-studied cationic peptide that can play a role as a drug delivery vector. In this work, an octaarginine CPP (RRRRRRRR) was conjugated with oxaliplatin via a specific heterobifunctional linker. The in vitro studies showed the conjugate had affinity toward mitochondria inside cells and the MTT assay confirmed that conjugate is active in low micromolar range against colon cancer cells, requiring much lower concentrations than the oxaliplatin alone to reach IC50. More importantly, in the in vivo mouse study, the conjugate effectively inhibited tumor growth and showed considerably high antitumor activity, demonstrating the conjugate can perform well in vivo. This strategy may offer a new approach for designing oxaliplatin derivatives or prodrugs with remarkable therapeutic capabilities.

Inactivation of the ten-eleven translocation (TET) family members and catalyzation of 5-methylcytosine (5-mC) into 5-hydroxymethylcytosine (5-hmC) is associated with cancer initiation and progression. AMP-activated protein kinase (AMPK) is an enzyme that stabilizes TET2; however, the clinical relevance of AMPK and TET2 expression levels is currently unclear. Therefore, the present study aimed to investigate the clinical implications of AMPK/TET2 expression levels in colorectal cancer (CRC). Immunohistochemistry was used to retrospectively examine the expression levels of AMPK and TET2 in paraffin-embedded specimens obtained from 343 patients with CRC. The results demonstrated that AMPK and TET2 were highly expressed in CRC samples. No significant association was observed between the expression levels of TET2 and patient clinicopathological characteristics (age, tumor location, lymphatic, vascular and perineural invasion, Tumor-Node-Metastasis stages and differentiation); however, patients with low expression levels of TET2 more frequently presented with distant metastasis. By contrast, the expression levels of AMPK were significantly associated with lymph node and distant metastases. The survival analysis results revealed that high expression levels of TET2 were an independent predictor of favorable prognosis compared with low TET2 levels. However, no significant differences in overall survival were observed between patients with high and low expression levels of AMPK. These results described the clinical significance of AMPK/TET2 in CRC. The results of the multivariate analysis demonstrated that high expression levels of TET2 were a predictor of a favorable prognosis, whereas AMPK was not a significant factor for determining patient prognosis; therefore, further functional analysis of AMPK/TET2 expression in CRC is needed.

HJURP is a key factor for CENP-A deposition and maintenance in centromeres. The role of mis-regulation of histone chaperones in cancer initiation and progression has been studied. However, its role in colorectal cancer is still unclear. In this study, we aimed to evaluate the expression of HJURP in 162 colorectal cancer tissue. To investigate the function of HJURP in the colorectal cancer cell, we suppressed HJURP expression by siRNA and confirmed proliferation, migration, invasion, and anchorage independent of colony forming ability. The association between HJURP expression levels and clinicopathological factors was evaluated in 162 CRC tissues using immunohistochemistry. The overall survival rate in patients of HJURP high expression was higher than those in HJURP low expression in CRC. Suppressing HJURP expression decreased cellular proliferation, invasion, and migration in four CRC cell lines: HT29, HCT116, SW480, SW620 in vitro study. Our findings revealed that the knockdown of HJURP suppressed the proliferation, migration, invasion, and tumorigenicity in CRC cells. Due to its strong association with CRC, HJURP could be a potential prognostic biomarker and a novel target for drug discovery.

OBJECTIVE This study investigated the relationship of fluorine-18-fluorodeoxyglucose (F-FDG) uptake of bone marrow (BM) on PET/computed tomography (PET/CT) with clinicopathologic factors and survival in patients with colorectal cancer. PATIENTS AND METHODS The study retrospectively included 226 patients with colorectal cancer who underwent F-FDG PET/CT for staging workup and treated with curative surgical resection. The maximum F-FDG uptake of primary cancer (Tmax) and mean F-FDG uptake of BM [BM standardized uptake value (SUV)] were derived from PET/CT images. The relationships between BM SUV and clinicopathologic factors and prognostic value of BM SUV for predicting recurrence-free survival (RFS) were assessed. RESULTS Patients with T3-T4 stage and hepatic metastases had significantly higher values of BM SUV than those with T1-T2 stage and no distant metastases (P

To determine the relationship between metabolic activity of adipose tissue on FDG PET/CT and prognosis in colorectal cancer. A total of 176 colorectal cancer patients with curative surgical resection were retrospectively enrolled. Volume and metabolic activity of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on FDG PET/CT images were measured. The maximum standardized uptake value (SUV) of primary tumor (SUVtumor) was also obtained. Univariate analysis with log-rank test and multivariate Cox regression analyses were used to evaluate prognostic values of volume and metabolic activity of SAT and VAT as well as SUVtumor and clinicopathologic factors. Of 176 patients, 26 experienced recurrence during follow-up. SUVtumor showed significant correlation with serum C-reactive protein level (r = 0.242, p = 0.001), SUV of VAT (r = 0.167, p = 0.026), and size of primary tumor (r = 0.341, p

Adjuvant chemotherapy (AC) is frequently considered in patients with high-risk stage II colorectal cancer (CRC). Among patients with stage II CRC who do not receive AC because they are not considered to be at high risk, 20–25% will develop recurrence and die from the disease. Elevated levels of KPNA2 have been observed in various cancers, and overexpression of KPNA2 is related to CRC progression. We examined the expression of KPNA2 using 293 CRC tissues, including 118 with stage II CRC, and investigated the applicability of KPNA2 as a biomarker to predict high-risk stage II CRC. Moreover, we further investigated the role of KPNA2 as an oncogene in CRC carcinogenesis using in vitro functional studies. High KPNA2 expression was associated with vascular (p = 0.027) and lymphatic invasion (p = 0.009) in patients with stage II CRC. On multivariate analysis, high KPNA2 expression (HR 3.174, 95% CI 2.060–4.889; p

Angiopoietin-2 (Ang-2) has been investigated in cancer primarily in terms of its angiogenic function, and its role as an oncogene has yet to be elucidated. The current study hypothesized that Ang-2 may be an oncogene and have a function in tumor progression. An investigation of the function of Ang-2 in the LoVo colorectal cancer (CRC) cell line in vitro, which expresses a high level of Ang-2, was performed by knocking down endogenous expression with a targeted short hairpin RNA. The aggressive phenotypic effects of Ang-2 on experimental and control group cells were assessed using cell proliferation, migration and invasion assays. The association between Ang-2 expression levels and clinicopathological factors was evaluated in 415 CRC tissues using immunohistochemistry. Suppressing Ang-2 expression decreased cellular proliferation, invasion and migration in an in vitro study. Ang-2 overexpression was observed in 46% of patients with CRC and was significantly associated with pT (P=0.048), pN (P

Defensin alpha 6 (DEFA6) is a member of the alpha defensin family of microbicidal and cytotoxic peptides that defend against bacteria and viruses. Here, we provide a novel function of DEFA6 in tumorigenesis of colorectal cancer (CRC) in vitro and in vivo. Specifically, DEFA6 is highly expressed in both CRC cancer cell lines as well as patient-derived samples at the level of RNA and protein. By shRNA-mediated loss of function of DEFA6, we found that proliferation, migration, invasion, colony forming ability of CRC cell lines were impaired in the absence of DEFA6 in vitro. Furthermore, DEFA6-deficient cancer cells exhibited significantly reduced growth rates compared to control cells in vivo. More importantly, by analyzing 352 patient-derived samples, we revealed that DEFA6 is associated with overall survival rate of CRC patients and thus an independent prognostic marker for CRC. These results suggest that DEFA6 plays an essential oncogenic role in CRC and serves a good therapeutic target for the disease.

Purpose Angiopoietin-1 (Ang-1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor, Tie-2. Increased levels of Ang-2 have been shown to be correlated with abnormal tumor angiogenesis in several malignancies. Hence, we estimated the increased expression of Ang-2 relative to Ang-1 in patients with colorectal cancer and correlated our finding with prognosis in order to investigate the relationships between the expressions of Ang-1/Ang-2/Tie-2 receptor and the clinical parameters or overall survival of such patients. Methods We retrospectively analyzed 114 tissue samples from patients with colorectal cancer by using immunohistochemistry (IHC) to examine Ang-1, Ang-2, and Tie-2 expressions and to investigate the relationship between those expressions and clinical parameters or overall survival of such patients. A Western blot analysis was used for Ang-2 expression. Results IHC staining showed a link between Ang-1 and Tie-2 (P = 0.018), as well as meaningful correlations between Ang-2 and Tie-2 receptor (P = 0.022) and between lymph-node metastasis and Ang-2 (P = 0.025). The stronger the IHC staining for Ang-2 expression was, the shorter the cumulative survival was (P = 0.016). Conclusion A relationship was found to exist between Ang-2 and Tie-2 expressions. The Ang-2 was correlated with lymph-node metastasis, and high expression of Ang-2 was indicative of poor overall survival. These findings suggest that Ang-2 is a useful prognostic marker in the management of patients with colorectal cancer. In addition, we suggest that Ang/Tie-2 signaling plays an important role in the progression of colorectal cancer.

Primary malignant peripheral nerve sheath tumor (MPNST) in a young female patient, not associated with neurofibromatosis type-I is extremely rare in the liver. A 33-year-old female was admitted with a right flank pain for a weak. The CT scan showed 12.5-cm-sized mass located at the right hepatic lobe. At laparotomy, about 20.0-cm-sized mass was on the right hepatic lobe with attachment to right diaphragmatic pleura. Right hepatic lobe and adherent part of diaphragmatic pleura were resected. On histology and immunohistochemistry, it was diagnosed MPNST. Adjuvant radiotherapy for the right diaphragmatic pleura and adjuvant chemotherapy with adriamycin, ifosfamide and cisplatin were sequentially performed. The prognosis of MPNST is generally poor and it is associated with a highly aggressive course of recurrence, metastases, and death. Our case is probably a first report about combination therapy.

Alimentary tract duplications are uncommon congenital anomalies that usually present during the first decade of life. Complete duplication of the colon in adults is very rare and difficult to diagnose preoperatively. We report a case of a 40-year-old female with complete tubular duplication which was initially misdiagnosed as a salpingeal abscess due to colovaginal fistula.

The protein kinase, membrane‑associated tyrosine/threonine 1 (PKMYT1) is known to inhibit precocious entry into mitosis by phosphorylating CDK1 at Thr14 and Tyr15 residues. However, the functional importance of PKMYT1 in colorectal cancer (CRC) remains unknown. Thus, it is important to elucidate whether PKYMT1 is indispensable in the tumorigenesis of CRC. To investigate the functional importance of PKMYT1 in CRC tumorigenesis, PKMYT1 was knocked down in CRC cell lines such as SW480, SW620, HCT116 and HT29 by siRNA. PKMYT1‑depleted CRC cells were analyzed to determine proliferation, migration, invasion and colony forming ability. In addition, 179 patient‑derived samples were used to find the correlation of the expression of PKMYT1 with the prognosis of CRC patients. By siRNA‑mediated loss of function of PKMYT1, we observed that proliferation, migration, invasion and colony forming ability of CRC cell lines were significantly impaired in the absence of PKMYT1 in vitro. Furthermore, by analyzing patient‑derived samples, we revealed the association of PKMYT1 with the overall survival rate of CRC patients. These results indicated that PKMYT1 plays an essential oncogenic role in CRC and could serve as a good therapeutic target for the treatment of CRC.

Purpose Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC. Methods Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining. Results Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363). Conclusion Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

Solute carrier organic anion transporter family member 4A1 (SLCO4A1) is involved in the transport of various compounds, including sugars, bile salts, organic acids, metal ions, amine compounds, and estrogen. SLCO4A1 is highly expressed in several cancers and a gender bias has been observed in colorectal cancer (CRC). We investigated SLCO4A1 expression, its prognostic value in patients with CRC, and its role in CRC cell proliferation and metastasis. SLCO4A1 expression was assessed by immunohistochemistry (IHC) on specimens from 84 patients with CRC. The association of SLCO4A1 expression with clinicopathological features was examined. To confirm the biological role of SLCO4A1 in CRC, four CRC cell lines expressing SLCO4A1 were used and SLCO4A1 expression was knocked down by siRNA. Cell proliferation, MTT, migration, invasion, and semisolid agar colony formation assays were performed. SLCO4A1 was overexpressed in 32% of the CRC samples. SLCO4A1 overexpression and pathologic T stage were independent prognostic factors of decreased survival (P = 0.021). Kaplan–Meier analysis indicated a decreased cumulative survival for patients highly expressing SLCO4A1 compared to patients showing low SLCO4A1 expression (Log-rank test, P = 0.025). In cell lines, SLCO4A1 knockdown resulted in a significant decrease of viability, invasion, and migration when compared to control cells. Semisolid colony formation assay indicated that SLCO4A1-knocked down cells presented poor carcinogenic abilities compared to control cells. SLCO4A1 may be a valuable marker of poor prognostic for CRC. Furthermore, SLCO4A1 plays an important role in CRC cell proliferation, migration, invasion, and carcinogenesis.

Purpose: Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family. PlGF is implicated in several pathologic processes, including the growth and spread of cancer and tumor angiogenesis. The aim of this study was to evaluate the expression and the clinical implications of PlGF in colorectal cancer. Methods: In order to ascertain the clinical significance of PlGF expression in colorectal cancer, the researcher analyzed the expression pattern of PlGF by using an immunohistochemical method and attempted to establish if a relationship existed between PlGF expression and microvessel density (MVD), and subsequently between PlGF expression and the predicted prognosis. A total of 83 patients with colorectal cancer were included for immunohistochemical staining. Clinicopathological characteristics were defined according to the tumor-node-metastasis (TNM) criteria of the Union for Inter national Cancer Control. Clinicopathologic factors, such as age, sex, histological types of tumors, tumor cell grade, TNM stage, lymphovascular invasion, and lymph-node metastasis, were reviewed. Results: In this study, the PlGF protein expression level was significantly correlated with MVD, patient survival, and clini copathological factors such as lymph-node metastasis, TNM staging, lymphatic invasion and vascular invasion. Conclusion: PlGF may be an important angiogenic factor in human colorectal cancer, and in this study, PlGF expression level was significantly correlated with positive lymph-node metastases, tumor stage, and patient survival. These findings suggest that PlGF expression correlates with disease progression and may be used as a prognostic marker for colorectal cancer.

Purpose : Perineural invasion (PNI) is widely known to be correlated with poor survival in many type of malignancy but the connection between perineural invasion of colorectal cancer and the prognosis has not yet been clearly confirmed. Therefore, we examined perineural invasion in colorectal cancers and investigated its relationship to clinicopathological features such as tumor staging, lymph node metastasis, vascular invasion, lymphatic invasion and patient’s prognosis in this study Methods : The subjects were 148 colorectal cancer patients who underwent surgical resection in OOO. The pathologists who were not aware of the prognosis of the patients reexamined the existing biopsy results and reevaluated the perineural invasion. The presence of perineural invasion and the other clinicopathological factors were compared and the statistical significance of the correlation between these was examined. Results : Perineural invasion was confirmed in less than 10% of the patients in the initial biopsy results. However, it was confirmed in 20.9% of the patients reevaluating the biopsy. Perineural invasion in colorectal cancer was found to be unrelated to the T stage of the patients (p=0.114). On the other hand, perineural invasion appeared to be strongly related to lymph node metastasis of colorectal cancer (p more common in the patients with perineural invasion (p=0.001). Moreover, perineural invasion seemed to be related to the stage of cancer (p the level of differentiation nor to the distant metastasis since perineural invasion was expressed in 21% of the patients with distant metastasis and in 20% of the patients without distant metastasis. Conclusion : The correlation of perineural invasion in colorectal cancer to the clinicopathologic factors such as lymph node metastasis, lymphatic invasion, vascular invasion and the stage of disease were confirmed. And perineural invasion was significantly correlated with patient’s survival. This is thought to be that perineural invasion can be a prognostic factor of colorectal cancer and it should be utilized planning adjuvant therapy for colorectal cancer patients.

Purpose: Recently, two alternatively spliced survivin variants, survivin-ΔEx3 and survivin-2B, were identified in a single copy of the survivin gene. It has been reported that the expressions of survivin splice variants significantly correlates with the clinical results in many types of human carcinoma. We investigated the transcription levels of survivin and its splice variants in human colorectal carcinomas, and analyzed correlations between survivin expression levels and clinicopathologic features. Methods: We used Western blot and real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) to analyze the protein and mRNA expression levels of survivin variants in 51 colorectal carcinomas. The quantitative RT-PCR was performed using primer pairs specific for survivin and each of its splice variants, then normalized for the gene that encodes glyceraldehydes-3-phosphate dehydrogenase. Results: In Western blotting, the protein levels of survivin were higher in the tumor tissue than in normal tissue. The expression of survivin, survivin-2B and survivin-ΔEx3 mRNA was present in 96%, 64.7%, and 82.4% of the samples, respectively. When the pathologic parameters were compared, colorectal cancers of advanced pT stages showed significant decrease in survivin-2B mRNA expression by the quantitative RT-PCR (P ＜ 0.001). Conclusion: The decreased expression of survivin-2B might be related to tumor progression in colorectal cancers. This finding indicates that alternatively spliced variants of survivin may be involved in refining the functions of survivin during tumor progression.

PURPOSE Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies. Recently, the overexpression of programmed cell death 1 (PD-1) and PD-1 ligand 1 (PD-L1) has been shown to correlate with poor prognosis in many cancers. However, the expression of PD-L1 or PD-1 ligand 2 (PD-L2) and clinical outcomes have not been fully investigated in HCC. MATERIALS AND METHODS Formalin-fixed paraffin-embedded samples were obtained from 85 patients with HCC who underwent surgery. The expression of PD-Ls (PD-L1, PD-L2) was evaluated by immunohistochemical analysis. RESULTS The proportion of high expression groups of PD-L1 and PD-L2 was 27.1% and 23.5%, respectively. Univariate analysis revealed that tumor size (p < 0.001), histological differentiation (p=0.010), PD-L1 expression (p < 0.001), and PD-L2 expression (p=0.039) were significant prognostic factors of overall survival in patients with HCC. Multivariate analysis revealed that overall tumor size (hazard ratio [HR], 4.131; 95% confidence interval [CI], 2.233 to 7.643; p < 0.001 and HR, 3.455; 95% CI, 1.967 to 6.067; p < 0.001) and PD-L1 expression (HR, 5.172; 95% CI, 2.661 to 10.054; p < 0.001 and HR, 3.730; 95% CI, 1.453 to 9.574; p=0.006) were independent prognostic values for overall and disease-free survival. Patients with high expression of PD-Ls had a significantly poorer survival than those with low expression (p < 0.001, p=0.034). CONCLUSION The overexpression of PD-Ls in HCC patients is correlated with survival and tumor recurrence. Further evaluation of PD-1 and PD-Ls as therapeutic targets and predictive biomarkers for HCC is warranted.

Colorectal cancer is one of the most common cancers and is the fourth leading cause of cancer death in Korea. Mortality of colorectal cancer is strongly associated with the metastatic spread of the disease. As such, it is important to find and characterize signaling pathways involved in colon cancer metastasis. We investigated the functional importance of RhoA using human cell lines as well as 150 colorectal cancer patient-derived samples as it remains unclear whether RhoA functions as either an oncogene or a tumor suppressor in colon cancer. RhoA was highly expressed in metastatic cancer cell lines. Although cancer cell proliferation was only moderately impaired after depletion of RhoA, RhoA-depleted cancer cells exhibited markedly reduced migration and invasion ability in vitro. Furthermore, we found that RhoA is associated with the invasion of lymph nodes and blood vessels in the patient colorectal cancer samples. Most notably, patients with higher RhoA expression had a significantly poorer 5-year survival rate after surgery. These results suggest that RhoA is a marker of poor prognosis in colorectal cancer and may be a promising target for cancer treatment.

Purpose Emerging evidence indicates that runt-related transcription factor 3 (RUNX3) is an important tumor suppressor gene in several cancer types, including colorectal cancer (CRC). However, the clinical significance of RUNX3 inactivation in CRC remains unclear. The aim of this study was to examine the correlation between clinicopathologic factors and RUNX3 hypermethylation/expression in CRC. Methods Sixty-two CRC patients who were treated at the Soonchunhyang University College of Medicine were recruited in this study. The hypermethylation of CpG islands in the RUNX3 promoter and the expression of RUNX3 mRNA were identified by methylation-specific polymerase chain reaction (PCR) and reverse transcriptase-PCR, respectively. The expression of RUNX3 was determined by immunohistochemical staining. Results Of the 62 CRC tissue samples, 20 (32.3%) presented hypermethylated RUNX3 promoters. Aberrant RUNX3 hypermethylation was found to be associated with vascular (P = 0.006) and lymphatic (P = 0.002) invasion. Hypermethylation of RUNX3 was associated with poor survival outcomes (P = 0.038). However, expression of RUNX3 was not a prognostic factor (P = 0.363). Conclusion Hypermethylation of RUNX3 may be a predictor of a poor prognosis in CRC.

Background: CPNE7, a member of copine family, is composed of calcium-dependent membrane-binding proteins. The encoded protein may play a role in calcium-mediated intracellular processes and membrane trafficking mainly. Although this protein was known as tumor suppressor in breast cancer, we identified the possibility as an oncogene in colorectal cancer. In this study, we performed to evaluate the oncogenic functions of CPNE7 in the colorectal cancer cell line and the clinical significance of CPNE7 expression in colorectal cancer patients. Method: The colorectal cancer cell lines (SW480, SW620, HCT116 and HT29) were transfected with siRNA for knockdown CPNE7. The oncogenic functions were identified in the transfected cell lines and compared them with CPNE7 highly expressing control cell lines. In vitro functional studies included cell proliferation assay, migration assay, invasion assay and semisolid agar colony forming assay. The clinical significance of CPNE7 expression was evaluated in 250 cases of colorectal cancer tissue by immunohistochemistry. Results: The knockdowned cell lines significantly showed lower oncogenic function (proliferation, migration, invasion and colony forming) compared to the CPNE7 highly expressing control cell lines (p Conclusion: This study announces that CPNE7 is a novel oncogene, an independent prognostic factor and therapeutic target in colorectal cancer. In the future, studies on in vivo assay and identifying oncogenic signal pathways of CPNE7 in colorectal cancer are necessary. Citation Format: DONGJUN JEONG, Seona Ban, Hyungjoo Kim, Seunghyun Oh, Sanghee Ji, Han Jo Kim, Sang Byung Bae, Tae Sung Ahn, Chang-Jin Kim, Moon Soo Lee, Moo-Jun Baek. Identification of novel oncogene, copine-7 (CPNE7), in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4455. doi:10.1158/1538-7445.AM2017-4455

The ability to achieve pathologic downstaging after neoadjuvant chemoradiotherapy (NCRT) is correlated with improved survival in locally advanced rectal cancer (LARC). However, there is no effective predictive markers. In this study, the expression of angiogenic markers was evaluated in pre-treatment biopsies and corresponding post-treatment resection specimens, and were correlated to histopathological tumour characteristics and response. Fifty-five patients with stage II/III rectal cancer treated with 5-fluorouracil (5-FU)-based NCRT were studied. All patients were administered NCRT followed by surgical resection. Immunohistochemical staining for angiogenic markers [hypoxia-inducible factor 1α (HIF‑1α), vascular endothelial growth factor (VEGF), stromal cell‑derived factor 1α (SDF-1α) and placental growth factor (PlGF)] was performed on specimens obtained before NCRT and after surgery. Expression of VEGF, PlGF and HIF-1α protein was downregulated after NCRT in the rectal cancer tissues (P

Two members of the Ras/Raf signaling pathway, KRAS and B-raf, are suspected to be involved in the stepwise progression of colorectal cancer (CRC) tumorigenesis. We compared the KRAS and BRAF mutation status of CRC patients with their clinicopathological characteristics and examined the effect of mutation status on survival rates. DNA was extracted from 164 samples, and the mutation statuses of KRAS and BRAF were assessed using peptide PNA clamp real-time PCR method. The presences of mutation were compared with clinicopathological factors and 5-year survival rate. Among the 164 CRC cases, KRAS mutation as detected in 71 cases (43.3 %), respectively, with no relationship with clinicopathological factors of the patients. On Kaplan–Meier survival analysis, KRAS mutation was not significantly associated with survival (p = 0.971). BRAF mutation was detected in 26 cases (15.9 %) and not associated with clinicopathological factors of the patients. However, the 5-year survival rate of BRAF mutations was significantly decreased (p = 0.02). The presence of KRAS mutation did not correlate with the various clinicopathological factors of CRC patients or the survival rate. However, the survival rate was reduced in BRAF-mutated CRC patients. Therefore, BRAF mutation could be an important prognostic factor in CRC patients.

Background Cysteine-rich 61 (Cyr61), a member of the CCN protein family, possesses diverse functionality in cellular processes such as adhesion, migration, proliferation, and survival. Cyr61 can also function as an oncogene or a tumour suppressor, depending on the origin of the cancer. Only a few studies have reported Cyr61 expression in colorectal cancer. In this study, we assessed the Cyr61 expression in 251 colorectal cancers with clinical follow up. Methods We examined Cyr61 expression in 6 colorectal cancer cell lines (HT29, Colo205, Lovo, HCT116, SW480, SW620) and 20 sets of paired normal and colorectal cancer tissues by western blot. To validate the association of Cyr61 expression with clinicopathological parameters, we assessed Cyr61 expression using tissue microarray analysis of primary colorectal cancer by immunohistochemical analysis. Results We verified that all of the cancer cell lines expressed Cyr61; 2 cell lines (HT29 and Colo205) demonstrated Cyr61 expression to a slight extent, while 4 cell lines (Lovo, HCT116, SW480, SW620) demonstrated greater Cyr61 expression than HT29 and Colo205 cell lines. Among the 20 cases of paired normal and tumour tissues, greater Cyr61 expression was observed in 16 (80%) tumour tissues than in normal tissues. Furthermore, 157 out of 251 cases (62.5%) of colorectal cancer examined in this study displayed strong Cyr61 expression. Cyr61 expression was found to be associated with pN (p = 0.018). Moreover, Cyr61 expression was associated with statistically significant cancer-specific mortality (p = 0.029). The duration of survival was significantly lesser in patients with Cyr61 high expression than in patients with Cyr61 low expression (p = 0.001). These results suggest that Cyr61 expression plays several important roles in carcinogenesis and may also be a good prognostic marker for colorectal cancer. Conclusions Our data confirmed that Cyr61 was expressed in colorectal cancers and the expression was correlated with worse prognosis of colorectal cancers.

Background: PRSS33, one of serine protease multigene family, has central roles in the regulation of a wide variety of physiological processes, including inflammation, development and malignancy. However, the function of this gene in colorectal cancer has not been elucidated. The goal of this study was to evaluate the oncogenic functions of PRSS33 in the colorectal cancer cell line and to evaluate the clinical significance of PRSS33 expression in colorectal cancer patients. Method: PRSS33 was highly expressed in colorectal cancer cell lines, HCT116, SW480 and SW620. The oncogenic functions were evaluated in the cell lines by knocking down PRSS33 with siRNA transfection and compared them with PRSS33 highly expressing control cell lines. The functional studies included cell proliferation assay, invasion assay, migration assay and anchorage-independent semisolid agar colony forming assay. The clinical significance of PRSS33 expression was evaluated in 92 cases of colorectal cancer tissue by immunohistochemistry. Results: The PRSS33 knockdowned cell lines by siRNA transfection showed significant decreases of proliferation, invasion, migration compared to those of control (p Conclusion: This study indicates that PRSS33 is a novel pro-oncogene and the expression is an independent prognostic factor in colorectal cancer patients. In the future, research on the oncogenic signal pathway of PRSS33 in colorectal cancer is necessary. Citation Format: Dongjun Jeong, Seona Ban, Hyungjoo Kim, Seunghyun Oh, Sanghee Ji, Han Jo Kim, Tae Sung Ahn, Tae Hyun Kim, Hyog Young Kwon, Seob Jeon, Sang Byung Bae, Chang-Jin Kim, Moon Soo Lee, Moo-Jun Baek. In vitro functional study of novel oncogene serine protease 33 (PRSS33) and the clinical significance of PRSS33 expression in colorectal cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 709.

Objective DEFA6 also known as human alpha defensing 6 (HD6) is a member of the alpha defensins family that defends the host against bacteria and viruses. Expression of DEFA6 is enhanced in colorectal cancer tissue and cells. The mechanism and function of DEFA6 have not been reported to play an important role in carcinogenesis and cancer progression. The goal of this study was to evaluate the protumorigenic functions of DEFA6 in the colorectal cancer cell line and to evaluate the clinical significance of DEFA6 expression in colorectal cancer patients. Methods DEFA6 was highly expressed in colorectal cancer cell lines. Colorectal cancer cell, HCT116, expressing high level of DEFA6 was used for the biological roles of DEFA6 by siRNA transfection. The protumorigenic functions of DEFA6 was evaluated by MTT assay, migration and invasion transwell assay and plate colony forming assay. DEFA6 expression was investigated by immunohistochemistry in 60 cases of colorectal cancer tissue and the association of DEFA6 expression was correlated with patient's survival. Results Immunohistochemistry analysis showed that the DEFA6 protein was expressed higher in death group (survival 5 years), (p = 0.02). The HCT116 of knockdowned DEFA6 by siRNA showed significant decrease in proliferation by MTT assay (p Conclusion DEFA6 plays important roles in invasion and migration of colorectal cancer cell according to the functional study. As patient's survival mostly depends on the migration and invasion of the tumor cells, the high expression of DEFA6 in colorectal cancer is associated with patient's survival and could be a good prognostic marker. Citation Format: Dongjun Jeong, Hyungjoo Kim, Seunghyun Oh, Seona Ban, Sanghee Ji, Han Jo Kim, Tae Sung Ahn, Tae Hyun Kim, Hyog Young Kwon, Seob Jeon, Sang Byung Bae, Chang-Jin Kim, Moon Soo Lee, Moo-Jun Baek. Defensin-alpha 6 (DEFA6) as a protumorigenic function in vitro and prognostic marker in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 708.

PURPOSE Although stromal-cell-derived factor (SDF)-1α is suggested to be involved in tumorigenicity and tumor angiogenesis, the clinicopathological significance of its expression in colorectal cancers is not fully understood. We examined SDF-1α expression in colorectal cancers and investigated its relationship to clinicopathological features such as tumor staging, lymph-node metastasis, vascular invasion (VI), lymphatic invasion (LI) and neural invasion (NI). METHODS Specimens of 83 primary colorectal cancers were examined immunohistochemically, and the relationships between clinicopathological features and SDF-1α expression were analyzed. To compare the expressions between the normal colon tissue and colorectal cancer tissues, we performed Western blot analyses. RESULTS According to the Western blot analyses, SDF-1α was more highly expressed in colorectal carcinoma tissues than in normal colonic mucosa (20/21). According to the immunohistochemical stain, SDF-1α was associated with nodal status, distant metastasis, tumor staging, VI and LI. SDF-1α expression had a significant prognostic value for overall survival. Kaplan-Meier plots of survival in patients with high SDF-1α showed that high SDF-1α expression was associated with a shorter overall survival. However, no association was found between SDF-1α expression and other pathologic or clinical variables, including age, gender, degree of differentiation, and presence of perineural invasion. CONCLUSION The expression of SDF-1α might be associated with tumor progression in colorectal cancer. Inhibition of SDF-1α could be a therapeutic option in colorectal cancer patients.

A well diversified portfolio is critical to prudent investment in a stock market. To lessen risk in a volatile market, portfolios should minimize dispersion. This paper analyzes skewness and kurtosis of businesses listed on Korean stock markets, e.g., KOSPI and KOSDAQ. It looks at distribution using the Gauss function, and examines how mean and variance can be applied in building a portfolio.

Objectives: Karyopherin alpha 2 (KPNA2) is a member of the karyopherin family that moves protein molecules into the nucleus by binding to a specific recognition sequence. It has recently been reported to play an important role in carcinogenesis and cancer progression. The aim of the present study was to elucidate the clinicopathological significance of overexpression of nuclear KPNA2 expression in colorectal cancers. Methods: KPNA2 expression was investigated by immunohistochemistry on tissue microarrays of 363 cases of colorectal cancer and the association of KPNA2 expression was examined with clinicopathologic features. Results: Thirty percent (30%) of colorectal cancers demonstrated overexpression of KPNA2. The overexpression of KPNA2 was significantly associated with high pN stages (p=0.005), vascular invasions (p Conclusion: The overexpression of KPNA2 can be a valuable poor prognostic marker of colorectal cancer and the KPNA2 can be used in therapeutic strategies. Citation Format: Moo Jun Baek, Dongjun Jeong, Tae Hyun Kim, Chang-Jin Kim, Sang Han Lee, Han Jo Kim, Sang Byeong Bae, Tae Sung Ahn. Overexpression of nuclear karyopherin alpha2 correlates with poor prognosis in patients with colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2862. doi:10.1158/1538-7445.AM2014-2862

Objectives: Angiopoietin 2 (Ang-2) is an important regulator of angiogenesis, blood vessel maturation and integrity of the vascular endothelium. The correlation between the dynamic expression of Ang-2 in tumors with regions of high angiogenic activity and a poor prognosis in many tumor types makes Ang-2 an ideal drug target. The function and mechanism of Angiopoietin 2 in colorectal cancer proliferation, invasion, metastasis and angiogenesis have not been fully elucidated to date. The aim of present study was to evaluate the biological roles of Ang-2 in the colorectal cancer cell line and to correlate the Ang-2 overexpression with the clinicopathological factors of colorectal cancers. Methods: The biological roles of Ang-2 were investigated in LoVo colorectal cancer cell line that expresses high level of Ang-2 by knockdown Ang-2 with shRNA transfection. The functional roles of Ang-2 were evaluated by invasion assay, wound healing cell migration assay, MTT assay and tube formation assay. Moreover, Ang-2 expression was investigated by immunohistochemistry on tissue microarrays of 415 cases of colorectal cancer and the association of Ang-2 expression was examined with clinicopathologic features. Results: The LoVo cell line knockdowned Ang-2 by shRNA revealed significant decreases of viability, invasion, migration and tube formation compared to that of control (p Conclusion: The overexpression of Ang-2 is significantly associated with tumor progression rather than carcinogenesis in colorectal cancer. It can be a valuable poor prognostic marker of colorectal cancer and the Ang-2 can be used in therapeutic strategies. Citation Format: Moo Jun Baek, Dongjun Jeong, Chang-Jin Kim, Tae Hyun Kim, Han Jo Kim, Tae Sung Ahn, Sang Byung Bae, Sang Han Lee. In vitro functional study of Ang 2 in colorectal cancer cell line and the significance of Ang 2 expression in colorectal cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 33. doi:10.1158/1538-7445.AM2014-33