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1.
World J Gastroenterol ; 26(3): 307-323, 2020 Jan 21.
Article in English | MEDLINE | ID: mdl-31988591

ABSTRACT

BACKGROUND: Single nucleotide polymorphisms (SNPs) are universally present in nucleotide excision repair (NER) pathway genes, which could make impacts on colorectal carcinogenesis and prognosis. AIM: To explore the association of all tagSNPs in NER pathway genes with colorectal cancer (CRC) risk and prognosis in a northern Chinese population by a two-stage case-control design composed of a discovery and validation stage. METHODS: Genotyping for NER SNPs was performed using kompetitive allele specific PCR. In the discovery stage, 39 tagSNPs in eight genes were genotyped in 368 subjects, including 184 CRC cases and 184 individual-matched controls. In the validation stage, 13 SNPs in six genes were analyzed in a total of 1712 subjects, including 854 CRC cases and 858 CRC-free controls. RESULTS: Two SNPs (XPA rs10817938 and XPC rs2607775) were associated with an increased CRC risk in overall and stratification analyses. Significant cumulative and interaction effects were also demonstrated in the studied SNPs on CRC risk. Another two SNPs (ERCC2 rs1052555 and ERCC5 rs2228959) were newly found to be associated with a poor overall survival of CRC patients. CONCLUSION: Our findings suggest novel SNPs in NER pathway genes that can be predictive for CRC risk and prognosis in a large-scale Chinese population. The present study has referential values for the identification of all-round NER-based genetic biomarkers in predicting the susceptibility and clinical outcome of CRC.


Subject(s)
Colorectal Neoplasms/genetics , DNA Repair/genetics , Genetic Predisposition to Disease/genetics , Signal Transduction/genetics , Asian People/genetics , Carcinogenesis/genetics , Case-Control Studies , Colorectal Neoplasms/mortality , DNA-Binding Proteins/genetics , Endonucleases/genetics , Female , Genetic Markers/genetics , Genotype , Humans , Male , Middle Aged , Nuclear Proteins/genetics , Polymorphism, Single Nucleotide , Prognosis , Risk Factors , Transcription Factors/genetics , Xeroderma Pigmentosum Group D Protein/genetics
2.
Support Care Cancer ; 28(6): 2911-2919, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31758321

ABSTRACT

PURPOSE: Sleep disturbances are common in cancer patients, but little is known about preoperative insomnia and its associated factors in colorectal cancer (CRC) patients. The aim of this study was to clarify the relationship between preoperative insomnia and its associated factors (i.e., pain, anxiety, self-esteem, and coping styles) in CRC patients. METHODS: A cross-sectional study was conducted in consecutive CRC inpatients (N = 434), who were required to complete the questionnaires about insomnia, pain, anxiety, self-esteem, and coping styles (acceptance/resignation, confrontation, avoidance) before the day of surgery. Hierarchical regression analyses were conducted to explore the relationships between preoperative anxiety and its associated factors. RESULTS: Based on the cutoff value of Athens Insomnia Scale (scores ≥ 6) in Chinese cancer patients, the prevalence of insomnia was 38.2% before surgery. Pain (ß = 0.087, p = 0.015) and anxiety (ß = 0.372, p < 0.001) were positively associated with preoperative insomnia, while self-esteem (ß = - 0.479, p < 0.001) and confrontation coping (ß = - 0.124, p = 0.003) showed protective effects on preoperative insomnia when putting them together into hierarchical regression. The associated factors together accounted for an additional variance of preoperative insomnia (47.6%). CONCLUSIONS: In line with previous findings, the detrimental effects of pain and anxiety on preoperative insomnia were also observed in our study. More importantly, our main new findings were that self-esteem and confrontation coping played important roles in alleviating preoperative insomnia among CRC patients. Clinicians should take these results into account when developing cancer care management to relieve preoperative insomnia.


Subject(s)
Anxiety/epidemiology , Cancer Pain/epidemiology , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/psychology , Colorectal Neoplasms/surgery , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep Initiation and Maintenance Disorders/psychology , Adaptation, Psychological/physiology , Adult , Aged , Aged, 80 and over , Anxiety/complications , Anxiety/psychology , Asian People/statistics & numerical data , Cancer Pain/psychology , Cancer Pain/surgery , China/epidemiology , Colorectal Neoplasms/complications , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Preoperative Period , Prevalence , Sleep Initiation and Maintenance Disorders/diagnosis , Surveys and Questionnaires
3.
J Cancer ; 10(10): 2229-2236, 2019.
Article in English | MEDLINE | ID: mdl-31258726

ABSTRACT

Purpose: The study was conducted to investigate the relationship of serum pepsinogens PGI, PGII, gastrin-17, and Hp-IgG with colorectal cancer (CRC), aiming to explore the clinical significance of serum markers reflecting gastric function and H. pylori infection in CRC. Methods: A total of 569 CRC cases and 569 age and sex-matched controls were enrolled in this study between June 2012 and April 2016 from The First Hospital of China Medical University. The serum markers reflecting gastric function and H. pylori infection were detected using ELISA, including PGI, PGII, PGI/II ratio, G-17 and Hp-IgG. Information of clinicopathological parameters and tumor biomarkers was collected from the medical records of inpatients, including CEA, CA199, CA125, CA153 and AFP. Results: Serum PGII, G-17 levels and Hp-IgG were increased in CRC, while PGI and PGI/II ratio appeared no significant difference between CRC and controls. In subgroup analysis, PGII was more significant in males (P=0.014). Hp-IgG was demonstrated higher in age<60y (P=0.001). With respect to the association with serum tumor biomarkers, G-17 level was associated with the rise of CA125 (P=0.005, OR (95%CI): 4.89 (1.90-12.57)), Hp-IgG increasing was associated with the rise of CA125 (P=0.024, OR (95%CI): 4.10 (1.54-10.93)). Conclusions: Serum PGII, G-17 and Hp-IgG were associated with CRC risk. The serum levels of G-17 and Hp-IgG were associated with the rise of CA125 in patients with CRC.

4.
PLoS One ; 10(8): e0136447, 2015.
Article in English | MEDLINE | ID: mdl-26317520

ABSTRACT

BACKGROUND: The phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays a critical role in angiogenesis and cell growth, proliferation, metabolism, migration, differentiation, and apoptosis. Genetic diversity in key factors of this pathway may influence protein function and signal transduction, contributing to disease initiation and progression. Studies suggest that MTOR rs1064261 and AKT rs1130233 polymorphisms are associated with risk and/or prognosis of multiple cancer types. However, this relationship with gastric cancer (GC) remains unclear. The aim of this study was to investigate the role of MTOR and AKT polymorphisms in the risk and prognosis of GC. METHODS: The Sequenom MassARRAY platform was used to genotype 1842 individuals for MTOR rs1064261 T→C and AKT rs1130233 G→A polymorphisms. ELISA was used to detect Helicobacter pylori antibodies in serum. Immunohistochemical analysis was used to detect total and phosphorylated MTOR and AKT proteins. RESULTS: The MTOR rs1064261 (TC+CC) genotype and the AKT rs1130233 (GA+AA) genotype were associated with increased risk of GC in men (P = 0.049, P = 0.030). In H. pylori-negative individuals, the AKT rs1130233 GA and (GA+AA) genotypes were related to increased risk of atrophic gastritis (AG; P = 0.012, P = 0.024). Notably, the AKT rs1130233 (GA+AA) genotype demonstrated significant interactions with H. pylori in disease progression from healthy controls (CON) to AG (P = 0.013) and from AG to GC (P = 0.049). Additionally, for individuals with the AKT rs1130233 variant, those in the H. pylori-positive group had higher levels of phosphorylated AKT (p-AKT) expression. The AKT rs1130233 genotype was found to be associated with clinicopathological parameters including lymph node metastasis and alcohol drinking (P<0.05). CONCLUSION: MTOR rs1064261and AKT rs1130233 polymorphisms were associated with increased GC risk in males and increased AG risk in H. pylori-negative individuals. A significant interaction existed between the AKT rs1130233 genotype and H. pylori infection in CON→AG→GC disease progression. The AKT rs1130233 genotype influenced p-AKT protein expression in H. pylori-infected individuals.


Subject(s)
Gastritis, Atrophic/genetics , Polymorphism, Single Nucleotide , Proto-Oncogene Proteins c-akt/genetics , Stomach Neoplasms/genetics , TOR Serine-Threonine Kinases/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Male , Middle Aged
5.
Asian Pac J Cancer Prev ; 15(18): 7639-44, 2014.
Article in English | MEDLINE | ID: mdl-25292041

ABSTRACT

BACKGROUND: RESULTS from previous studies concerning the association of ERCC4 rs1800067 polymorphism with risk of cancer were inconsistent. To explore the exact relation with susceptibility, we conducted the present meta-analysis. MATERIALS AND METHODS: Literature of electronic databases including PubMed, Web of Science, EMBASE, Wanfang and Chinese National Knowledge Infrastructure (CNKI) were systematically searched. ORs and their 95%CIs were used to assess the strength of associations between ERCC4 polymorphism and cancer risk. RESULTS: There was no significant association between ERCC4 rs1800067 AA or AG genotypes and overall risk of cancer (AA vs. GG: OR=0.998, 95%CI=0.670-1.486, P=0.992; AG vs. GG: OR=0.970, 95%CI=0.888- 1.061, P=0.508). A dominant genetic model also did not demonstrate significant association of (AA+AG) genotype carriers with altered risk of overall cancer (OR=0.985, 95%CI=0.909-1.068, P=0.719). In addition, no significant association was observed between A allele of ERCC4 rs1800067 A/G polymorphism and altered cancer risk compared with G allele (OR=0.952, 95%CI=0.851-1.063, P=0.381). Subgroup analysis suggested that AA genotype carriers were significantly associated with decreased risk of glioma compared with wild-type GG genotype individuals (OR=0.523, 95%CI=0.275-0.993, P=0.048). For subgroup of lung cancer, A allele of ERCC4 rs1800067 A/G polymorphism was significantly associated with decreased risk of lung cancer compared with G allele (OR=0.806, 95%CI=0.697-0.931, P=0.003). CONCLUSIONS: This meta-analysis indicated that ERCC4 rs1800067 A/G polymorphism might not be associated with risk of overall cancer. However, individuals with the AA genotype were associated with significantly reduced risk of glioma compared with wild-type GG genotype; The A allele was associated with significantly reduced risk of lung cancer compared with G allele. Future large- scale studies performed in multiple populations are warranted to confirm our results.


Subject(s)
DNA-Binding Proteins/genetics , Genetic Predisposition to Disease , Neoplasms/genetics , Polymorphism, Genetic/genetics , Case-Control Studies , Humans , Prognosis , Risk Factors
6.
PLoS One ; 9(2): e89203, 2014.
Article in English | MEDLINE | ID: mdl-24586594

ABSTRACT

BACKGROUND: The aim of this study was to investigate the interaction effects of pri-let-7a-1 rs10739971 with pepsinogen C (PGC) and excision repair cross complementing group 6 (ERCC6) gene polymorphisms and its association with the risks of gastric cancer and atrophic gastritis. We hoped to identify miRNA polymorphism or a combination of several polymorphisms that could serve as biomarkers for predicting the risk of gastric cancer and its precancerous diseases. METHODS: Sequenom MassARRAY platform method was used to detect polymorphisms of pri-let-7a-1 rs10739971 G → A, PGC rs4711690 C → G, PGC rs6458238 G → A, PGC rs9471643 G → C, and ERCC6 rs1917799 in 471 gastric cancer patients, 645 atrophic gastritis patients and 717 controls. RESULTS: An interaction effect of pri-let-7a-1 rs10739971 polymorphism with ERCC6 rs1917799 polymorphism was observed for the risk of gastric cancer (P interaction = 0.026); and interaction effects of pri-let-7a-1 rs10739971 polymorphism with PGC rs6458238 polymorphism (P interaction = 0.012) and PGC rs9471643 polymorphism (P interaction = 0.039) were observed for the risk of atrophic gastritis. CONCLUSION: The combination of pri-let-7a-1 rs10739971 polymorphism and ERCC6 and PGC polymorphisms could provide a greater prediction potential than a single polymorphism on its own. Large-scale studies and molecular mechanism research are needed to confirm our findings.


Subject(s)
DNA Helicases/genetics , DNA Repair Enzymes/genetics , Gastritis, Atrophic/genetics , Genetic Predisposition to Disease/genetics , MicroRNAs/genetics , Pepsinogen C/genetics , Polymorphism, Genetic/genetics , Stomach Neoplasms/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Female , Genotype , Humans , Male , Middle Aged , Poly-ADP-Ribose Binding Proteins , Precancerous Conditions/genetics , Risk , Young Adult
7.
Asian Pac J Cancer Prev ; 14(10): 6103-8, 2013.
Article in English | MEDLINE | ID: mdl-24289633

ABSTRACT

OBJECTIVE: Excision repair cross-complementing group 6 (ERCC6) is a major component of the nucleotide excision repair pathway that plays an important role in maintaining genomic stability and integrity. Several recent studies suggested a link of ERCC6 polymorphisms with susceptibility to various cancers. However, the relation of ERCC6 polymorphism with gastric cancer (GC) risk remains elusive. In this sex- and age- matched case-control study including 402 GC cases and 804 cancer-free controls, we aimed to investigate the association between a potentially functional polymorphism (rs1917799 T>G) in the ERCC6 regulatory region and GC risk. METHODS: The genotypes of rs1917799 were determined by Sequenom MassARRAY platform and the status of Helicobacter pylori infection was detected by enzyme-linked immunosorbent assay. Odd ratios (ORs) and 95% confidential interval (CI) were calculated by logistic regression analysis. RESULTS: Compared with the common TT genotype, the ERCC6 rs1917799 GG genotype was associated with increased GC risk (adjusted OR=1.46, 95%CI: 1.03-2.08, P=0.035). When compared with (GT+TT) genotypes, the GG genotype also demonstrated a statistical association with increased GC risk (adjusted OR=1.38, 95%CI: 1.01-1.89, P=0.044). This was also observed for the male subpopulation (GG vs. TT: adjusted OR=1.71, 95%CI: 1.12-2.62, P=0.013; G allele vs. T allele: adjusted OR=1.32, 95%CI: 1.07-1.62, P=0.009). Genetic effects on increased GC risk tended to be enhanced by H. pylori infection, smoking and drinking, but their interaction effects on GC risk did not reach statistical significance. CONCLUSIONS: ERCC6 rs1917799 GG genotype might be associated with increased GC risk in Chinese, especially in males.


Subject(s)
Asian People/genetics , DNA Helicases/genetics , DNA Repair Enzymes/genetics , Genetic Predisposition to Disease , Helicobacter pylori/pathogenicity , Polymorphism, Single Nucleotide/genetics , Stomach Neoplasms/etiology , Case-Control Studies , DNA/analysis , DNA/genetics , Enzyme-Linked Immunosorbent Assay , Female , Follow-Up Studies , Genotype , Helicobacter Infections/blood , Helicobacter Infections/complications , Helicobacter Infections/microbiology , Helicobacter pylori/metabolism , Humans , Male , Middle Aged , Neoplasm Staging , Poly-ADP-Ribose Binding Proteins , Polymerase Chain Reaction , Prognosis , Risk Factors , Stomach Neoplasms/blood , Stomach Neoplasms/pathology
8.
Histopathology ; 62(7): 1038-48, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23614500

ABSTRACT

AIMS: Mesenchyme forkhead 1 (FoxC2) is an epithelial-mesenchymal transition (EMT)-inducing factor. Previous studies have demonstrated that FoxC2 binds directly to the promoter region of p120-catenin (p120ctn). The aim of this study was to investigate the clinical significance of FoxC2 expression and the inter-relationship between FoxC2 and p120ctn, in gastric cancer. METHODS AND RESULTS: Immunohistochemistry was used to examine the expression of FoxC2 and p120ctn proteins in 325 gastric cancer samples. Staining for FoxC2 in cancer tissues was markedly stronger than in normal tissues. High FoxC2 expression was associated significantly with differentiation, invasion depth, lymph node metastasis and tumour stage. Patients with high FoxC2 expression or low p120ctn expression had a poor prognosis. In the high p120ctn expression group, the prognosis for patients with low FoxC2 expression was better than for the high FoxC2 group. Moreover, stepwise Cox regression showed that p120ctn was an independent prognostic factor, but FoxC2 in combination with p120ctn was not correlated significantly with survival. CONCLUSIONS: We found that FoxC2 and p120ctn play important roles in the progression and prognosis of gastric cancer. Moreover, FoxC2 and p120ctn should be evaluated further as novel biomarkers and therapeutic targets for gastric cancer treatment.


Subject(s)
Adenocarcinoma/secondary , Forkhead Transcription Factors/metabolism , Stomach Neoplasms/pathology , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Biomarkers, Tumor/metabolism , Catenins/metabolism , China/epidemiology , Female , Humans , Kaplan-Meier Estimate , Lymph Nodes/pathology , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging , Prognosis , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , Delta Catenin
9.
PLoS One ; 7(10): e47178, 2012.
Article in English | MEDLINE | ID: mdl-23077566

ABSTRACT

Glutathione S-transferase P1 (GSTP1) is a critical enzyme in the phase II detoxification pathway. One of the common functional polymorphisms of GSTP1 is A→G at nucleotide 313, which results in an amino acid substitution (Ile105Val) at the substrate binding site and reduced catalytic activity. We evaluated the interaction between GSTP1 Val allele and Helicobacter pylori infection, smoking and alcohol consumption, increasing the risk of gastric cancer among the Chinese population. Information on potential gastric cancer risk factors and blood specimens were collected from 618 incident gastric cancer cases and 1,830 non-cancer controls between March 2002 and December 2011 in Liaoning Province, China. GSTP1 Ile105Val was genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and polymerase chain reaction-restriction fragment length polymorphism. Serum levels of anti-H. pylori IgG were measured by ELISA. Odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariate logistic regression, adjusted by sex and age. The risk of gastric cancer was significantly elevated in patients with the GSTP1 Val/Val genotype (adjusted OR = 3.324; 95% CI = 1.790-6.172). An elevated risk of gastric cancer was observed in patients with H. pylori infection, smoking, or alcohol consumption, and together with the GSTP1 Ile/Val +Val/Val genotype (OR = 3.696; 95% CI = 2.475-5.521; OR = 1.638; 95% CI = 1.044-2.571; OR = 1.641; 95% CI = 0.983-2.739, respectively) (p<0.05). The GSTP1 Val allele shows an interaction with smoking, alcohol consumption, and especially H. pylori infection for increasing the risk of gastric cancer. These findings could demonstrate new pathophysiological pathways for the development of gastric cancer.


Subject(s)
Alcohol Drinking/adverse effects , Asian People/genetics , Glutathione S-Transferase pi/genetics , Helicobacter Infections/complications , Smoking/adverse effects , Stomach Neoplasms/genetics , Stomach Neoplasms/microbiology , China/epidemiology , Gastric Mucosa/metabolism , Helicobacter Infections/diagnosis , Helicobacter Infections/genetics , Helicobacter pylori/isolation & purification , Humans , Middle Aged , Polymorphism, Single Nucleotide , Risk Factors , Stomach/microbiology , Stomach Neoplasms/epidemiology , Valine/genetics
10.
Ann Surg ; 255(2): 208-13, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21527844

ABSTRACT

OBJECTIVE: To assess the rationality of the seventh edition of TNM staging system on tumor deposits (TDs) and propose a novel subclassification. SUMMARY BACKGROUND DATA: The TDs had been debated for many years. The seventh edition of TNM staging system proposed a "pN1c" concept. However, the value of the modification is still debated. METHODS: A total of 1541 patients with colorectal cancer were reviewed. Overall survival rates were compared between patients without LNM but TD (+), and those who were TD (-). The TDs were stratified into the "any T + any N" category. Two-step multivariate analysis was performed to identify significant prognostic factors. Univariate analysis was used to determine whether a correlation existed between the number of TDs and prognosis. RESULTS: There was a significant prognostic difference between patients without LNM or TDs compared with those with positive TDs. Only in T3N2bM0 there was a significant prognostic difference between LNM (+), TD (+) patients and TD (-) patients. The seventh edition of TNM staging system was substituted by the novel TNM staging system in 2-step multivariate analysis. Only in T3N1cM0 there was a significant prognostic difference between patients with only 1 TD and those with more than 1 TD. CONCLUSION: The seventh edition of TNM staging system on TDs satisfactorily predicts patients' outcome for those without LNM. Patients who categorized as T3N2bM0TD (+) and T4N2bM0TD (-/+) should be reclassified as stage IV. Number of TDs was not an independent prognostic parameter in the TNM staging system.


Subject(s)
Adenocarcinoma/pathology , Colorectal Neoplasms/pathology , Neoplasm Staging/methods , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/mortality , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Prognosis , Retrospective Studies , Survival Rate
11.
PLoS One ; 6(12): e28937, 2011.
Article in English | MEDLINE | ID: mdl-22174929

ABSTRACT

OBJECTIVE: The aim of the current study was to investigate which is the most suitable classification for colorectal cancer, log odds of positive lymph nodes (LODDS) classification or the classifications based on the number of positive lymph nodes (pN) and positive lymph node ratio(LNR) in a Chinese single institutional population. DESIGN: Clinicopathologic and prognostic data of 1297 patients with colorectal cancer were retrospectively studied. The log-rank statistics, Cox's proportional hazards model, the Nagelkerke R(2) index and a Harrell's C statistic were used. RESULTS: Univariate and three-step multivariate analyses identified that LNR was a significant prognostic factor and LNR classification was superior to both the pN and LODDS classifications. Moreover, the results of the Nagelkerke R(2) index (0.130) and a Harrell's C statistic (0.707) of LNR showed that LNR and LODDS classifications were similar and LNR was a little better than the other two classifications. Furthermore, for patients in each LNR classification, prognosis was homologous between those in different pN or LODDS classifications. However, for patients in pN1a, pN1b, LODDS2 and LODDS3 classifications, significant differences in survival were observed among patients in different LNR classifications. CONCLUSIONS: For patients with colorectal cancer, the LNR classification is more suitable than pN and LODDS classifications for prognostic assessment in a Chinese single institutional population.


Subject(s)
Colorectal Neoplasms/classification , Colorectal Neoplasms/pathology , Aged , Female , Humans , Lymph Nodes/pathology , Male , Middle Aged , Models, Biological , Multivariate Analysis , Neoplasm Staging , Odds Ratio , Prognosis , Survival Analysis
12.
Ann Surg Oncol ; 18(9): 2453-60, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21455596

ABSTRACT

BACKGROUND: Lymph node ratio (LNR) has been reported to represent a powerful independent prognostic value in some malignancies. The significance of LNR in colorectal cancer is still under debate. METHODS: A total of 505 patients with stage III colorectal cancer were reviewed. Using running log-rank statistics, we calculated the best cutoff values for LNRs and proposed a novel rN category: rN1, 0% < LNR ≤ 35%; rN2, 35% < LNR ≤ 69%; and rN3, LNR > 69%. A Spearman's correlation coefficient test was used to assess the correlation between the number of retrieved nodes and the number of metastatic nodes, as well as the number of retrieved nodes and the LNRs. Univariate and two-step multivariate analyses were performed, respectively, to identify the significant prognostic clinicopathologic factors. RESULTS: The 5-year overall survival rate decreased significantly with increasing LNRs: rN(1) = 61% survival rate, rN(2) = 30.3% survival rate, and rN(3) = 11.2% survival rate (P < 0.001). Univariate and two-step multivariate analyses identified the rN category as a significant prognostic factor no matter whether the minimum number of LNs retrieved was met. There was a significant prognostic difference among different rN categories for any pN category, but no apparent prognostic difference was seen between different pN categories in any rN category. Moreover, marked heterogeneity could be seen within III(a-c) substages when survival was compared among rN(1-3) categories but not between pN(1-2) categories. CONCLUSIONS: rN categories have more potential for predicting patient outcomes and are superior to the UICC/AJCC pN categories. We recommend rN categories for prognostic assessment and rN categories should be reported routinely in histopathological reports.


Subject(s)
Colorectal Neoplasms/classification , Colorectal Neoplasms/pathology , Lymph Nodes/pathology , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Retrospective Studies , Survival Rate , Young Adult
13.
Mol Cancer ; 10: 1, 2011 Jan 04.
Article in English | MEDLINE | ID: mdl-21205300

ABSTRACT

BACKGROUND: MicroRNAs (miRNAs) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Our previous studies have revealed that miR-148a and miR-152 are significantly down-regulated in gastrointestinal cancers. Interestingly, miR-148b has the same "seed sequences" as miR-148a and miR-152. Although aberrant expression of miR-148b has been observed in several types of cancer, its pathophysiologic role and relevance to tumorigenesis are still largely unknown. The purpose of this study was to elucidate the molecular mechanisms by which miR-148b acts as a tumor suppressor in gastric cancer. RESULTS: We showed significant down-regulation of miR-148b in 106 gastric cancer tissues and four gastric cancer cell lines, compared with their non-tumor counterparts by real-time RT-PCR. In situ hybridization of ten cases confirmed an overt decrease in the level of miR-148b in gastric cancer tissues. Moreover, the expression of miR-148b was demonstrated to be associated with tumor size (P = 0.027) by a Mann-Whitney U test. We also found that miR-148b could inhibit cell proliferation in vitro by MTT assay, growth curves and an anchorage-independent growth assay in MGC-803, SGC-7901, BGC-823 and AGS cells. An experiment in nude mice revealed that miR-148b could suppress tumorigenicity in vivo. Using a luciferase activity assay and western blot, CCKBR was identified as a target of miR-148b in cells. Moreover, an obvious inverse correlation was observed between the expression of CCKBR protein and miR-148b in 49 pairs of tissues (P = 0.002, Spearman's correlation). CONCLUSIONS: These findings provide important evidence that miR-148b targets CCKBR and is significant in suppressing gastric cancer cell growth. Maybe miR-148b would become a potential biomarker and therapeutic target against gastric cancer.


Subject(s)
Biomarkers, Tumor/biosynthesis , Cell Proliferation , Genes, Tumor Suppressor , MicroRNAs/biosynthesis , Stomach Neoplasms/metabolism , Animals , Biomarkers, Tumor/genetics , Case-Control Studies , Cell Line, Tumor , Down-Regulation , Female , Genes, Reporter , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , Neoplasm Transplantation , Receptor, Cholecystokinin B/biosynthesis , Receptor, Cholecystokinin B/genetics , Stomach Neoplasms/pathology , Tumor Burden
14.
Ann Surg Oncol ; 18(5): 1389-96, 2011 May.
Article in English | MEDLINE | ID: mdl-21107740

ABSTRACT

BACKGROUND: This study aimed to evaluate the prognostic impact of pT2 subclassification according to the depth of muscularis propria (MP) invasion and to explore the clinicopathologic factors correlated with lymph node metastasis (LNM) and postoperative hematogenous metastasis in pT2 colorectal cancer. METHODS: A total of 317 patients with pT2 colorectal cancer were reviewed. pT2a represents the infiltration of the inner circumferential layer of the MP, and pT2b represents the infiltration of the outer longitudinal layer of the MP. Clinicopathologic factors and overall survival rates were compared in patients with pT2a and pT2b stage cancers. Multivariate analysis was performed to identify the significantly important prognostic factors. Univariate and multivariate analyses were performed, respectively, to identify the significantly important clinicopathologic factors correlated with LNM and postoperative hematogenous metastasis in pT2 colorectal cancer. RESULTS: According to the depth of MP invasion, 107 patients were classified as pT2a and 210 patients were classified as pT2b. Among them, there were 55 patients with LNM, 34 patients with postoperative hematogenous metastasis. There was significant difference in most of clinicopathologic features between patients in the pT2a and pT2b stages. Multivariate analysis identified pN stage (P < .001) and tumor location (P = .036) were independent factors affecting the prognosis. However, no apparent difference was observed between pT2a versus pT2b cancer. Univariate and multivariate analyses uniformly identified lymphovascular invasion (P = .035) and the depth of MP invasion (P = .005) as significantly correlated with LNM. Multivariate analysis found tumor location (P = .021) and the presence or absence of LNM (P < .001) were important factors affecting postoperative hematogenous metastasis. CONCLUSIONS: In pT2 colorectal cancer treated with R0 surgery, there is a high risk of LNM in deep MP invasion versus superficial MP invasion. The pT2 subclassification system had no significant advantage in identifying a different prognosis, except for predicting the LNM before surgery. Rectal cancer and the presence of LNM were high-risk factors resulting in hematogenous metastasis postoperatively.


Subject(s)
Colorectal Neoplasms/classification , Colorectal Neoplasms/pathology , Neoplasm Recurrence, Local/mortality , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/surgery , Female , Follow-Up Studies , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Recurrence, Local/diagnosis , Neoplasm Staging , Predictive Value of Tests , Prospective Studies , Risk Assessment , Survival Rate
15.
Zhonghua Zhong Liu Za Zhi ; 28(2): 120-2, 2006 Feb.
Article in Chinese | MEDLINE | ID: mdl-16750016

ABSTRACT

OBJECTIVE: To study the expression and significance of interleukin-8 (IL-8), cyclooxygenase-2 (COX-2) and trefoil family factor 1 (TFF1) in the remnant stomach mucosa. METHODS: Patients after gastrectomy were examined by upper gastrointestinal endoscopy. Biopsy specimens were obtained from stoma and the greater curvature of the upper corpus to be assessed for Hp (by H.E. and Giemsa staining) and conduct real-time semi-quantitative PCR. mRNA was extracted from the biopsy specimens to determine the IL-8, COX-2 and TFF1 gene mRNA levels by real-time PCR method. RESULTS: In the stoma, COX-2 level in Hp-positive patients was significantly higher than that in Hp-negative patients, but the difference of IL-8 levels between them was not significant. In the corpus, IL-8 and COX-2 levels in Hp-positive patients were significantly higher than those in Hp-negative patients. In Hp-negative patients, IL-8 and COX-2 levels in the stoma were significantly higher in B II anastomosis than in B I anastomosis cases; COX-2 level in the stoma was significantly higher in B II anastomosis than in B I anastomosis cases, but the difference of IL-8 levels between them was not significant. TFF1 level in the remnant stomach mucosa showed no significant difference between Hp-positive and Hp-negative patients. CONCLUSION: Hp infection and bile reflux are important risk factors for the secondary stomach carcinogenesis. Expression of IL-8 and COX-2 in the remnant stomach mucosa is related to the risk of secondary stomach carcinogenesis. The relationship between the TFF1 expression and secondary stomach carcinogenesis in the remnant stomach mucosa is still unclear and should further be studied.


Subject(s)
Cyclooxygenase 2/biosynthesis , Gastric Stump , Interleukin-8/biosynthesis , Stomach Neoplasms/metabolism , Tumor Suppressor Proteins/biosynthesis , Adult , Aged , Aged, 80 and over , Cyclooxygenase 2/genetics , Female , Gastrectomy , Gastric Mucosa/metabolism , Helicobacter Infections/metabolism , Helicobacter pylori , Humans , Interleukin-8/genetics , Male , Middle Aged , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Risk Factors , Stomach Neoplasms/microbiology , Stomach Neoplasms/surgery , Trefoil Factor-1 , Tumor Suppressor Proteins/genetics
16.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 21(4): 503-5, 2005 Jul.
Article in Chinese | MEDLINE | ID: mdl-15989802

ABSTRACT

AIM: To explore the relationship between helicobacter pylori (Hp) infection and expression of interleukin-8 (IL-8) in the remnant stomach mucosa. METHODS: Fifty-eight patients with gastrectomy were examined by upper gastrointestinal endoscopy. Biopsy specimens were obtained from stoma and the greater curvature of the upper corpus to detect Hp infection (by H.E. and Giemsa staining) and IL-8 expression (by real-time semi-quantitative RT-PCR). RESULTS: Hp infection was detected in 65.5% (38/58)of the remnant stomach mucosa. In 34 patients with Billroth I (BI) anastomosis, IL-8 in corpus was significantly higher in Hp-positive patients than that in Hp-negative patients (0.11+/-0.07 vs 0.02+/-0.01, P<0.05). In 24 patients with Billroth II (BII) anastomosis, IL-8 in stoma and corpus in Hp-positive patients was significantly higher than that in Hp-negative patients (P<0.05). CONCLUSION: Hp infection induces IL-8 expression in remnant stomach mucosa. In corpus, IL-8 mRNA expression is mainly related with Hp infection, while in stoma, IL-8 mRNA expressions may be related with bile reflux besides Hp infection.


Subject(s)
Gastric Mucosa/immunology , Gastric Mucosa/microbiology , Gastric Stump , Gene Expression Regulation , Helicobacter Infections/genetics , Helicobacter pylori , Interleukin-8/genetics , Adult , Aged , Aged, 80 and over , Endoscopes, Gastrointestinal , Female , Gastric Mucosa/metabolism , Gastric Mucosa/surgery , Gastroenterostomy , Helicobacter Infections/immunology , Humans , Male , Middle Aged , RNA, Messenger/genetics , RNA, Messenger/metabolism
17.
Zhonghua Wai Ke Za Zhi ; 43(3): 166-8, 2005 Feb 01.
Article in Chinese | MEDLINE | ID: mdl-15842895

ABSTRACT

OBJECTIVE: To study the expressions and the significance of interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2) in the remnant stomach. METHODS: Fifty-eight patients with gastrectomy were examined by upper gastrointestinal endoscopy. Two biopsy specimens were obtained from the stoma and the upper corpus gastric mucosa in the remnant stomach. mRNA was extracted from biopsy specimens to measure the IL-8 and COX-2 gene mRNA levels by real-time PCR method. RESULTS: IL-8 and COX-2 levels were higher in stoma than in corpus, IL-8 levels in BI anastomosis were significantly higher in stoma than in corpus (P< 0.05). In Hp-negative patients, IL-8 and COX-2 levels in stoma were significantly higher in BII anastomosis than in BI anastomosis (P < 0.05). In Hp-positive patients, IL-8 and COX-2 levels in stoma showed no significant differences between BII anastomosis and BI anastomosis. In corpus, IL-8 and COX-2 levels in Hp-positive patients were significantly higher than those in Hp-negative patients, (P < 0.05), including in BI anastomosis and in BII anastomosis. CONCLUSIONS: The risk of the secondary stomach carcinogenesis in stoma after distal gastrectomy is higher than that in corpus; The types of anastomosis may influence the risk for the secondary stomach carcinogenesis in the remnant stomach mucosa.


Subject(s)
Gastric Mucosa/metabolism , Gastric Stump/surgery , Gastroenterostomy/methods , Interleukin-8/biosynthesis , Prostaglandin-Endoperoxide Synthases/biosynthesis , Stomach Neoplasms/etiology , Adult , Aged , Aged, 80 and over , Female , Gastric Mucosa/microbiology , Gastroenterostomy/adverse effects , Helicobacter Infections , Helicobacter pylori , Humans , Interleukin-8/genetics , Male , Middle Aged , Prostaglandin-Endoperoxide Synthases/genetics , RNA, Messenger/biosynthesis
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