Biomedical subjects

Koshi Mimori

Publications and source records attributed to Koshi Mimori.

At least 19 recordsLinked to original sources

PubMed2006

Opa interacting protein 5 (OIP5) is a novel cancer-testis specific gene in gastric cancer.

BACKGROUND: Identification of novel cancer-specific antigens is important for the advancement of immunotherapy. Our aim was to identify cancer-specific genes in gastric cancer. METHODS: Using cDNA microarray analysis, we detected genes overexpressed specifically in gastric cancer cells. The expression levels of selected genes, including OIP5, was confirmed by real time RT-PCR analysis in tumor/normal paired bulk samples of 58 clinical cases. The expression levels of selected genes in normal tissues were also determined with a human total RNA master panel. We also compared the expression status of OIP5 with that of the other known cancer-testis specific genes. RESULTS: Twenty-two genes were determined to be upregulated in gastric cancer cells. Among these, three genes (CDC6, Exo1, and OIP5) were selected and confirmed to be upregulated in the tumor tissue compared to normal tissue. A human total RNA master panel demonstrated that OIP5, but not Exo1 or CDC6, showed high specificity in testis. Thus OIP5 may be considered a cancer-testis specific gene. In 58 clinical cases of gastric cancer examined, we found OIP5 gene expression in 27 cases (47%). Thirteen of these 27 cases showed no expression of the known cancer specific genes such as MAGE-1, MAGE-3 or NY-ESO-1. CONCLUSIONS: Using a combination of LMD and microarray, we identified OIP5 as a cancer-testis specific gene. Further expression analysis in a set of clinical cases revealed that OIP5 may be a novel immunotherapy target for patients with gastric cancer.

Adenocarcinoma↗

PubMed2006

Loss of MAL expression in precancerous lesions of the esophagus.

BACKGROUND: We have identified a novel function of MAL (T-cell differentiation-related gene) as a candidate suppressor gene in esophageal cancer. As the role of MAL expression in esophageal carcinogenesis is as yet undetermined, MAL expression in a rat multi-step carcinogenic model and in precancerous lesions of the human esophagus was investigated. Microarray analysis between MAL-transfectant and control cells was also carried out to clarify how MAL confers its anti-tumor effects. MATERIALS AND METHODS: (1) In the rat model, MAL expression levels in laser microdissected normal esophageal epithelium, dysplastic tissues and carcinoma tissues were examined by reverse transcription (RT)-PCR. (2) Immunostaining with MAL antibody was performed in 10 dysplastic lesions adjacent to cancer in six cases of esophageal cancer. (3) We established a MAL transfectant using a Tet-off vector in esophageal cancer cells and performed microarray analysis under MAL-positive and MAL-negative conditions. RESULTS: (1) In the rat model, MAL mRNA expression was observed only in the normal samples. (2) MAL expression was observed distinctively in differentiated or keratinized normal tissues and was not observed in either dysplastic lesions or carcinoma tissue. (3) Up-regulated genes in MAL-positive cells included keratin 18 (transfectant/control = 2.94) and keratin 10 (t/c = 2.82). CONCLUSION: MAL expression was lost in dysplastic lesions of the rat carcinoma model as well as the human esophagus. The up-regulated keratins revealed by microarray analysis and the strong staining of the differentiated normal tissues in immunohistochemical study support the role of MAL as a regulator of differentiation in esophageal epithelium.

Animals↗

PubMed2006

Fhit modulates the DNA damage checkpoint response.

In preneoplastic lesions, the DNA damage checkpoint is induced and loss of heterozygosity at the FRA3B/FHIT common chromosome fragile region precedes or is coincident with activation of the checkpoint response in these early stages. Introduction of exogenous Fhit into cells in vitro led to modulation of expression of checkpoint proteins Hus1 and Chk1 at mid-S checkpoint, a modulation that led to induction of apoptosis in esophageal cancer cells but not in noncancerous primary cultures. Mutation of the conserved Fhit tyrosine 114 resulted in failure of this function, confirming the importance of this residue. The results suggest that the DNA damage-susceptible FRA3B/FHIT chromosome fragile region, paradoxically, encodes a protein that is necessary for protecting cells from accumulation of DNA damage through its role in modulation of checkpoint proteins, and inactivation of Fhit contributes to accumulation of abnormal checkpoint phenotypes in cancer development.

Acid Anhydride Hydrolases↗

PubMed2006

Fatty acid binding protein 6 is overexpressed in colorectal cancer.

PURPOSE: Fatty acid binding protein 6 (FABP6) is a cancer-related protein that acts as an intracellular transporter of bile acid in the ileal epithelium. Because bile acids are implicated in the carcinogenesis of colorectal cancer, we evaluated FABP6 expression in colorectal cancer. EXPERIMENTAL DESIGN: The expression of FABP6 mRNA was evaluated in 78 paired samples of cancer/normal tissue representing colorectal cancer cases, plus 16 adenomas, and 16 metastatic lymph nodes. An immunohistochemical study was conducted with paraffin sections. In vitro transfection was done to determine FABP6's biological roles. RESULTS: The expression of FABP6 mRNA was significantly higher in cancer (75 of 78, 96.2%) than in normal tissue (P<0.001). The expression of mRNA was increased in cancer compared with adenoma, but was dramatically decreased in node metastases. Tumors with high FABP6 expression were smaller in size (P<0.01), more often in the left colon (P<0.05), and had shallower invasion into the bowel wall (P<0.05) compared with those with low expression. There was no significant difference between high- and low-expression tumors regarding clinicopathologic variables such as histologic type, lymph node, or liver metastasis, Dukes' classification, and prognosis. Immunohistochemical study revealed that FABP6 expression was primarily observed in cancer cells. In vitro transfection revealed that transfectants showed weaker invasiveness (P<0.05), more dominant proliferation (P<0.001), and less apoptosis than mock cells. CONCLUSIONS: The expression of FABP6 was higher in primary colorectal cancers and adenomas than in normal epithelium, but was dramatically decreased in lymph node metastases, suggesting that FABP6 may play an important role in early carcinogenesis.

Adenoma↗

PubMed2006

Clinical significance of TROP2 expression in colorectal cancer.

PURPOSE AND EXPERIMENTAL DESIGN: To identify cancer-related genes, the expression profiles of colorectal cancer cells and normal epithelial cells were examined and compared using laser microdissection and cDNA microarray analysis. From these combined techniques, several cancer-related genes, including TROP2, were identified. TROP2 is known as a calcium signal transducer and is highly expressed in several types of tumors. However, no studies have investigated the significance of TROP2 expression in colorectal cancer. Thus, the expression status of TROP2 was investigated in 74 colorectal cancer samples by quantitative real-time reverse transcription-PCR and immunohistochemical studies. RESULTS: Laser microdissection and cDNA microarray analysis showed that there were 84 overexpressed genes in cancer cells. One of the highly overexpressed genes was TROP2. Quantitative real-time reverse transcription-PCR showed that TROP2 expression in cancer samples was significantly higher than in normal samples (P < 0.001). The samples were divided into high (n = 26) and low (n = 48) TROP2 expression groups. The cases with high TROP2 expression showed a higher frequency of liver metastasis (P = 0.005) and more cancer-related death (P = 0.046). Those cases also had an inclination of deeper depth of invasion (P = 0.064) and more lymph node metastasis (P = 0.125). Interestingly, the patients with high TROP2 expression tumors had poorer prognosis (P = 0.0036). Multivariate analysis showed that TROP2 expression status was an independent prognostic factor (relative risk, 2.38; 95% confidence interval, 1.29-4.74; P < 0.01). CONCLUSION: TROP2 is one of the cancer-related genes that correlates with biological aggressiveness and poor prognosis of colorectal cancer. Thus, TROP2 is a possible candidate gene for diagnosis and molecular target therapy of colorectal cancer.

Aged↗

PubMed2006

FHIT is up-regulated by inflammatory stimuli and inhibits prostaglandin E2-mediated cancer progression.

The FHIT gene is known to be susceptible to environmental carcinogens. Formation of prostaglandin E(2) (PGE(2)) is catalyzed by cyclooxygenase-2 (COX-2) and may influence malignant phenotype in colorectal cancer. We explored whether FHIT might play a role in progression of colorectal cancer through inflammation-associated PGE(2) activity. Immunohistochemical study of COX-2 and FHIT expression was done in 92 colorectal cancer tumors. We also used a FHIT-expressing cancer cell line (H460) induced by ponasterone A and two FHIT small interfering RNA-treated colorectal cancer cell lines (CCK81 and DLD1). After PGE(2) stimulation, we compared synthesis of PGE(2) (ELISA assay) and cell proliferation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay]. Immunohistochemistry showed a significant association between COX-2 and FHIT expression in colorectal cancers (P < 0.01). In a subset of 41 COX-2-expressing tumors, 12 FHIT(-) tumors showed deeper cancer invasion than 29 FHIT(+) tumors (P < 0.01). Experimental study, however, showed there was no direct interaction between FHIT and COX-2. Considered with results from another experiment with epidermal growth factor receptor (EGFR), we hypothesize that FHIT and COX-2 might be regulated by a common molecule, such as EGFR. Additionally, there was an inverse and direct correlation between PGE(2) synthesis and FHIT in vitro, suggesting that FHIT's postulated antiaggressive effect on tumor goes through PGE(2) but not COX-2. Loss of FHIT expression in colorectal cancer suggests higher malignant potential. We conclude that FHIT suppressed cancer cell proliferation in this malignancy by directly inhibiting synthesis of PGE(2) but not affecting that of COX-2.

Acid Anhydride Hydrolases↗

PubMed2006

The epidermal growth factor receptor gene sequence is highly conserved in primary gastric cancers.

BACKGROUND AND OBJECTIVES: Recent studies have disclosed the presence of somatic mutations in the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancers (NSCLC), and susceptibility to the EGFR tyrosine kinase inhibitor (gefitinib) was determined by the presence of mutations in the kinase domain of this gene. We thus predicted a clinical benefit of gefitinib against the 12% of primary colorectal cancers exhibiting a mutation reflective of this potential distinctive susceptibility. PATIENTS AND METHODS: The mutation status of the kinase domain in EGFR in different primary cancers has important clinical consequences, because the presence of a mutation is recognized as a reliable indicator for the effectiveness of gefitinib administration. In the current study, we investigated the presence of somatic mutations in exons 18-21 coding the ATP-binding domain in five gastric cancer cell lines and 39 primary gastric cancers and their corresponding normal tissues. RESULTS AND CONCLUSIONS: The kinase domain of EGFR is highly conserved in whole gastric cancer cell lines and cases, therefore treatment with gefitinib is unfortunately not recommended for such malignancy.

Adult↗

PubMed2006

Cancer stem cells in human gastrointestinal cancers.

The concept of cancer stem cell has developed in leukemia. Recently, it has expanded to include solid tumors such as brain or breast tumors. However, the descriptions are not recognized in human gastrointestinal cancers. We used flow cytometry and the DNA-binding dye (Hoechst 33342) to isolate side population (SP) cells from various human gastrointestinal system cancer cell lines. The SP cell fraction is considered to contain abundant stem cells. Fifteen of 16 cancer cell lines from the gastrointestinal system contained 0.3-2.2% SP cells. We studied the characteristics of the SP cells in hepatic or colon cancer cell lines. The results demonstrated that cancers of the gastrointestinal system do contain SP cells that show some characters of so-called stem cells. In this paper, we report our study results with a review of the literature.

ATP-Binding Cassette Transporters↗

PubMed2006

Usefulness and clinical significance of quantitative real-time RT-PCR to detect isolated tumor cells in the peripheral blood and tumor drainage blood of patients with colorectal cancer.

The clinical significance of isolated tumor cells (ITC) circulating in the blood of patients with colorectal cancer is unclear. In this study, we investigated the relationship between the presence of ITC that express carcinoembryonic antigen (CEA) and/or cytokeratin 20 (CK20) transcripts in the blood and the clinicopathological findings and prognosis using the quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay. We studied peripheral blood and tumor drainage blood from 167 patients with colorectal cancer. Quantitative real-time RT-PCR assay was able to detect one tumor cell in 3x10(6) peripheral blood mononuclear cells. Applying a cut-off value, CEA and/or CK20 (CEA/CK20) were detected in 10.2% (17/167) of the patients' preoperative peripheral blood samples and 34.1% (57/167) of the patients' tumor drainage blood samples. In the relationship between the CEA/CK20 of the blood and the clinicopathological factors, a significant correlation was demonstrated between the positivity of marker genes and the depth of invasion, venous invasion, lymph node metastasis, liver metastasis or stage. The disease-free and overall survival of patients with CEA/CK20-positive peripheral or tumor drainage blood was significantly shorter than that of marker gene-negative patients. CEA/CK20 transcripts in tumor drainage blood were independent factors for prognosis in disease-free survival and overall survival. These results suggest that detecting CEA/CK20 mRNA in tumor drainage blood by real-time RT-PCR has prognostic value in patients with colorectal cancer. Large scale and long-term clinical studies are needed to confirm the prognostic value of genetically detecting ITC in the peripheral blood.

Adult↗

PubMed2006

Differential gene expression profiles of radioresistant pancreatic cancer cell lines established by fractionated irradiation.

Identification of the genes that are differentially-expressed between radiosensitive and radioresistant cancer cells is important to the ability to predict the clinical effectiveness of radiotherapy. We established radioresistant human pancreatic cancer cell lines using fractionated irradiation in order to identify genes that are differentially-expressed between parental lines and radioresistant cell sublines. Six pancreatic cancer cell lines (PK-1, PK-8, PK-9, T3M4, MiaPaCa2 and PANC-1) were treated with 10 Gy fractionated irradiation at approximately two-week intervals (total dose 150-180 Gy). Five radioresistant sublines (PK-1, PK-8, PK-9, T3M4, and MiaPaCa2) were successfully established. Using oligonucleotide microarrays containing 17,086 genes, we identified 73 up-regulated genes and 55 down-regulated genes common to radioresistant sublines. Subsequent analysis by quantitative RT-PCR confirmed the reliability of our microarray strategy. Up-regulated genes were associated with growth factor (example, amphiregulin), cell-cycle check point (MAPKAPK2), intracellular signaling pathway (regucalcin), and angiogenesis stimulation (angiopoietin 2). Down-regulated genes were associated with apoptosis (caspase 8), retinoid esterification (lecithin retinol acyltransferase), and electron transport (calcium-activated chloride channel 1). Some of these genes have known association with response to radiation, such as caspase 8 and MAPKAPK2, but others are novel. Global gene analysis of radioresistant sublines may provide new insights into the mechanisms underlying clinical radioresistance and to improving the efficacy of radiotherapy for pancreatic cancer.

Apoptosis↗

PubMed2006

[Occult micrometastasis].

The concept of occult micrometastasis has been recognized for several decades. Recently, the balance of evidence favours the hypothesis that micrometastatic cells impacts on survival in spite of few clinical large-scale trials. Immunocytochemistry using anti-cytokeratin monoclonal antibodies is often used to detect micrometastatic cells. The strategy for detection of micrometastasis would help in the design of "tailor-made treatment". Furthermore, the genomic analyses of micrometastatic cells will contribute to the development of more effective strategies to treat cancer patients as well as the clarification of the carcinogenesis and the mechanism of clinical metastasis which is the leading cause of cancer-related death.

Biomarkers, Tumor↗

PubMed2006

Gene expression profiling of lymph node metastasis by oligomicroarray analysis using laser microdissection in esophageal squamous cell carcinoma.

We applied oligomicroarray analysis of 17086 genes to identify the genes related to lymph node metastasis in esophageal squamous cell carcinoma (ESCC). The samples of cancer and non-cancerous paired tissue were taken from 16 patients with ESCC who underwent esophagectomy with lymph node dissection. Total ribonucleic acid was extracted from the cancer cells obtained by using laser microdissection and was amplified by T7 based-amplification for the application to the oligomicroarray. The oligomicroarray demonstrated 43 overexpressed genes, such as cell-cycle regulators, cell adhesion related genes, anti-apoptosis related genes, and 138 suppressed genes such as cell differentiation related and apoptosis related genes in ESCC cells with lymph node metastasis. Among them, 5 overexpressed genes (SPP-1, CKS2, CCT5, STMN1, NDUFB9) and one suppressed expression gene (GJB2) were selected in the gene profiles, and then the expressions of those genes were confirmed by real-time semi-quantitative reverse transcriptional polymerase chain reaction (RT-PCR) method for confirmation of the result not only in study cases but also in additional 21 cases. The gene expression by real-time semi-quantitative RT-PCR was in accordance with the microarray data. Although we were able to extract some genes related to nodal metastasis in ESCC, further examination is necessary in other genes as well as the interaction of stromal tissues.

Aged↗

PubMed2005

Characterization of a side population of cancer cells from human gastrointestinal system.

A subset of stem cells, termed "side population" (SP) cells, has been identified and characterized in several mammalian tissues and cell lines. However, SP cells have never been identified or isolated from gastrointestinal cancers. We used flow cytometry and the DNA-binding dye Hoechst 33342 to isolate SP cells from various human gastrointestinal system cancer cell lines. Fifteen of sixteen cancer cell lines from the gastrointestinal system contained 0.3%-2.2% SP cells. Next, we used an oligonucleotide microarray to analyze differentially expressed genes between SP and non-SP cells of hepatoma HuH7. The expression of GATA6, which is associated with embryonic development and hepatocytic differentiation, was significantly upregulated in HuH7 SP cells. The expression of ABCG2, ABCB1, and CEACAM6, which are associated with chemoresistance, was also significantly increased in SP cells. In addition, some epithelial markers and mesenchymal markers were overexpressed in SP cells. Reverse transcription-polymerase chain reaction and immunocytochemical staining validated these results and suggested a multilineage potential for HuH7 SP cells. In hepatoma HuH7 and colorectal SW480 cell lines, SP cells showed evidence for self-renewal, generating both SP and non-SP cells. Finally, chemoresistance to anticancer agents, including doxorubicin, 5-fluorouracil, and gemcitabine, were compared between HuH7 SP and non-SP cells using an ATP bioluminescence assay. The HuH7 SP cells expressed a higher resistance to doxorubicin, 5-fluorouracil, and gemcitabine compared with non-SP cells. These findings demonstrate that cancers of the gastrointestinal system do contain SP cells that show some characteristics of so-called stem cells.

Antigens, Differentiation↗

PubMed2005

Clinicopathologic and biological significance of kallikrein 6 overexpression in human gastric cancer.

PURPOSE: Human kallikrein genes (KLK) have been reported to be involved in human malignancies and several KLKs are promising biomarkers of prostate, ovarian, testicular, and breast cancers. Herein, we investigated the clinicopathologic and biological significance of KLK6 gene expression in human gastric cancer. PATIENTS AND METHODS: Using real-time reverse transcription-PCR, we analyzed the KLK6 expression status with respect to various clinicopathologic variables in 66 patients with gastric cancer. In addition, we established a KLK6 stably suppressed gastric cancer cell line (MKN28) using small interfering RNA-mediated gene silencing, and investigated its effects on the cell proliferation rate, cell cycle, and invasiveness. RESULTS: The KLK6 gene expression in cancerous tissue (0.37 +/- 0.53) was significantly (P < 0.000001) higher than that in noncancerous tissue (0.026 +/- 0.060). Elevated KLK6 expression was significantly associated with lymphatic invasion (P = 0.03). Furthermore, patients with a high KLK6 expression had a significantly poorer survival rate than those with a low KLK6 expression (P = 0.03). Therefore, we showed that KLK6 gene silencing with KLK6 small interfering RNA effectively suppressed the cell proliferation rate (P = 0.002), cell population in the S phase (P < 0.01), and invasiveness (P < 0.01) in comparison to mock-transfected cells. CONCLUSIONS: The KLK6 gene is markedly overexpressed in gastric cancer tissue and its expression status may be a powerful prognostic indicator for patients with gastric cancer. Our findings also suggest that KLK6 may possibly be a novel target for gastric cancer therapy by gene-silencing procedures.

Biomarkers, Tumor↗

PubMed2005

Clinicopathologic and prognostic values of apolipoprotein D alterations in hepatocellular carcinoma.

We previously identified apolipoprotein D (Apo D) as a novel tumor suppressor gene based on the pharmacological unmasking of epigenetic silencing. We analyzed Apo D expression using real-time reverse transcription-PCR and evaluated its expression status based on the clinicopathological parameters of 70 patients with hepatocellular carcinoma (HCC). Immunohistochemical staining was also performed. We determined the methylation status of Apo D gene promoter by methylation-specific PCR (MSP). The Apo D gene-expression in tumor tissue was significantly lower than that in nontumor tissue (p = 0.011). A low Apo D expression significantly correlated with less-differentiated HCC (p = 0.019). Immunohistochemical studies confirmed a decreased Apo D expression in poorly differentiated tumors. The prognosis of patients with a lower Apo D gene-expression was significantly worse than that in those with a higher expression (p = 0.028). The Apo D gene-expression was an independent prognostic factor (relative risk: 2.36, p = 0.018). An MSP assay showed a low-level of methylation in well differentiated HCC and a high-level of methylation in less differentiated tumors. Apo D may be a novel tumor suppressor gene of HCC, and its expression status may be a useful biomarker for predicting the patient outcome.

Aged↗

PubMed2005

Frag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis.

We report the identification and characterization of a potent regulator of genomic integrity, mouse and human FRAG1 gene, a conserved homolog of replication factor C large subunit that is homologous to the alternative replication factor C subunits Elg1, Ctf18/Chl12, and Rad24 of budding yeast. FRAG1 was identified in a search for key caretaker genes involved in the regulation of genomic stability under conditions of replicative stress. In response to stress, Atr participates in the down-regulation of FRAG1 expression, leading to the induction of apoptosis through the release of Rad9 from damaged chromatin during the S phase of the cell cycle, allowing Rad9-Bcl2 association and induction of proapoptotic Bax protein. We propose that the Frag1 signal pathway, by linking replication stress surveillance with apoptosis induction, plays a central role in determining whether DNA damage is compatible with cell survival or whether it requires cell elimination by apoptosis.

Amino Acid Sequence↗

PubMed2005

PGP9.5 promoter methylation is an independent prognostic factor for esophageal squamous cell carcinoma.

PGP9.5/UCHL1 is a member of the carboxyl-terminal ubiquitin hydrolase family with a potential role in carcinogenesis. We previously identified PGP9.5 as a putative tumor-suppressor gene and methylation of the promoter as a cancer-specific event in primary cancer tissues. In this current study, we analyzed PGP9.5 methylation in 50 esophageal squamous cell carcinoma (ESCC) primary tumors with well characterized clinicopathologic variables including patient outcome. Two independent modalities for methylation analysis (TaqMan methylation-specific PCR and combined bisulfite restriction analysis) were used to analyze these samples. The two data sets were consistent with each other, as the 21 patients (42%) with highest methylation levels by TaqMan analysis all showed visible combined bisulfite restriction analysis bands on acrylamide gels. Using an optimized cutoff value by TaqMan quantitation, we found that patients with higher PGP9.5 methylation ratios in the primary tumor showed poorer 5-year survival rates than those without PGP9.5 methylation (P = 0.01). A significant correlation was also seen between PGP9.5 promoter methylation and the presence of regional lymph node metastases (P = 0.03). Multivariate analysis subsequently revealed that PGP9.5 methylation was an independent prognostic factor for ESCC survival (P = 0.03). These results suggest that PGP9.5 promoter methylation could be a clinically applicable marker for ESCC progression.

Carcinoma, Squamous Cell↗

PubMed2005

Clinical significance of human kallikrein gene 6 messenger RNA expression in colorectal cancer.

PURPOSE: Human kallikrein gene 6 (KLK6) is a member of the human kallikrein gene family, and recent studies have found that many kallikreins have altered expression patterns in various malignancies. The purpose of the current study was to quantify the expression of KLK6 in malignant and benign colorectal tissues and to statistically analyze whether KLK6 expression levels correlate with clinicopathologic variables and prognosis in patients with colorectal cancer. EXPERIMENTAL DESIGNS: Paired colorectal tissue samples from cancerous and corresponding noncancerous tissues were obtained from 63 patients with colorectal cancer who underwent surgical resection. Quantitative analyses of KLK6 mRNA expression were done using real-time quantitative reverse transcription-PCR. RESULTS: KLK6 mRNA overexpression in cancerous tissues compared with normal counterparts was observed in 57 of 63 (90%) patients. The mean expression level of KLK6 mRNA in cancerous tissues was significantly higher than that in noncancerous tissues (P < 0.0001). Elevated KLK6 expression was significantly correlated with serosal invasion (P < 0.05), liver metastasis (P < 0.05), and advanced Duke's stage (P < 0.01). Furthermore, patients with high KLK6 expression had a significantly poorer actuarial overall survival than patients with low KLK6 expression (5-year overall survival rates: 54% and 73%, respectively, P < 0.05). CONCLUSIONS: The results of this study indicated that KLK6 mRNA expression was significantly higher in cancerous than in noncancerous colorectal tissues, and high expression of KLK6 mRNA correlated with serosal invasion, liver metastasis, advanced Duke's stage, and a poor prognosis for patients with colorectal cancer.

Aged↗