SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer

AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients. METHODS: One hundred and fifty-six CRC patientswere followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was performed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics analysis involving a Support Vector Machine (SVM) was used to determine the best prognostic model from combinations of these markers. RESULTS: Seven markers (SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK) were significantly related to the prognosis and clinical pathological features of the CRC patients (P < 0.05). Prognostic models were established through SVM from combinations of these 7 markers and proved able to differentiate patients with dissimilar survival, especially in stage Ⅱ/Ⅲ patients. According to the best prognostic model, the p53/SPARCL1 model, patients having high p53 and low SPARCL1 expression had about 50% lower 3-year survival than others (P < 0.001). CONCLUSION: SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are potential prognostic markers in CRC. A p53/SPARCL1 bioinformatics model may be used as a supplement to tumor-nodes-metastasis staging.

Indoleamine-2,3-dioxygenase 1/cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer

AIM To evaluate indoleamine-2,3-dioxygenase 1/cyclooxygenase 2(IDO1/COX2) expression as an independent prognostic biomarker for colorectal cancer(CRC) patients.METHODS We retrospectively studied the medical records of 95 patients who received surgical resection from August 2008 to January 2010. All patients were randomly assigned to adjuvant treatment with or without celecoxib groups after surgery. We performed standard immunohistochemistry to assess the expression levels of IDO1/COX2 and evaluated the correlation of IDO1/COX2 with clinicopathological factors and overall survival(OS) outcomes.RESULTS The expression of nuclear IDO1 was significantly correlated with body mass index(P < 0.001), and IDO1 expression displayed no association with sex, age, tumor differentiation, T stage, N stage, carcinoembryonic antigen, cancer antigen 19-9, CD3+ and CD8+ tumor infiltrating lymphocytes, and COX2. In univariate analysis, we found that nuclear IDO1(P = 0.039), nuclear/cytoplasmic IDO1 [hazard ratio(HR) = 2.044, 95% confidence interval(CI): 0.871-4.798, P = 0.039], nuclear IDO1/COX2(HR = 3.048, 95%CI: 0.868-10.7, P = 0.0049) and cytoplasmic IDO1/COX2(HR = 2.109, 95%CI: 0.976-4.558, P = 0.022) all yielded significantly poor OS outcomes. Nuclear IDO1(P = 0.041), nuclear/cytoplasmic IDO1(HR = 3.023, 95%CI: 0.585-15.61, P = 0.041) and cytoplasmic IDO1/COX2(HR = 2.740, 95%CI: 0.764-9.831, P = 0.038) have significantly poor OS outcomes for the CRC celecoxib subgroup. In our multivariate Cox model, high coexpression of cytoplasmic IDO1/COX2 was found to be an independent predictor of poor outcome in CRC(HR = 2.218, 95%CI: 1.011-4.48, P = 0.047) and celecoxib subgroup patients(HR = 3.210, 95%CI: 1.074-9.590, P = 0.037).CONCLUSION Our results showed that cytoplasmic IDO1/COX2 coexpression could be used as an independent poor predictor for OS in CRC.

Role of doublecortin-like kinase 1 and leucine-rich repeat-containing G-protein-coupled receptor 5 in patients with stage Ⅱ/Ⅲ colorectal cancer:Cancer progression and prognosis

BACKGROUND Cancer stem cells(CSCs)are a subpopulation of cancer cells with the potential of self-renewal and differentiation.CSCs play critical roles in tumorigenesis,recurrence,metastasis,radiation tolerance and chemoresistance.AIM To assess the expression patterns and clinical potential of doublecortin-like kinase 1(DCLK1)and leucine-rich repeat-containing G-protein-coupled receptor 5(Lgr5),as prognostic CSC markers of colorectal cancer(CRC).METHODS The expression of DCLK1 and Lgr5 in CRC tissue sections from 92 patients was determined by immunohistochemistry.Each case was evaluated using a combined scoring method based on signal intensity staining(scored 0-3)and the proportion of positively stained cancer cells(scored 0-3).The final staining score was calculated as the intensity score multiplied by the proportion score.Low expression of DCLK1 and Lgr5 was defined as a score of 0-3;high expression of DCLK1 and Lgr5 was defined as a score of≥4.Specimens were categorized as either high or low expression,and the correlation between the expression of DCLK1 or Lgr5 and clinicopathological factors was investigated.RESULTS DCLK1 and Lgr5 expression levels were significantly positively correlated.CRC patients with high DCLK1,Lgr5 and DCLK1/Lgr5 expressions had poorer progression-free survival and overall survival.Moreover,high expression of DCLK1 was an independent prognostic factor for recurrence and overall survival in patients with CRC by multivariate analysis(P=0.026 and P=0.049,respectively).CONCLUSION DCLK1 may be a potential CSC marker for the recurrence and survival of CRC patients.

Prognostic value of lymph node metastasis in patients with T1-stage colorectal cancer from multiple centers in China

AIM To explore the features and prognostic value of lymph node metastasis in patients with T1-stage colorectal cancer(CRC).METHODS In all,321 cases of T1-stage CRC were selected from 10132 patients with CRC who received surgical therapy in six large-scale hospitals in China and were retrospectively analyzed. Univariate and multivariate analyses were performed to analyze the risk factors for lymphatic metastasis. A survival analysis was then performed to analyze the prognostic value of lymph node metastasis.RESULTS The occurrence rate of T1 stage was 3.17%(321/10132);of these patients,the lymph node metastasis rate was 8.41%(27/321),and the non-lymph node metastasis rate was 91.59%(294/321). Univariate analysis showed that preoperative serum CEA,preoperative serum CA199,preoperative serum CA724,vascular invasion,and degree of differentiation were associated with lymph node metastasis in T1-stage CRC(P < 0.05 for all). Multivariate analysis indicated that preoperative serum CA724,vascular invasion,and degree of differentiation were closely related to lymph node metastasis(P < 0.05 for all). Log-rank survival analysis showed that age,preoperative serum CEA,preoperative serum CA199,vascular invasion,degree of differentiation,and lymph node metastasis(χ2 = 24.180,P < 0.001) were predictors of 5-year overall survival(OS)(P < 0.05 for all). COX regression analysis demonstrated that preoperative serum CA199 and lymph node metastasis(HR = 5.117;P < 0.05;95%CI: 0.058-0.815) were independent prognostic indicators of 5-year OS in patients with T1-stage CRC(P < 0.05 for both). CONCLUSION The morbidity of T1-stage CRC was 3.17% for all CRC cases. Preoperative serum CA724,vascular invasion,and degree of differentiation are independent risk factors for lymph node metastasis. Lymph node metastasis is an independent prognostic factor for OS in patients with T1-stage CRC.

Predictive and prognostic implications of 4E-BP1, Beclin-1, and LC3for cetuximab treatment combined with chemotherapy in advanced colorectal cancer with wild-type KRAS: Analysis from real-world data

BACKGROUND Colorectal cancer(CRC) is one of the main causes of cancer-related deaths in China and around the world. Advanced CRC(ACRC) patients suffer from a low cure rate though treated with targeted therapies. The response rate is about 50% to chemotherapy and cetuximab, a monoclonal antibody targeting epidermal growth factor receptor(EGFR) and used for ACRC with wild-type KRAS. It is important to identify more predictors of cetuximab efficacy to further improve precise treatment. Autophagy, showing a key role in the cancer progression, is influenced by the EGFR pathway. Whether autophagy can predict cetuximab efficacy in ACRC is an interesting topic.AIM To investigate the effect of autophagy on the efficacy of cetuximab in colon cancer cells and ACRC patients with wild-type KRAS.METHODS ACRC patients treated with cetuximab plus chemotherapy, with detailed data and tumor tissue, at Sun Yat-sen University Cancer Center from January 1, 2005,to October 1, 2015, were studied. Expression of autophagy-related proteins[Beclin1, microtubule-associated protein 1 A/B-light chain 3(LC3), and 4 Ebinding protein 1(4 E-BP1)] was examined by Western blot in CRC cells and by immunohistochemistry in cancerous and normal tissues. The effect of autophagy on cetuximab-treated cancer cells was confirmed by MTT assay. The associations between Beclin1, LC3, and 4 E-BP1 expression in tumor tissue and the efficacy of cetuximab-based therapy were analyzed.RESULTS In CACO-2 cells exposed to cetuximab, LC3 and 4 E-BP1 were upregulated, and P62 was downregulated. Autophagosome formation was observed, and autophagy increased the efficacy of cetuximab. In 68 ACRC patients,immunohistochemistry showed that Beclin1 levels were significantly correlated with those of LC3(0.657, P < 0.001) and 4 E-BP1(0.211, P = 0.042) in ACRC tissues.LC3 was significantly overexpressed in tumor tissues compared to normal tissues(P < 0.001). In 45 patients with wild-type KRAS, the expression levels of these three proteins were not related to progression-free survival; however, the expression levels of Beclin1(P = 0.010) and 4 E-BP1(P = 0.005), pathological grade(P = 0.002), and T stage(P = 0.004) were independent prognostic factors for overall survival(OS).CONCLUSION The effect of cetuximab on colon cancer cells might be improved by autophagy.LC3 is overexpressed in tumor tissues, and Beclin1 and 4 E-BP1 could be significant predictors of OS in ACRC patients treated with cetuximab.

Loss of stromal caveolin-1 expression in colorectal cancer predicts poor survival

AIM: To investigate the clinicopathological significance and prognostic value of caveolin-1(CAV-1) in both tumor and stromal cells in colorectal cancer(CRC).METHODS: A total of 178 patients with CRC were included in this study. The correlation between CAV-1expression and clinicopathologic features and survival was studied.RESULTS: CAV-1 expression was detected in tumor and stromal cells. The expression of stromal CAV-1 was closely associated with histological type(P = 0.022), pathologic tumor-node-metastasis stage(P = 0.047), pathologic N stage(P = 0.035) and recurrence(P = 0.000). However, tumor cell CAV-1 did not show any correlation with clinical parameters. Additionally, the loss of stromal CAV-1 expression was associated with shorter disease-free survival(P = 0.000) and overall survival(P = 0.000). Multivariate analysis revealed that the loss of stromal CAV-1 expression was an independent prognostic factor for both overall survival(P = 0.014) and disease-free survival(P = 0.006).CONCLUSION: The loss of stromal CAV-1 expression in CRC was associated with poor prognosis and could be a prognostic factor for CRC patients.

Correlation between mitochondrial TRAP-1 expression and lymph node metastasis in colorectal cancer

AIM： To evaluate the effect of mitochondrial tumor ne- crosis factor receptor-associated protein-1 （TRAP-l） on the lymph node metastasis （LNM） in Chinese colorectal cancer （CRC） patients, and develop potential LNM- associated biomarkers for CRC using quantitative real- time polymerase chain reaction （RT-PCR） analysis. METHODS： Differences in mitochondrial TRAP-1 gene expression between primary CRC with LNM （LNM CRC） and without LNM （non-LNM CRC） were assessed in 96 Chinese colorectal carcinoma samples using quantita- tive RT-PCR analysis, Western blotting, and confirmed with immunohistochemical assay. The relationship between clinicopathological parameters and potential diaclnostic biomarkers was also examined.RESULTS： TRAP-1 was significantly upregulated in LNM CRC compared with non-LNM CRC, which was confirmed by RT-PCR, Western blotting and immuno- histochemical assay. The expression of TRAP-1 in two different metastatic potential human colorectal cancer cell lines, LoVo and HT29, was analyzed with Western blotting. The expression level of TRAP-1 was dramati- cally higher in LoVo than in HT29. Overexpression of TRAP-1 was significantly associated with LNM （90.2% in LNM group vs 22% in non-LNM group, P 〈 0.001）, the advanced tumor node metastasis stage （89.1% in LNM group vs 26.9% in non-LNM group, P 〈 0.001）, the increased 5-year recurrence rate （82.7% in LNM group vs 22.6% in non-LNM group, P 〈 0.001） and the decreased 5-year overall survival rate （48.4% in LNM vs 83.2% in non-LNM group, P 〈 0.001）. Univariate and multivariate analyses indicated that TRAP-1 expression was an independent prognostic factor for recurrence and survival of CRC patients （Hazard ratio of 2.445 in recurrence, P = 0.017; 2.867 in survival, P = 0.028）. CONCLUSION： Mitochondria TRAP-1 affects the lymph node metastasis in CRC, and may be a potential bio- marker for LNM and a prognostic factor in CRC. Over- expression of TRAP-1 is a predictive factor for the poor outcome of colorectal cancer patients. 2012 Baishideng. All rights reserved

Clinicopathologic and prognostic relevance of ARID1A protein loss in colorectal cancer

AIM: To explore the association between AT-rich interactive domain 1A (ARID1A) protein loss by immunohistochemistry and both clinicopathologic characteristics and prognosis in patients with colorectal cancer.

Stanniocalcin-1 Detection of Peripheral Blood in Patients with Colorectal Cancer

Objective： Stanniocalcin-1 （STC-1）, a kind of glycoprotein hormone, is universally up-regulated in various tumor tissues compared to corresponding normal tissues, suggesting it may be used as a tumor marker, whilst disseminated tumor cells usually exist in peripheral blood. The aim of this study is to investigate the mRNA expression STC-1 in peripheral blood of colorectal cancer （CRC） and analyze its clinicopathological significance. Methods： The peripheral blood mononuclear cells （PBMNCs） were isolated from 78 CRC patients and 33 cancer-free controls. The expression status of STC-1 mRNA in PBMNCs was assessed by RT-PCR, its correlation with clinicopathological parameters and 5-year overall survival was analyzed as well. Results： In the 78 blood samples from CRC patients, 33 （42.31%） showed positive expression of STC-1 mRNA, and all of 15 gastrointestinal tumor tissues were positive for STC-1 mRNA. In contrast, all the blood samples from 14 healthy donors and 19 patients with inflammatory gastrointestinal disease were negative. Furthermore, STC-1 mRNA expression status was associated with patients’ advanced stage, distant metastasis and shortened overall survival. Conclusion： The detection of STC-1 mRNA in peripheral blood by RT-PCR was highly sensitive and specific for the patients with CRC. STC-1 mRNA may be a potential biomarker for detecting tumor micrometastasis and predicting prognosis.

Clinical assessment and identification of immuno-oncology markers concerning the 19-gene based risk classifier in stage Ⅳ colorectal cancer

BACKGROUND Genomic profiling of tumors has contributed to the understanding of colorectal cancer(CRC), facilitating diagnosis, prognosis and selection of treatments,including targeted regimens. A report suggested that a 19-gene-based risk classifier(TCA19) was a prognostic tool for patients with stage III CRC. The survival outcomes in patients with stage IV CRC are still poor and appropriate selection of targeted therapies and immunotherapies is challenging.AIM To assess clinical implication of TCA19 in patients with stage IV CRC, and to identify TCA19 with involvement in immune-oncology.METHODS A retrospective review of the medical records of 60 patients with stage IV CRC was conducted, assessing clinicopathological variables and progression-free survival(PFS). TCA19 gene expression was determined by quantitative polymerase chain reaction(qPCR) in matched normal and tumor tissues taken from the study cohort. Expression of potential immune-oncology regulatory proteins and targets was examined by immunohistochemistry(IHC), western blot, immunofluorescence staining in tissues from a validation cohort of 10 patients, and in CRC cell lines co-cultured with monocyte in vitro.RESULTS In the patients with TCA19 score higher than the median, the PFS rates of eight patients who received the targeted regimens were significantly higher than the PFS rates of four patients who received 5-fluorouracil-based regimen(P = 0.041).In multivariate analysis, expression of signaling lymphocytic activation molecule family, member 7(SLAMF7) and triggering receptor expressed on myeloid cells 1(TREM1) was associated with PFS in the 60-patient cohort. After checking another 10 validate set, the expression of the IHC, the level of real-time qPCR,and the level of western blot were lower for SLAMF7 and higher for TREM7 in primary and metastatic tumors than in normal tissues. In CRC cells expressing SLAMF7 that were co-cultured with a monocytic cell line, levels of CD 68 and CD73 were significantly lower at day 5 of co-culture than at day 0.CONCLUSION The TCA19 score might be prognostic for target-regimen-specific PFS in stage IV CRC. Down-regulation of SLAMF7 and up-regulation of TREM1 occur in primary and metastatic tumor tissues.

Pathological significance of abnormal recepteur d'origine nantais and programmed death ligand 1 expression in colorectal cancer

BACKGROUND Programmed death ligand 1(PD-L1) immunotherapy remains poorly efficacious in colorectal cancer(CRC). The recepteur d'origine nantais(RON) receptor tyrosine kinase plays an important role in regulating tumor immunity.AIM To identify the patterns of RON and PD-L1 expression and explore their clinical significance in CRC.METHODS Gene expression data from the Gene Expression Omnibus database(GEO;n = 290) and patients at the First Affiliated Hospital, Zhejiang University School of Medicine(FAHZUSM;n = 381) were analyzed to determine the prognostic value of RON and PD-L1 expression within the tumor microenvironment of CRC. HT29 cell line was treated with BMS-777607 to explore the relationship between RON activity and PD-L1 expression. Signaling pathways and protein expression perturbed by RON inhibition were evaluated by cellular immunofluorescence and Western blot.RESULTS In the GEO patient cohort, cut-off values for RON and PD-L1 expression were determined to be 7.70 and 4.3, respectively. Stratification of patients based on these cutoffs demonstrated that high expression of RON and PD-L1 was associated with a poor prognosis. In the FAHZUSM cohort, rates of high expression of RON in tumor cells, high PD-L1 expression in tumor cells and tumor infiltrating monocytes, and both high RON and high PD-L1 expression in the tumor microenvironment were 121(32%), 43(11%), 91(24%), and 51(13.4%), respectively. High expression of RON was significantly correlated with high expression of PD-L1 in the tumor cell compartment(P < 0.001). High expression of RON and that of PD-L1 were independent prognostic factors for poorer overall survival. Concurrent high expression of both RON and PD-L1 in the tumor microenvironment was significantly associated with a poor prognosis. In vitro, BMS-777607 inhibited the phosphorylation of RON, inhibited PD-L1 expression, and attenuated activation of the ERK1/2 and AKT signaling pathways in CRC cells.CONCLUSION RON, PD-L1, and their crosstalk are significant in predicting the prognostic value of CRC. Moreover, phosphorylation of RON upregulates PD-L1 expression, which provides a novel approach to immunotherapy in CRC.

Prognostic significance of PD-L1 expression in patients with colorectal cancer: a meta-analysis

Background The association between the expression of programmed cell death 1(PD-1) or its ligand [programmed cell death ligand-1(PD-L1)] and colorectal cancer(CRC) survival rates remains unclear. Thus, we conducted a meta-analysis to investigate the prognostic value of PD-L1 expression in CRC patients.Methods All eligible studies related to evaluation of PD-L1 expression and survival of CRC patients were searched in PubMed, Medline, Cochrane library, and the EMBASE database. Hazard ratios(HRs) and 95% confidence intervals(CI) of overall survival(OS) were examined to assess the effect of PD-L1 expression on the survival of CRC patients. The outcomes of this meta-analysis were synthesized based on randomeffects model. Subgroup analyses were also performed. Results Seven studies, wherein OS data were stratified according to the expression status of PD-L1, were analyzed. CRC patients showing positive PD-L1 expression were associated with significantly poorer prognoses in terms of overall survival, compared with those displaying negative PD-L1 expression(HR = 1.43, 95% CI: 1.07–1.92; P = 0.02). In the subgroup analyses, H-scores as well as the percentage of stained cells indicated that PD-L1 expression was significantly associated with poor prognosis(HR = 1.90, 95% CI: 1.38–2.62, P < 0.01; HR = 1.81, 95% CI: 1.08–3.03, P = 0.02). Immunohistochemical staining, utilizing a rabbit anti-PD-L1 antibody, revealed significantly superior survival in the PD-L1 negative group compared with the PD-L1 positive expression group(HR = 1.92; 95% CI, 1.40-2.63; P < 0.01). Moreover, PD-L1 expression was significantly associated with poor prognosis when polyclonal antibodies were used(HR = 1.84; 95% CI, 1.30–2.61; P < 0.01). Conclusion Our meta-analysis indicated that PD-L1 expression status is a significant prognostic factor for CRC patients. Positive PD-L1 expression was associated with worse CRC survival. Evaluation via different immunohistochemistry based techniques may partly account for the contradictory results. Therefore, further investigative studies using larger sample sizes are felt to be needed to elucidate the prognostic value of PD-L1 expression in CRC patients.

结直肠癌组织中lncRNA CCAT2和NDRG1的表达及意义

目的探讨结直肠癌(CRC)患者组织中长链非编码RNA(lncRNA)结肠癌相关转录物2(CCAT2)、N-myc下游调节基因(NDRG)1的表达及与临床病理特征及预后的关系。方法选取2018年2月至2020年2月在南通市中医院行CRC根治性手术治疗的96例CRC患者作为研究对象。采用实时荧光定量PCR检测组织中lncRNA CCAT2、NDRG1 mRNA表达,采用免疫组织化学检测组织中NDRG1蛋白表达,采用Kaplan-Meier曲线分析不同lncRNA CCAT2、NDRG1 mRNA表达组患者的预后差异,采用多因素Cox回归分析CRC预后影响因素。结果与癌旁组织比较,癌组织中lncRNA CCAT2表达较高,NDRG1 mRNA表达及蛋白阳性率较低,差异有统计学意义(P<0.05)。与TNM分期Ⅰ~Ⅱ期、无淋巴结转移比较,TNM分期Ⅲ期、有淋巴结转移的CRC患者癌组织中lncRNA CCAT2表达较高,NDRG1 mRNA表达较低(P<0.05)。lncRNA CCAT2高表达组3年累积生存率低于lncRNA CCAT2低表达组,而NDRG1 mRNA高表达组3年累积生存率高于NDRG1 mRNA低表达组,差异有统计学意义(P<0.05)。TNM分期、淋巴结转移,lncRNA CCAT2、NDRG1 mRNA是CRC预后影响因素(P<0.05)。结论CRC组织中lncRNA CCAT2表达升高,NDRG1表达降低,二者均参与CRC肿瘤的进展,可作为评估CRC患者生存预后的新指标。

结直肠癌组织miR-330-5p、PTBP1的表达与病理参数和预后的关系

目的分析结直肠癌组织微小核糖核酸-330-5p(miR-330-5p)、多聚嘧啶区结合蛋白1(PTBP1)的表达与病理参数及预后的关系。方法选取2018年1月—2020年5月南通市中医院肛肠科收治的结直肠癌患者101例,收集术中部分癌组织及其癌旁组织,采用实时荧光定量聚合酶链式反应检测miR-330-5p、PTBP1 mRNA表达。通过Targetscan数据库预测miR-330-5p与PTBP1的结合位点,分析miR-330-5p、PTBP1 mRNA在结直肠癌组织不同临床病理参数中的差异;采用K-M法绘制其生存曲线;多因素Cox回归分析患者预后影响因素。结果与癌旁组织比较,结直肠癌组织miR-330-5p表达降低,PTBP1 mRNA表达升高(t/P=24.000/<0.001、19.233/<0.001)。miR-330-5p与PTBP1存在结合位点,二者在结直肠癌组织表达呈负相关(r/P=-0.679/<0.001)。与低分化程度、TNMⅢ期、有淋巴结转移比较,中高分化程度、TNMⅠ~Ⅱ期、无淋巴结转移结直肠癌组织miR-330-5p升高、PTBP1 mRNA表达降低(t/P=2.490/0.014、2.479/0.015,2.837/0.006,2.953/0.004,3.319/0.001、3.307/0.001)。101例结直肠癌患者3年总生存率为83.17%(84/101)。miR-330-5p高表达组、PTBP1 mRNA低表达组3年总生存率分别高于miR-330-5p低表达组、PTBP1 mRNA高表达组(χ^(2)/P=6.466/0.011、11.697/0.001)。结直肠癌患者死亡的独立危险因素为低分化、TNM分期Ⅲ期、淋巴结转移和PTBP1 mRNA≥1.50,独立保护因素为miR-330-5p≥0.57[OR(95%CI)=3.642(1.278~10.381)、3.817(1.375~10.598)、4.013(1.418~11.351)、2.684(1.025~7.029)、0.338(0.129~0.890)]。结论结直肠癌组织miR-330-5p低表达和PTBP1 mRNA高表达,与分化程度、TNM分期、淋巴结转移和预后有关。

结直肠癌p53和DNA损伤调节基因1的表达及临床意义

目的 分析p53和DNA损伤调节基因1(p53 and DNA damage regulated gene 1,PDRG1)在结直肠癌中的表达及其临床意义。方法 检索癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中结直肠癌数据集,比较PDRG1 mRNA在结直肠癌组织和正常结直肠组织中的表达差异,分析其表达与临床病理特征及预后的关系。DNA甲基化交互可视化数据库(DNA methylation interactive visualization database,DNMIVD)分析PDRG1基因甲基化与m RNA表达水平的关系。另选取本院2019年2月至2020年5月存档的102例结直肠癌组织及其癌旁正常结直肠组织石蜡标本进行验证,采用免疫组织化学法检测PDRG1蛋白的表达。结果 TCGA数据库分析发现,PDRG1 mRNA在结直肠癌组织(n=284)中的表达较正常结直肠组织(n=41)增高(P<0.01),且结直肠癌PDRG1 mRNA表达与拷贝数变异呈正相关(n=273;r=0.792,P<0.01)。DNMIVD分析显示,PDRG1启动子甲基化β值与基因表达水平呈负相关(r=-0.34,P<0.01)。TCGA数据库分析显示,结直肠癌患者(n=273)PDRG1 mRNA表达在肿瘤位置、TNM分期及远处转移方面比较,差异均具有统计学意义(均P<0.05);对245例结直肠癌患者进行Kaplan-Meier生存分析发现,PDRG1 mRNA高表达患者(以中位数为分界值,大于中位数为高表达)无瘤生存期较短(P=0.019)。免疫组织化学检测显示,结直肠癌组织中PDRG1蛋白表达阳性率高于正常结直肠癌组织[87.3%(89/102) vs32.4%(33/102),P<0.01]。结论 PDRG1在结直肠癌中高表达,且与肿瘤位置、远处转移和无瘤生存期有关,可能成为结直肠癌潜在的生物标志物。

结直肠癌组织中NR2F1的表达及其与预后的相关性

目的检测结直肠癌中核受体亚家族2组F成员1(NR2F1)的蛋白表达水平,并探讨其与患者预后的关系。方法选择2012年8月至2013年9月在苏州市立医院进行根治性切除术的56例结直肠癌患者作为研究对象,采集患者的结直肠癌组织标本及对应的癌旁组织标本。采用EnVision法测定结直肠癌组织和癌旁组织的NR2F1的蛋白表达水平,比较不同NR2F1蛋白表达水平结直肠癌患者的临床病理特征。采用Kaplan-Meier法绘制结直肠癌患者的生存曲线,分析NR2F1蛋白表达水平与结直肠癌的预后的相关性。结果结直肠癌组织的NR2F1高表达率为48.21%,明显高于癌旁组织的7.14%,差异有统计学意义(P<0.05);NR2F1高表达者的无脉管侵犯率为85.19%,明显高于NR2F1低表达者的58.62%,差异有统计学意义(P<0.05);NR2F1高表达患者突破浆膜层的占比为48.15%,明显低于NR2F1低表达者的65.52%,且随着浸润深度从固有肌层到突破浆膜层,NR2F1低表达增加,差异均具有统计学意义(P<0.05);NR2F1高表达和低表达患者在性别、年龄、肿块大小、分化程度、淋巴结转移方面比较,差异均无统计学意义(P>0.05);经Kaplan-Meier生存曲线分析结果显示,结直肠癌的NR2F1高表达患者的10年总生存率为26.79%,明显高于NR2F1低表达患者的17.86%,差异有统计学意义(P<0.05)。结论结直肠癌的NR2F1表达升高,NR2F1可能参与了结直肠癌的发生、侵袭,对患者的预后造成一定的影响。

结直肠癌和不同类型结直肠息肉中LYVE-1标记的淋巴管密度及其临床意义

目的探讨淋巴管内皮透明质酸受体-1(LYVE-1)标记的淋巴管密度(LVD)在结直肠癌和不同类型结直肠息肉中的差异及其临床意义。方法通过免疫组化法对60例结直肠息肉和18例结直肠癌中LYVE-1标记的淋巴管进行计数,分析结直肠癌和不同类型结直肠息肉中LVD的差异。结果结直肠癌中LVD显著高于结直肠息肉[(6.7±1.3)个vs(3.5±1.1)个,P<0.001]。不同类型的结直肠息肉中,炎性息肉中LVD低于腺瘤性息肉和锯齿状病变[(2.1±0.7)个vs(3.6±0.7)个,(4.1±1.1)个,P<0.05]。直径≥10 mm的息肉中LVD高于直径<10 mm的息肉[(3.6±1.1)个vs(2.7±1.0)个,P<0.05]。伴有异形增生的息肉中LVD显著高于不伴有异形增生的息肉[(4.0±1.0)个vs(3.0±1.0)个,P<0.001]。而LVD在不同性别、年龄、息肉位置方面差异均无统计学意义(P>0.05)。结论LVD有可能作为反映结直肠息肉预后的重要指标,为结直肠息肉患者术后随访间隔与结直肠癌的预测提供新的理论参考。

Novel parameter based on lipid indicators ratio improves prognostic value of plasma lipid levels in resectable colorectal cancer patients

BACKGROUND At present,the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited.AIM To evaluate the value of a novel parameter for colorectal cancer(CRC)prognosis scoring based on preoperative serum lipid levels.METHODS Four key serum lipid factors,namely,high-density lipoprotein cholesterol(HDLC),low-density lipoprotein cholesterol(LDL-C),apolipoprotein A1(Apo A1),and apolipoprotein B(Apo B),were detected.Two representative ratios,HDL-C-LDLC ratio(HLR)and Apo A1-Apo B ratio(ABR)were calculated.The relationship of these parameters with the prognosis of CRC patients including progression-free survival(PFS)and overall survival(OS)was analyzed by Kaplan-Meier plot and Cox proportional hazards regression.A novel lipoprotein cholesterol-apolipoprotein(LA)score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored.RESULTS Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C,Apo A1,HLR,and ABR were positively associated with the prognosis of CRC patients.LA score was independently associated with a good prognosis in resectable CRC patients.Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores.CONCLUSION The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.

结直肠癌组织中核受体视黄酸X受体a及核受体相互作用蛋白1的表达与预后的关系

目的分析结直肠癌组织中核受体视黄酸X受体a(RXRA)、核受体相互作用蛋白1(NRIP1)表达与患者临床病理特征、预后的关系。方法将2018年8月—2020年8月本院收治的106例结直肠癌患者手术过程中取得的癌组织标本纳入结直肠癌组(n=106),对应癌旁组织标本纳入癌旁组(n=106)。应用免疫组化法检测RXRA、NRIP1表达情况。采用多因素Cox回归分析探讨RXRA、NRIP1表达对结直肠癌患者预后的影响。结果结直肠癌组RXRA、NRIP1的阳性表达率分别为66.04%、69.81%,高于癌旁组的33.96%、30.19%,差异均有统计学意义(P<0.05)。病理分期为Ⅲ期、低分化、有浆膜浸润、有淋巴结转移患者的RXRA阳性表达率、NRIP1阳性表达率高于病理分期为Ⅱ期、中高分化、无浆膜浸润、无淋巴结转移患者,差异有统计学意义(P<0.05)。病理分期为Ⅱ期、低分化、无浆膜浸润、无淋巴结转移、RXRA阴性、NRIP1阴性患者的3年总生存率高于病理分期为Ⅲ期、中高分化、有浆膜浸润、有淋巴结转移、RXRA阳性、NRIP1阳性患者,差异有统计学意义(P<0.05)。多因素Cox回归分析显示,有浆膜浸润(HR=2.687,95%CI:1.531~3.156)、RXRA阳性(HR=3.743,95%CI:2.217~5.992)和NRIP1阳性(HR=2.641,95%CI:1.124~4.757)是结直肠癌患者预后的影响因素(P<0.05)。结论RXRA、NRIP1在结直肠癌中呈高表达,与肿瘤分期、分化及转移密切相关,可作为辅助评估患者预后的生物标记物。

结直肠癌组织中DJ-1表达对患者区域淋巴结转移及预后的临床意义

目的 分析结直肠癌(CRC)组织中蛋白/核酸去糖酶1(DJ-1)表达与患者区域淋巴结转移(LNM)及预后的相关性。方法 选择2017年6月至2022年4月在桂林市人民医院接受根治性手术的258例CRC患者作为研究对象,收集了258例患者的CRC组织,其中81例患者有配对的癌旁组织。另选择同期经内镜下治疗的58例患者的结直肠腺瘤组织作为对照。分析CRC组织中不同DJ-1蛋白表达与患者临床病理特征的关系。采用免疫组织化学法分析组织中DJ-1表达情况。采用多因素logistic回归分析探讨区域LNM的预测因素。采用单因素和多因素Cox回归分析探讨影响CRC患者复发及死亡的因素。采用Kaplan-Meier生存曲线分析不同DJ-1表达患者的5年无复发生存率和生存率。结果 3组的DJ-1蛋白表达差异有统计学意义(χ^(2)=202.557,P<0.001)。CRC组织中DJ-1蛋白中度表达和强表达患者的占比均显著高于癌旁组织和结直肠腺瘤组织(P均<0.05)。高表达组患者的年龄偏大,55.56%患者的原发病灶位于左半结肠,低分化CRC患者的占比较高,患者的区域LNM阳性率也较高(P均<0.05)。多因素logistic回归分析结果显示,CRC组织中DJ-1蛋白高表达能独立预测区域LNM和低分化CRC(P均<0.05)。258例患者的5年无复发生存率和生存率分别67.44%和70.54%。单因素和多因素Cox回归分析结果显示,CRC组织中DJ-1蛋白高表达为CRC患者复发和死亡的独立危险因素(P均<0.05)。上述结果与基于Oncomine数据库和TCGA队列的生物信息学分析结果基本一致。结论 CRC组织中DJ-1蛋白高表达与区域LNM相关,这可能是患者预后的影响因素。DJ-1有潜力成为预测CRC患者区域LNM和预后的生物标志物。