AmisChemotherapy-induced hepatotoxicity (CIH) is a significant concern in colorectal cancer (CRC) patients treated with the CAPEOX (capecitabine and oxaliplatin) regimen. Identifying predictive factors for CIH is crucial for clinical management.Patients and MethodsThis study analyzed colorectal tissue (CRT), plasma, and urine samples from CRC patients. Differentially expressed metabolites (DEMs) across these tissues were integrated for multi-omics analysis, and predictive models for CIH susceptibility were developed. An independent set of 75 plasma samples was used for validation.ResultsA total of 492 differentially expressed compounds were identified in samples from 63 CRC patients, including 105, 149, and 238 DEMs in CRT, plasma, and urine, respectively. Lipids and lipid-like molecules were predominant in all samples. Among these, urine samples exhibited the highest variability and provided the strongest predictive power for CIH susceptibility. Principal component analysis (PCA) effectively differentiated normal patients from those with CIH. The study revealed steatosis as the primary pathological feature of CIH, with disrupted lipid metabolism emerging as a key characteristic. Predictive models constructed from multi-tissue metabolites profile exhibited high accuracy, with the plasma model achieving an AUC of 0.933 in external validation set. Our study underscores the importance of individual metabolic variations in CIH susceptibility, reflecting the complex interplay of genetic, environmental, and lifestyle factors.ConclusionThis study emphasizes the critical role of alterations in lipid, polyamine, and purine metabolism, as well as impaired tissue repair mechanisms, were identified as key endogenous factors underlying CIH susceptibility. The developed predictive models demonstrate potential for clinical application in assessing CIH risk in CRC patients undergoing CAPEOX chemotherapy.

Colorectal cancer (CRC) is becoming increasingly prevalent worldwide. Fluoropyrimidine drugs are the primary chemotherapy regimens in routine clinical practice of CRC. However, the survival rate of patients on fluoropyrimidine-based chemotherapy varies significantly among individuals. Biomarkers of fluoropyrimidine drugs'' efficacy are needed to implement personalized medicine. This review summarized fluoropyrimidine drug-related microRNA (miRNA) by affecting metabolic enzymes or showing the relevance of drug efficacy. We first outlined 42 miRNAs that may affect the metabolism of fluoropyrimidine drugs. Subsequently, we filtered another 41 miRNAs related to the efficacy of fluoropyrimidine drugs based on clinical trials. Bioinformatics analysis showed that most well-established miRNA biomarkers were significantly enriched in the cancer pathways instead of the fluoropyrimidine drug metabolism pathways. The result also suggests that the miRNAs screened from metastasis patients have a more critical role in cancer development than those from non-metastasis patients. There are five miRNAs shared between these two lists. The miR-21, miR-215, and miR-218 can suppress fluoropyrimidine drugs'' catabolism. The miR-326 and miR-328 can reduce the efflux of fluoropyrimidine drugs. These five miRNAs could jointly act by increasing intracellular levels of fluoropyrimidine drugs'' cytotoxic metabolites, leading to better chemotherapy responses. In conclusion, we demonstrated that the dynamic changes in the transcriptional regulation via miRNAs might play significant roles in the efficacy and toxicity of the fluoropyrimidine drug. The reported miRNA biomarkers would help evaluate the efficacy of fluoropyrimidine drug-based chemotherapy and improve the prognosis of colorectal cancer patients.

Background: Chemotherapy-induced adverse effects (CIAEs) remain a challenging problem due to their high incidences and negative impacts on treatment in Chinese colorectal cancer (CRC) patients. We aimed to identify risk factors and predictive markers for CIAEs using food/nutrition data in CRC patients receiving post-operative capecitabine-based chemotherapy. Methods: Food/nutrition data from 130 Chinese CRC patients were analyzed. Univariate and multivariate analyses were used to identify CIAE-related food/nutrition factors. Prediction models were constructed based on the combination of these factors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the discrimination ability of models. Results: A total of 20 food/nutrition factors associated with CIAEs were identified in the univariate analysis after adjustments for total energy and potential confounding factors. Based on multivariate analysis, we found that, among these factors, dessert, eggs, poultry, and milk were associated with several CIAEs. Most importantly, poultry was an overall protective factor; milk and egg were risk factors for hand-foot syndrome (HFS) and bone marrow suppression (BMS), respectively. Developed multivariate models in predicting grade 1 to 3 CIAEs and grade 2/3 CIAEs both had good discrimination (AUROC values from 0.671 to 0.778, 0.750 to 0.946 respectively), which had potential clinical application value in the early prediction of CIAEs, especially for more severe CIAEs. Conclusions: Our findings suggest that patients with high milk and egg intakes should be clinically instructed to control their corresponding dietary intake to reduce the likelihood of developing HFS and BMS during capecitabine-based chemotherapy, respectively. Trial registration: ClinicalTrials.gov Identifier: NCT03030508.

The XELOX chemotherapy protocol that includes capecitabine and oxaliplatin is the routine treatment for colorectal cancer (CRC), but it can cause chemotherapy-related adverse events such as thrombocytopenia (TCP). To identify predictive biomarkers and clarify the mechanism of TCP susceptibility, we conducted integrative analysis using normal colorectal tissue (CRT), plasma, and urine samples collected before CRC patients received adjuvant XELOX chemotherapy. RNA-sequencing and DNA methylation arrays were performed on CRT samples, while liquid chromatography-mass spectrometry was performed on CRT, plasma, and urine samples. Differentially expressed features (DEFs) from each uni-omics analysis were then subjected to integrative analysis using Multi-Omics Factor Analysis (MOFA). Choline-deficiency in plasma and CRT was found as the most critical TCPrelated feature. Based on bioinformatic analysis and literature research, we further concluded that cholinedeficiency was the possible reason for most of the other TCP-related multi-omics DEFs, including metabolites representing reduced sphingolipid de novo synthesis and elevated solute carrier-mediated transmembrane transportation in CRT and plasma, DNA hypermethylation and elevated expression of genes involved in neuronal system genes. In terms of thrombocytopoiesis, these TCP-related DEFs may cause atypical maintenance and differentiation of megakaryocyte, resulting a suppressed ability of thrombocytopoiesis, making patients more susceptible to chemotherapy-induced TCP. At last, prediction models were developed and validated with reasonably good discrimination. The area under curves (AUCs) of training sets were all > 0.9, while validation sets had AUCs between 0.778 and 0.926. In conclusion, our results produced reliable marker systems for predicting TCP and promising target for developing precision treatment to prevent TCP.

目的:从结直肠癌(CRC)患者尿液中的内源性代谢物,寻找潜在的诊断生物标志物和卡培他滨相关不良反应(CRAE)的生物标志物.方法:采用超高效液相色谱结合四极杆飞行时间质谱(UHPLC-Q-TOF-MS)的方法,分析148例CRC患者和50例非肿瘤对照者的尿液代谢谱.对数据进行生物信息学分析并建立CRC预测模型.结果:CRC潜在诊断标志物包括3-Hexenedio-ic acid、Salicylic acid、(R)-Athanagrandione、PC(15:0/20:4)和(9E,11E)-Octadecadienoic等与脂类代谢相关的非极性代谢物.ROC曲线显示训练集的曲线下面积(area under curve,AUC)为0.980(95％CI:0.949-0.999),敏感度98.4％,特异度92.6％;测试集的AUC为1(95％CI:1-1),敏感度98.6％,特异度100％.(R)-Athanagrandione和Salicylic acid联合预测腹泻时,AUC为0.773(95％CI:0.617-0.921),敏感度为83.3％,特异度为68.2％.结论:尿液中非极性代谢标志物模型在CRC的早期诊断和CRAE的预测方面具有较高的临床价值.

To determine risk factors and develop novel prediction models for chemotherapy-induced adverse effects (CIAEs) in Chinese colorectal cancer (CRC) patients receiving capecitabine. A total of 233 Chinese CRC patients receiving post-operative chemotherapy with capecitabine were randomly divided into a training set (70%) and a validation set (30%). CIAE-related hematological/body parameters were screened by univariate logistic regression. Based on a set of factors selected from LASSO (least absolute shrinkage and selection operator) logistic regression, stepwise multivariate logistic regression was applied to develop prediction models. Area under the receiver operating characteristic (ROC) curve and Hosmer–Lemeshow (HL) test were used to evaluate the discriminatory ability and the goodness of fit of each model. In total, 35 variables were identified to be associated with CIAEs in univariate analysis. Developed multivariable models had AUCs (area under curve) ranging from 0.625 to 0.888 and 0.428 to 0.760 in the training and validation set, respectively. The grade ≥ 1 anemia multivariable model achieved the best discriminatory ability with AUC of 0.760 (95%CI: 0.609–0.912) and good calibration with HL P value of 0.450. Then, a nomogram was constructed to predict grade ≥ 1 anemia, which included variables of age, pre-operative hemoglobin count, and pre-operative albumin count, with C-indexes of 0.775 and 0.806 in the training and validation set, respectively. This study identified valuable hematological/body parameters related to CIAEs. A nomogram based on the multivariable model including three hematological/body predictors can accurately predict grade ≥ 1 anemia, facilitating clinicians to implement personalized medicine early for Chinese CRC patients receiving post-operative chemotherapy for better safety treatment. Trial registration This study was registered as a clinical trial at www.clinicaltrials.gov (NCT03030508).

Colorectal cancer (CRC) remains a major concern with high morbidity and mortality worldwide. Despite the positive influence of chemotherapy on the decline in CRC mortality, the negative influence of chemotherapyrelated adverse effects (CRAEs) caused by capecitabine (Cap) remains a challenging problem. DNA methylation alteration plays a pivotal role in gene expression regulation. Here, we aimed to screen reliable and novel biomarkers for CRC diagnosis and CRAE prediction using the advanced Illumina Infinium MethylationEPIC (850 K) BeadChip. Paired tumor and normal tissues from 21 Chinese CRC patients who received Cap-based adjuvant chemotherapy were analyzed. CRC-related methylation was characterized by hypermethylated promoter islands and hypomethylated intragenic openseas; CRAE-related methylation was characterized by hyper- (or hypo-) methylated intragenic (or intergenic) regions. Based on three types of methylation profiles (differentially methylated probes, differentially methylated regions, and gene-function-differentially methylated regions), pathway enrichment analyses revealed that CRC-related genes were significantly enriched in the neuronal system, metabolism of RNA, and extracellular matrix organization; CRAE-related genes were abundantly enriched in pathways controlling regeneration functions and immune response. Finally, based on genes within the mostly related pathways and LASSO logistic regression selection, the integrated-methylation-marker systems developed here demonstrated high discriminative accuracy in both CRC diagnosis (AUROC = 1) and CRAE prediction (AUROC = 0.817-1). In conclusion, we conducted a comprehensive DNA methylation analysis of CRC patients with chemotherapy, which provided new insights into the formation of CRC and CRAEs. Most importantly, our findings identified potentially CRAE-related metabolic pathways and markers, providing a valuable reference for personalized medicine promising better safety.

Primary pelvic solitary fibrous tumor(SFT) with surrounding viscera invasion is rare. The present case reported a case of pelvic huge solitary fibrous tumor with rectum and retroperitoneum invasion, and we also described its imaging findings and surgical procedures in detail. The differential diagnosis of the disease based on immunohistochemistry and molecular pathology was further discussed.

Hand-foot syndrome (HFS) is a common capecitabine-based chemotherapy-related adverse event (CRAE) in patients with colorectal cancer (CRC). It is of great significance to comprehensively identify susceptible factors for HFS, and further to elucidate the biomolecular mechanism of HFS susceptibility. We performed an untargeted multi-omics analysis integrating DNA methylation, transcriptome, and metabolome data of 63 Chinese CRC patients who had complete CRAE records during capecitabine-based chemotherapy. We found that the metabolome changes for each of matched plasma, urine, and normal colorectal tissue (CRT) in relation to HFS were characterized by chronic tissue damage, which was indicated by reduced nucleotide salvage, elevated spermine level, and increased production of endogenous cytotoxic metabolites. HFS-related transcriptome changes of CRT showed an overall suppressed inflammation profile but increased M2 macrophage polarization. HFS-related DNA methylation of CRT presented gene-specific hypermethylation on genes mainly for collagen formation. The hypermethylation was accumulated in the opensea and shore regions, which elicited a positive effect on gene expression. Additionally, we developed and validated models combining relevant biomarkers showing reasonably good discrimination performance with the area under the receiver operating characteristic curve values from 0.833 to 0.955. Our results demonstrated that the multi-omics variations associated with a profibrotic phenotype were closely related to HFS susceptibility. HFS-related biomolecular variations in CRT contributed more to the relevant biomolecular mechanism of HFS than in plasma and urine. Spermine-related DNA hypermethylation and elevated expression of genes for collagen formation were closely associated with HFS susceptibility. These findings provided new insights into the susceptible factors for chemotherapy-induced HFS, which can promote the implementation of individualized treatment against HFS.

结直肠癌是世界第三大常见肿瘤和第二大癌症死亡原因,晚期CRC患者占有很大的比例.对于局部晚期结直肠癌,特别是侵犯到相邻脏器的患者,结直肠癌多脏期联合切除手术是唯一的根治方法,此类手术往往因手术界限不清、肿瘤巨大而具有一定的困难.本文分析了我院1例左半结肠癌侵犯胰尾、脾、胃和膈肌的病例,并对腹腔镜下多脏器联合切除手术的优点和缺点进行分析,以期为局部晚期结直肠癌的治疗提供参考.

Background: Metabolomics has demonstrated its potential in the early diagnosis, drug safety evaluation and personalized toxicology research of various cancers. Objectives:We aim to screen for potential diagnostic and capecitabine-related adverse effect (CRAE) biomarkers from urinary endogenous metabolites in Chinese colorectal cancer (CRC) patients.Methods: The metabolic profiles of 139 CRC patients and 50 non-neoplastic controls were analyzed using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry.Results: There were 41 metabolites identified between the CRC patients and the non-neoplastic controls, and 19 metabolites were identified between CRC patients with and without CRAE.Based on these identified metabolites, bioinformatic analysis and prediction model construction were completed.Most of these differential metabolites have important roles in cell proliferation and differentiation and the immune system.Based on binary logistic regression, a CRC prediction model, composed of 3-methylhistidine, N-heptanoylglycine, N 1 ,N 12 -diacetylspermine and hippurate, was established, with an area under curve (AUC) of 0.980 (95% CI: 0.953-1.000;sensitivity: 94.3%; specificity: 92.0%) in the training set, and an AUC of 0.968 (95% CI: 0.933-1.000;sensitivity: 89.9%; specificity: 92.0%) in the testing set.In addition, methionine and 4-pyridoxic acid can be combined to predict hand foot syndrome, with an AUC of 0.884; ubiquinone-1 and 4-pyridoxic acid can be combined to predict anemia, with an AUC of 0.889; and 5-acetamidovalerate and 3,4-methylenesebacic acid can be combined to predict neutropenia, with an AUC of 0.882. Conclusion:The profiling of urine polar metabolites has great potential in the early detection of CRC and the prediction of CRAE.

我国结直肠癌发病率和死亡率居高不下,直肠癌的发病率与术后局部复发率(LRR)通常高于结肠癌,且手术难度高.目前为了防止直肠癌的局部复发大多采取多学科方法医治.新辅助放化疗(nCRT)作为一种发展中的多学科方法,可提高治愈率又可维持器官功能,在直肠癌治疗中起着至关重要的作用.本综述旨在阐明nCRT的现状与未来的改进方向.

Objective To explore the independent risk factors of postoperative anastomotic leakage (AL) in patients with colorectal cancer. Methods Retrospectively analyze the data of 926 patients with colorectal cancer who received surgery in the Department of Surgery, Shanghai Changzheng Hospital from Dec 2010 to Apr 2014. Through case-control analysis and chi-square test, the risk factors of AL were screened in the variables of clinicopathological classification. Multivariate analysis was used by logistic regression to screen independent risk factors. Results Hypertension, laparoscopy surgery and non-defunctioning stoma were independent risk factors for AL in overall samples (OR=1.907, 2.252, 5.556; P=0.016, 0.006, 0.001, respectively). Subgroup analysis showed that left colon was a risk factor of AL in colon cancer subgroup (OR=2.519, P=0.032). Hypertension, laparoscopic and non-defunctioning stoma were independent risk factors in rectal cancer subgroup (OR=2.597, 7.609, 9.346; P=0.012, 0.007, <0.001, respectively). Hypertension, non-defunctioning stoma and bleeding ≥ 400 mL were independent risk factors in laparoscopic subgroup (OR=2.407, 5.376, 3.922; P=0.006, 0.002, 0.001, respectively). Hypertension, laparoscopy surgery and rectal cancer were independent risk factors in non-defunctioning stoma subgroup (OR=1.969, 1.859, 1.716; P=0.015, 0.046, 0.059, respectively). Hypertension, laparoscopy surgery and operative time≥ 3 h were independent risk factors in rectal cancer patients with non-defunctioning stoma subgroup (OR=2.796, 7.346, 2.287; P=0.012, 0.008, 0.046, respectively). Conclusion For rectal cancer patients with hypertension, laparoscopic and non-defunctioning stoma, close attention should be paid and targeted prevention are needed to reduce the occurrence of postoperative AL. Key words: Colorectal neoplasms; Postoperative complications; Risk factors; ASA score

人类白细胞抗原G(Human Leucocyte Antigen-G,HLA-G)是一种非典型性的MHC-I类分子.根据研究数据显示,HLA-G具有免疫细胞的功能,与肿瘤、生殖以及器官移植等免疫有关,可以抑制自然杀伤细胞和细胞毒性T淋巴细胞,参与母胎免疫耐受的形成.由于HLA-G能通过抑制自然杀伤细胞,达到诱导肿瘤抗原特异性T细胞消亡等的特性,目前已成为肿瘤癌症治疗领域的研究重点.在临床上建立一种非侵袭性、简单而有效的血清学方法用于对结直肠癌的诊断、良性和恶性肠道疾病的有效区分以及结直肠癌的治疗有重要的意义.本文针对HLA-G在结直肠癌的诊断以及预后中的作用进行研究分析,并对其临床效果进行评估.

结直肠癌是临床较常见的恶性肿瘤之一,给社会带来沉重的负担.卡培他滨是口服氟尿嘧啶类前体药物,用于多种恶性肿瘤的化疗.化疗中,原发性和继发性耐药仍然较为普遍,且个体差异大,因剂量限制性毒性而导致的延迟给药和降低剂量,影响了生存预后.当前,随着精准医疗的发展,许多卡培他滨毒效和疗效的标志物被发现.近年来有关卡培他滨治疗结直肠癌的毒效标志物主要有临床病理指标、代谢酶表达、基因多态、表观遗传学和代谢组学的预测指标.分析表明单一指标的预测准确度不高,而联合各类预测指标建立的模型有可能显著提高毒效预测的准确度.

The human trophoblast cell surface antigen 2 (TROP2) is overexpressed in many cancers. However, its effect on proliferation, migration and metastasis of gallbladder cancer remains unclear. In this study, we found that TROP2 was highly expressed in gallbladder cancer. Overexpression of TROP2 was associated with poor prognosis. Knockdown of TROP2 in gallbladder cancer cell lines strongly inhibited the cell proliferation, clone formation, invasion and migration in vitro, while TROP2 overexpression had opposite effects. In addition, knockdown of TROP2 increased the expression of total PTEN, p-PTEN and PDK-1 but reduced p-AKT via PI3K/AKT pathway. TROP2 downregulation also inhibited vimentin and increased E-cadherin expression during epithelial-mesenchymal transition (EMT). Moreover, gallbladder cancer cells with TROP2 knockdown formed smaller xenografted tumors in vivo. In consistent with in vitro results, TROP2 inhibition decreased Akt phosphorylation, increased PTEN expression and postponed EMT of gallbladder cancer cells in vivo. In conclusion, we revealed that TROP2 promoted the proliferation, migration and metastasis of gallbladder cancer cells by regulating PI3K/AKT pathway and inducing EMT. TROP2 could serve as a potential prognostic biomarker and therapeutic target for the clinical management of gallbladder cancer.

目的:探讨癌胚抗原(carcinoembryonic antigen,CEA)、癌抗原19-9 (cancer antigen 19-9,CA19-9)、癌抗原125 (cancer antigen 125,CA125)和粪便隐血等一系列术前实验室指标联合检验对结直肠癌(colorectal cancer,CRC)的诊断价值,以及它们与炎性指标联合预测结直肠癌患者对辅助化疗的不良反应的临床价值.方法:收集上海长征医院2011年1月-2014年4月行手术治疗的859例CRC患者的回顾性临床数据,和2016年6月-2017年6月行手术治疗的251例CRC患者的前瞻性临床数据,以及TCGA数据库中617例CRC患者的临床资料.x2检验分析影响CRC患者中CEA、CA19-9、CA125和粪便隐血假阴性率的临床病理因素,以及这些指标联合检验的诊断价值.Spearman秩相关检验分析前瞻性数据中接受术后卡培他滨方案辅助化疗的108例患者的术前肿瘤标志物、粪便隐血、炎性指标与化疗不良反应的相关性,并用受试者工作特征(receiver operating characteristic,ROC)曲线分析各项指标预测不良反应的潜在价值.结果:CEA、CA19-9和CA125用于诊断CRC的假阴性率主要受肿瘤病理分期影响(P值均＜0.05),而粪便隐血用于诊断CRC的假阴性率不受病理分期影响(P＞0.05);另外,各指标单项检测用于诊断CRC的假阴性率均高于43.7％,而联合检验可降低假阴性率至18.9％ (P＜0.001).术前血小板-淋巴细胞比值(platelet to lymphocyte ratio,PLR)升高可预测化疗后手足综合征,术前血小板计数减少可预测化疗后血小板缺乏,血红蛋白和白蛋白水平降低可预测贫血,粒细胞和单核细胞计数减少可预测粒细胞缺乏,而粒细胞计数减少则对预测3～4级整体骨髓抑制具有潜在作用[曲线下面积(area under curve,AUC)均＞0.6,P值均＜0.05].结论:CEA、CA19-9、CA125与粪便隐血联合检验可提高诊断CRC的敏感性,降低假阴性率.术前PLR升高具有预测手足综合征的潜在价值,而术前血细胞计数减少具有预测骨髓抑制的潜在价值;因此,这2个检验指标值得进一步研究.

ObjectiveTo explore the survival of different stage of patients with colorectal cancer, and evaluate the clinicopathologic factors associated with prognosis.MethodsThe SEER*Stat software was used to identify patients whose pathological diagnosis as colorectal malignancy from 2004 to 2009, and underwent surgical treatment. Univariate and Cox multivariate regression analysis were applied to evaluate the prognostic factors. The Kaplan-Meier method was used to calculate the cumulative survival rate, and the significant difference was evaluated by the log-rank test.ResultsThe mean survival time of 1 829 colorectal cancer patients was (76.71±0.16) months, the median survival time was 98 months and the overall 5-year survival was 60.4%. The 5-year survival rates of the stageⅠ,Ⅱ,Ⅲ,Ⅳ patients were 81.2%, 71.7%, 58.4%, 14.4%, and the relationship between the overall survival was stageⅠ> stageⅡ> stageⅢ> stageⅣ (χ2=26 063.383;P<0.001). But, the overall survival of stageⅡwas located between stageⅢA andⅢB. The overall 5-year survival of stageⅢA (78.7%) andⅠB (79%) was almost (χ2=0.040;P=0.841), and better thanⅡA (χ2=39.409;P<0.001),ⅡB (χ2=212.271;P<0.001),ⅡC (χ2=307.720;P<0.001). The overall 5-year survival of stageⅢB (61.5%) was better than stageⅡB (60.1%) (χ2=4.366;P=0.037) andⅡC (54.6%) (χ2=33.047;P<0.001), but worse than stageⅡA (73.6%) (χ2=692.563;P<0.001). The factors of sex (χ2=5.662;P=0.017), years of diagnosis (χ2=100.476;P<0.001), race (χ2=227.960;P<0.001), primary site (χ2=457.809;P<0.001), pathological grading (χ2=2 364.001;P<0.001), adjacent organ involvement (χ2=3 475.630;P<0.001), depth of invasion (χ2=8 281.813;P<0.001), lymph node metastasis (χ2=12 034.484;P<0.001), total number of lymph nodes (χ2=362.497;P<0.001) and metastasis (χ2=23 960.974;P<0.001) influenced the survival rate by univariate analysis. The factors of sex (95%CI: 0.958~0.997;P=0.025), years of diagnosis (95%CI: 0.967~0.992;P=0.001), race (95%CI: 0.912~0.942;P<0.001), Primary site (95%CI: 0.896~0.912;P<0.001), Pathological grading (95%CI: 1.162~1.204;P<0.001), adjacent organ involvement (95%CI: 0.758~0.832;P<0.001), depth of invasion (95%CI: 1.360~1.407;P<0.001), lymph node metastasis (95%CI:1.302~1.329;P<0.001), total number of lymph nodes (95%CI: 0.667~0.696;P<0.001) and metastasis (95%CI: 3.055~3.211;P<0.001) were available independent prognostic factors through multivariate analysis.ConclusionsWith the increase of TNM stage, the overall survival rate of patients with colorectal cancer undergoing radical surgery was gradually reduced. However, compared the prognosis ofⅡA、ⅡB、ⅡC with that ofⅢA、ⅢB, primary tumor invasion depth (T grading) may be more important than the number of lymph node metastasis (N grading) in predicting the prognostic value. In addition, the factors of sex, years of diagnosis, race, primary site, pathological grading, adjacent organ involvement, depth of invasion, lymph node metastasis, total number of lymph nodes and metastasis were available independent prognostic factors. This provided reference for the analysis of the prognosis of patients with colorectal cancer.

Objective To investigate the expression of human trophoblast cell-surface antigen 2 (TROP2),phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2),and cyclin D1 in gallbladder carcinoma tissue and their correlation with clinicopathological parameters,as well as their association with the prognosis of patients with gallbladder carcinoma.Methods A total of 88 patients who were diagnosed with gallbladder carcinoma in Changzheng Hospital,Second Military Medical University,from June 2005 to June 2010 were enrolled,and their pathological specimens were obtained.Immunohistochemistry was used to measure the expression of TROP2,p-ERK1/2,and cyclin D1 in 88 gallbladder carcinoma tissue samples and 15 adjacent tissue samples.The chi-square test was used for comparison of categorical data between groups,and the Spearman method was used to investigate the correlation between any two parameters of TROP2,p-ERK1/2,and cyclin D1;univariate and multivariate Cox regression analyses were used to analyze the influencing factors for the prognosis of patients with gallbladder carcinoma;the Kaplan-Meier method was used to plot their survival curves.Results The positive rates of TROP2,p-ERK1/2,and cyclin D1 in gallbladder cancer tissue were 74.30％,58.40％,and 55.30％,respectively,significantly higher than those in adjacent tissue (5.42％,35.67％ and 39.87％,respectively) (P ＜ 0.05).The expression of TROP2,p-ERK1/2,and cyclin D1 was associated with gallstones,tumor diameter,degree of tumor differentiation,vascular and perineural invasion,lymph node metastasis,surgical procedure,and TNM stage (x2 =4.300 ～ 53.315,all P ＜ 0.05).The expression of TROP2 was positively correlated with that of p-ERK1/2 and cyclin D1 (rs =0.402 and 0.742,both P ＜ 0.001),and the expression of p-ERK1/2 was also positively correlated with that of cyclin D1 (rs =0.242,P =0.023).The multivariate survival analysis showed that positive expression of TROP2 had a significant influence on 3-year survival rate (RR =2.412,95％ CI:1.186 ～5.126,P =0.010).Conclusion High expression of TROP2 may be an important reason for malignant progression of gallbladder carcinoma,and highly expressed TROP2 may mediate the high expression of p-ERK1/2 and cyclin D1,resulting in the malignant progression of gallbladder carcinoma.Positive expression of TROP2 is an independent risk factor for the prognosis of patients with gallbladder carcinoma and may be an effective target for clinical intervention.

objective To explore the relationship and clinical significance of human trophoblast cell-surface antigen 2 (TROP2), phosphatase and tensin homolog (PTEN), phosphorylated protein kinase B (p-AKT) in gall-bladder carcinoma. Methods A tatal of 71 patients with gallbladder carcinoma in our hospital were selected be-tween Jan. 2003 and Dec. 2009. Immunohistochemical staining method was used to detected the protein expres-sion of TROP2, PTEN and p-AKT in 71 cases of gallbladder carcinoma tissues and 15 cases of tumor adjacent tissues, Pearson chi-square test was used to analyze the relationship between the protein expression of TROP2, PTEN, p-AKT and the clinical pathological parameters, Spearman test was used to detect the relationship among TROP2, PTEN and p-AKT. Results (1)Compared with the tumor adjacent tissues, the protein expression of TROP2 and p-AKT in gallbladder carcinoma tissues were significantly increased (P<0.05), while the protein ex-pression of PTEN in gallbladder carcinoma tissues was significantly decreased (P<0.05); (2)The proteins expres-sion of TROP2, PTEN and p-AKT were independent with the gender and age (P>0.05), but which was correlated with gallstones, tumor differentiation, organ invasion, depth of invasion and TNM stage (P<0.05); (3)The protein expression of TROP2 was positively correlated with p-AKT (P<0.05), but which was negatively corelated with PTen (P<0.05). Conclusion Abnormal activation of TROP2/PTEN/p-AKT signal pathway may play an impor-tant role in malignant progression of gallbladder carcinoma, the mechanism may be related to TROP2 negative regulation of PTEN expression, inhibiting its dephosphorylation, resulting in increased expression of p-AKT, and promoting the proliferation and metastasis of gallbladder cancer cells. It is an important cause for malignant pro-gression of gallbladder carcinoma, which provides a theoretical basis for clinical targeted intervention studies.