Risk factors for lymph node metastasis in superficial esophageal squamous cell carcinoma

In this editorial,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.We focused on identifying risk factors for lymph node metastasis(LNM)in superficial esophageal squamous cell carcinoma(SESCC)patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients,thereby helping to guide the selection of an appropriate treatment plan.The current standard treatment for SESCC is radical esophagectomy with lymph node dissection.However,esophagectomy is associated with considerable morbidity and mortality.Endoscopic resection(ER)offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome.However,since ER is a localized treatment that does not allow for lymph node dissection,the risk of LNM in SESCC limits the effectiveness of ER.Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy.Previous studies have shown that tumor size,macroscopic type of tumor,degree of differentiation,depth of tumor invasion,and lymphovascular invasion are factors associated with LNM in patients with SESCC.In addition,tumor budding is commonly associated with LNM,recurrence,and distant metastasis,but this topic has been less covered in previous studies.By comprehensively evaluating the above risk factors for LNM,useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.

Analysis of clinicopathological features and prognostic factors of breast cancer brain metastasis

BACKGROUND Breast cancer(BC)has become the most common malignancy in women.The incidence and detection rates of BC brain metastasis(BCBM)have increased with the progress of imaging,multidisciplinary treatment techniques and the extension of survival time of BC patients.BM seriously affects the quality of life and survival prognosis of BC patients.Therefore,clinical research on the clinicopathological features and prognostic factors of BCBM is valuable.By analyzing the clinicopathological parameters of BCBM patients,and assessing the risk factors and prognostic indicators,we can perform hierarchical diagnosis and treatment on the high-risk population of BCBM,and achieve clinical benefits of early diagnosis and treatment.AIM To explore the clinicopathological features and prognostic factors of BCBM,and provide references for diagnosis,treatment and management of BCBM.METHODS The clinicopathological data of 68 BCBM patients admitted to the Air Force Medical Center,Chinese People’s Liberation Army(formerly Air Force General Hospital)from 2000 to 2022 were collected.Another 136 BC patients without BM were matched at a ratio of 1:2 based on the age and site of onset for retrospective analysis.Categorical data were subjected to χ^(2) test or Fisher’s exact probability test,and the variables with P<0.05 in the univariate Cox proportional hazards model were incorporated into the multivariate model to identify high-risk factors and independent prognostic factors of BCBM,with a hazard ratio(HR)>1 suggesting poor prognostic factors.The survival time of patients was estimated by the Kaplan-Meier method,and overall survival was compared between groups by log-rank test.RESULTS Multivariate Cox regression analysis showed that patients with stage Ⅲ/Ⅳ tumor at initial diagnosis[HR:5.58,95% confidence interval(CI):1.99–15.68],lung metastasis(HR:24.18,95%CI:6.40-91.43),human epidermal growth factor receptor 2(HER2)-overexpressing BC and triple-negative BC were more prone to BM.As can be seen from the prognostic data,52 of the 68 BCBM patients had died by the end of follow-up,and the median time from diagnosis of BC to the occurrence of BM and from the occurrence of BM to death or last follow-up was 33.5 and 14 mo,respectively.It was confirmed by multivariate Cox regression analysis that patients with neurological symptoms(HR:1.923,95%CI:1.005-3.680),with bone metastasis(HR:2.011,95%CI:1.056-3.831),and BM of HER2-overexpressing and triple-negative BC had shorter survival time.CONCLUSION HER2-overexpressing,triple-negative BC,late tumor stage and lung metastasis are risk factors of BM.The presence of neurological symptoms,bone metastasis,and molecular type are influencing prognosis factors of BCBM.

Predicting lymph node metastasis in colorectal cancer:An analysis of influencing factors to develop a risk model

BACKGROUND Colorectal cancer(CRC)is a significant global health issue,and lymph node metastasis(LNM)is a crucial prognostic factor.Accurate prediction of LNM is essential for developing individualized treatment strategies for patients with CRC.However,the prediction of LNM is challenging and depends on various factors such as tumor histology,clinicopathological features,and molecular characteristics.The most reliable method to detect LNM is the histopathological examination of surgically resected specimens;however,this method is invasive,time-consuming,and subject to sampling errors and interobserver variability.AIM To analyze influencing factors and develop and validate a risk prediction model for LNM in CRC based on a large patient queue.METHODS This study retrospectively analyzed 300 patients who underwent CRC surgery at two Peking University Shenzhen hospitals between January and December 2021.A deep learning approach was used to extract features potentially associated with LNM from primary tumor histological images while a logistic regression model was employed to predict LNM in CRC using machine-learning-derived features and clinicopathological variables as predictors.RESULTS The prediction model constructed for LNM in CRC was based on a logistic regression framework that incorporated machine learning-extracted features and clinicopathological variables.The model achieved high accuracy(0.86),sensitivity(0.81),specificity(0.87),positive predictive value(0.66),negative predictive value(0.94),area under the curve for the receiver operating characteristic(0.91),and a low Brier score(0.10).The model showed good agreement between the observed and predicted probabilities of LNM across a range of risk thresholds,indicating good calibration and clinical utility.CONCLUSION The present study successfully developed and validated a potent and effective risk-prediction model for LNM in patients with CRC.This model utilizes machine-learning-derived features extracted from primary tumor histology and clinicopathological variables,demonstrating superior performance and clinical applicability compared to existing models.The study provides new insights into the potential of deep learning to extract valuable information from tumor histology,in turn,improving the prediction of LNM in CRC and facilitate risk stratification and decision-making in clinical practice.

Risk factors of lymph node metastasis in rectal neuroendocrine tumors

Objective The aim of this study was to investigate the risk factors of lymph node metastasis in rectal neuroendocrine neoplasms(RNENs).Methods We enrolled 168 patients with RNENs as the research object,and their clinicopathological and survival data were collected.The risk factors affecting lymph node metastasis were analyzed retrospectively,and independent risk factors affecting prognosis were evaluated.Results Analysis showed that age,tumor diameter,tumor function,grade,and T stage were correlated with lymph node metastasis(P<0.05).Multiple logistic regression analysis showed that tumor size,grade,and T stage were independent risk factors for lymph node metastasis in patients with RNENs.Kaplan-Meier analysis showed that the 5-year overall survival(OS)of patients with lymph node metastasis was 40.0%(10/25),and that of patients without lymph node metastasis was 93.0%(133/143).The prognosis of RNENs patients with lymph node metastasis along with patients with large tumor diameter and high grade was poor.Cox multivariate analysis showed that tumor diameter(HR=1.985,P=0.008),grade(HR=3.416,P=0.004),T stage(HR=2.413,P=0.014),and lymph node metastasis(HR=3.119,P=0.000)were independent risk factors affecting the prognosis of patients with RNENs.Conclusion Tumor size,grade,and T stage are the main risk factors for lymph node metastasis and prognosis in patients with RNENs.These risk factors should be fully evaluated before surgery.

P300/CBP-associated factor(PCAF)-mediated acetylation of Fascin at lysine 471 inhibits its actin-bundling activity and tumor metastasis in esophageal cancer

Background:Fascin is crucial for cancer cell filopodium formation and tumor metastasis,and is functionally regulated by post-translational modifications.However,whether and how Fascin is regulated by acetylation remains unclear.This study explored the regulation of Fascin acetylation and its corresponding roles in filopodium formation and tumor metastasis.Methods:Immunoprecipitation and glutathione-S-transferase pull-down assays were performed to examine the interaction between Fascin and acetyltransferase P300/CBP-associated factor(PCAF),and immunofluorescence was used to investigate their colocalization.An in vitro acetylation assay was performed to identify Fascin acetylation sites by using mass spectrometry.A specific antibody against acetylated Fascin was generated and used to detect the PCAF-mediated Fascin acetylation in esophageal squamous cell carcinoma(ESCC)cells using Western blotting by overexpressing and knocking down PCAF expression.An in vitro cell migration assay was performed,and a xenograft model was established to study in vivo tumor metastasis.Live-cell imaging and fluorescence recovery after photobleaching were used to evaluate the function and dynamics of acetylated Fascin in filopodium formation.The clinical significance of acetylated Fascin and PCAF in ESCC was evaluated using immunohistochemistry.Results:Fascin directly interacted and colocalized with PCAF in the cytoplasm and was acetylated at lysine 471(K471)by PCAF.Using the specific antiAcK471-Fascin antibody,Fascin was found to be acetylated in ESCC cells,and the acetylation level was consequently increased after PCAF overexpression and decreased after PCAF knockdown.Functionally,Fascin-K471 acetylation markedly suppressed in vitro ESCC cell migration and in vivo tumor metastasis,whereas Fascin-K471 deacetylation exhibited a potent oncogenic function.Moreover,Fascin-K471 acetylation reduced filopodial length and density,and lifespan of ESCC cells,while its deacetylation produced the opposite effect.In the filipodium shaft,K471-acetylated Fascin displayed rapid dynamic exchange,suggesting that it remained in its monomeric form owing to its weakened actinbundling activity.Clinically,high levels of AcK471-Fascin in ESCC tissues were strongly associated with prolonged overall survival and disease-free survival of ESCC patients.Conclusions:Fascin interacts directly with PCAF and is acetylated at lysine 471 in ESCC cells.Fascin-K471 acetylation suppressed ESCC cell migration and tumor metastasis by reducing filopodium formation through the impairment of its actin-bundling activity.

Risk factors for lymph node metastasis in patients with pancreatic neuroendocrine neoplasms

BACKGROUND Although PNENs generally have a better prognosis than pancreatic cancers,some PNENs display malignant behavior including lymph node(LN)metastasis.Complete tumor resection can be the only potentially curative treatment for patients with resectable PNENs.However,the indications for LN dissection are still controversial.Over the last decade,minimally invasive surgery such as laparoscopic pancreatic surgery(LPS)has been increasingly performed for pancreatic tumors including PNENs.AIM To investigate the risk factors for LN metastasis in PNENs and to select appropriate patients for limited surgery by LPS.METHODS From April 2001 to December 2019,92 patients underwent pancreatic resection for PNENs at Kumamoto University Hospital.Finally,82 patients were enrolled in this study.Using perioperative factors,we examined the predictive factors for LN metastasis in PNENs.RESULTS Among the 82 patients,the percentage of LN metastasis according to the pathological findings was 12%(10/82 cases).The median tumor size was 12 mm(range:5-90 mm).The median tumor size in the LN-positive group(37 mm)was significantly larger than that in the LN-negative group(12 mm)(P=0.0001).Multivariate analyses revealed that larger tumor size(≥20 mm)was an independent risk factor for LN metastasis(odds ratio 16.8,P=0.0062).In patients with small tumors(≤10 mm),LN metastasis was not found.CONCLUSION Larger tumor size(≥20 mm)is an independent risk factor for LN metastasis in PNENs.In smaller PNENs(≤10 mm),we may be able to choose limited surgery without LN dissection.

Sixth and seventh tumor-node-metastasis staging system compared in gastric cancer patients

AIM: To investigate the clinical relevance and prognosis regarding survival according to the changes of the tumor-node-metastasis(TNM) in gastric cancer patients. METHODS: We retrospectively studied 347 consecutive subjects who underwent surgery for gastric adenocarcinoma at the Division of General Surgery, Hospital of Busto Arsizio, Busto Arsizio, Italy between June 1998 and December 2009. Patients who underwent surgery without curative intent, patients with tumors of the gastric stump and patients with tumors involving the esophagus were excluded for survival analysis. Patients were staged according to the 6thand 7thedition TNM criteria; 5-year overall survival rates were investigated, and the event was defined as death from any cause. RESULTS: After exclusion, our study population included 241 resected patients with curative intent for gastric adenocarcinoma. The 5-year overall survival(5-year OS) rate of all the patients was 52.8%. Thediagnosed stage differed in 32% of 241 patients based on the TNM edition used for the diagnosis. The patients in stage Ⅱ according to the 6thedition who were reclassified as stage Ⅲ had significantly worse prognosis than patients classified as stage Ⅱ(5-year OS, 39% vs 71%). According to the 6thedition, 135 patients were classifed as T2, and 75% of these patients migrated to T3 and exhibited a significantly worse prognosis than those who remained T2, regardless of lymph node involvement(37% vs 71%). The new N1 patients exhibited a better prognosis than the previous N1 patients(67% vs 43%). CONCLUSION: 7thTNM allows new T2 and N1 patients to be selected with better prognosis, which leads to different staging. New stratification is important in multimodal therapy.

seventh tumor-node-metastasis staging of gastric cancer: Five-year follow-up

Seventh tumor-node-metastasis(TNM) classification for gastric cancer,published in 2010,introduced changes in all of its three parameters with the aim to increase its accuracy in prognostication. The aim of this review is to analyze the efficacy of these changes and their implication in clinical practice. We reviewed relevant Literature concerning staging systems in gastric cancer from 2010 up to March 2016. Adenocarcinoma of the esophago-gastric junction still remains a debated entity,due to its peculiar anatomical and histological situation: further improvement in its staging are required. Concerning distant metastases,positive peritoneal cytology has been adopted as a criterion to define metastatic disease: however,its search in clinical practice is still far from being routinely performed,as staging laparoscopy has not yet reached wide diffusion. Regarding definition of T and N: in the era of multimodal treatment these parameters should more influence both staging and surgery. The changes about T-staging suggested some modifications in clinical practice. Differently,many controversies on lymph node staging are still ongoing,with the proposal of alternative classification systems in order to minimize the extent of lymphadenectomy. The next TNM classification should take into account all of these aspects to improve its accuracy and the comparability of prognosis in patients from both Eastern and Western world.

剪接因子3B亚单位1在乳腺癌组织中的表达及与患者临床病理特征关系

目的:探讨剪接因子3B亚单位1(SF3B1)在乳腺癌组织中的表达及与患者临床病理特征的关系。方法:分析88例乳腺癌患者乳腺癌组织和癌旁组织SF3B1的表达水平,评估SF3B1对乳腺癌的诊断价值,比较SF3B1高表达组与低表达组临床病理特征差异。结果:乳腺癌组织SF3B1表达明显高于癌旁组织(P<0.05);SF3B1诊断乳腺癌的AUC为0.713;SF3B1诊断乳腺癌的最佳截断值为110.72。高表达组年龄明显高于低表达组,淋巴结转移为N 0的比例明显低于低表达组,两组病理学分级比较差异有统计学意义(P<0.05)。结论:SF3B1在乳腺癌组织中的表达明显上调,在诊断乳腺癌方面效能较好,与临床病理参数有关,可能参与了乳腺癌的发生、侵袭和转移过程的调控。

宫颈癌淋巴结转移患者PD-L1与TILs表达水平及其与预后的关系

目的探讨宫颈癌淋巴结转移患者程序性死亡配体-1(PD-L1)、肿瘤浸润淋巴细胞亚群(TILs)表达水平及其与患者预后的关系。方法选取2007年1月至2013年9月在梅州市人民医院诊治并接受宫颈癌根治性切除术后发生淋巴结转移的101例患者作为研究对象。采用免疫组织化学法检测PD-L1、CD4^(+)TILs、CD8^(+)TILs、叉头翼螺旋转录因子3(Foxp3)^(+)TILs表达水平。比较不同PD-L1表达水平患者临床病理特征差异;采用Spearman相关对PD-L1表达水平与TILs密度的相关性进行分析;采用Kaplan-Meier生存分析法分析PD-L1表达水平、TILs密度及密度比值与累计生存率的关系;采用Cox比例风险模型分析患者预后的独立影响因素。结果PD-L1表达于肿瘤细胞的细胞质和(或)细胞膜,阳性表达率为34.65%(35/101);CD4^(+)TILs计数为94(45,190);CD8^(+)TILs计数为63(31,117);FoxP3^(+)TILs计数为6.0(2.5,13.5);FoxP3^(+)TILs/CD8^(+)TILs比值为0.109(0.036,0.193)。PD-L1阳性表达组与PD-L1阴性表达组CD4^(+)TILs、CD8^(+)TILs、FoxP3^(+)TILs密度比较,差异均有统计学意义(P<0.05)。PD-L1表达情况与CD4^(+)TILs、CD8^(+)TILs、FoxP3^(+)TILs密度均呈正相关(r=0.305、0.222、0.222,P=0.002、0.026、0.026)。生存组与死亡组CD4^(+)TILs密度、CD8^(+)TILs密度和PD-L1表达情况比较,差异均有统计学意义(P<0.05)。手术年龄<50岁、PD-L1阳性表达、CD4^(+)TILs高密度、CD8^(+)TILs高密度、FoxP3^(+)TILs/CD8^(+)TILs低比值患者累计生存率均高于手术年龄≥50岁、PD-L1阴性表达、CD4^(+)TILs低密度、CD8^(+)TILs低密度、FoxP3^(+)TILs/CD8^(+)TILs高比值患者,差异均有统计学意义(P<0.05)。多因素Cox回归分析结果显示,PD-L1阳性表达、CD8^(+)TILs高密度是患者预后的独立保护因素(P<0.05)。结论PD-L1、CD4^(+)TILs、CD8^(+)TILs、FoxP3^(+)TILs/CD8^(+)TILs比值与宫颈癌淋巴结转移患者预后均有关,其中PD-L1阳性表达、CD8^(+)TILs高密度是宫颈癌淋巴结转移患者预后的独立保护因素。

HER2低表达乳腺癌组织中p53基因突变与临床病理特征的关系

目的分析人表皮生长因子受体2(human epidermal growth factor receptor 2,HER2)低表达乳腺癌组织中p53基因突变与临床病理特征的关系。方法选择2018年8月—2023年8月厦门市第三医院收治的112例HER2低表达乳腺癌患者为研究对象,所有患者均在厦门市第三医院进行手术切除癌组织,并留取乳腺癌组织。通过银染聚合酶链反应-单链构象多肽性分析法(polymerase chain reaction single strand conformation polymorphism,PCR-SSCP)检测HER2低表达乳腺癌组织p53基因突变情况,分析p53基因突变与HER2低表达乳腺癌临床病理特征的相关性。结果HER2低表达乳腺癌组织中p53基因未突变82例,占比为73.21%;p53基因突变30例,占比为26.79%。p53基因突变与肿瘤直径、淋巴结转移、脉管侵犯、临床分期呈正相关(P<0.05)。将年龄、身体质量指数(body mass index,BMI)、细胞增殖相关抗原(cell proliferation-associated antigens,Ki-67)指数、雌激素受体(estrogen receptor,ER)指数等因素控制后p53基因突变与肿瘤直径、淋巴结转移、脉管侵犯、临床分期相关(P<0.05)。结论HER2低表达乳腺癌组织中p53基因突变率较低,p53基因突变与乳腺癌肿瘤直径、淋巴结转移、脉管侵犯、临床分期相关,为中国抗癌协会乳腺癌诊治指南与规范后期标准制定提供了借鉴内容。

临床病理特征结合SWE参数对乳腺癌腋窝淋巴结转移的预测价值

目的探讨临床病理特征结合剪切波弹性成像(SWE)参数对乳腺癌腋窝淋巴结转移的预测价值。方法将本院收治的72例乳腺癌患者均行SWE检查、同侧腋窝淋巴结清扫或前哨淋巴结活检。根据腋窝淋巴结是否发生转移分为未转移组39例与转移组33例。采用单因素及多因素Logistic分析腋窝淋巴结转移的风险因素。采用ROC曲线评估临床病理特征联合SWE对腋窝淋巴结转移的诊断效能。结果单因素分析结果显示,两组组织学分级、淋巴管血管侵犯、病灶微钙化、Ki-67、淋巴结最大纵径、淋巴结最大横径、淋巴结皮质厚度、弹性模量平均值(E mean)、弹性模量最大值(E max)及弥散度(SD)比较,差异有显著性(P<0.05)。多因素Logistic回归结果显示,淋巴管血管侵犯、组织学分级(Ⅲ级)、E max及SD为乳腺癌患者发生腋窝淋巴结转移的危险因素(P<0.05)。ROC结果显示,组织学分级为Ⅲ级、存在淋巴管血管侵犯、E max≥45.635 kPa、SD≥8.450的联合预测效能高于各指标单独预测效能。结论临床病理特征结合SWE参数对乳腺癌腋窝淋巴结转移具有一定的预测价值。

HER-2低表达的非特殊型浸润性乳腺癌的临床病理特征与腋窝淋巴结转移的危险因素分析

目的探讨人类表皮生长因子受体2(HER-2)低表达的非特殊型浸润性乳腺癌(IBC)的临床病理特征,并分析腋窝淋巴结(ALN)转移的相关危险因素。方法回顾性分析2018年1月至2022年12月在绍兴市妇幼保健院确诊为HER-2阴性的111例非特殊型IBC患者的临床病理资料。其中HER-2免疫组化(IHC)判读为1+或2+且荧光原位杂交未扩增者归为HER-2低表达组(77例),HER-2 IHC判读为0者归为HER-20表达组(34例)。比较两组患者临床病理特征,并采用多因素logistic回归分析影响ALN转移的危险因素。结果HER-2低表达组患者年龄(52.8±10.9)岁、肿瘤大小通常≤2.5 cm、主要位于外上象限、以临床分期Ⅰ/Ⅱ期和组织学Ⅱ级为主。HER-2低表达组患者雌激素受体、孕激素受体、雄激素受体(AR)阳性率及Luminal B型占比均高于HER-20表达组,差异均有统计学意义(均P<0.05)。HER-2低表达组患者ALN转移与肿瘤大小(>2.5 cm)、AR阴性表达状态、Ki-67高表达(≥20%)、Luminal B型、临床分期(Ⅱ/Ⅲ期)均有关(均P<0.05);HER-20表达组患者ALN转移仅与临床分期(Ⅱ/Ⅲ期)有关(P<0.05)。多因素logistic回归分析显示AR阴性表达状态和Luminal B型是影响HER-2低表达组患者ALN转移的危险因素(均P<0.05)。结论HER-2低表达患者具有一定的临床病理特征,激素受体表达状态和分子分型特点均有别于HER-20表达患者,其ALN转移关联的危险因素包括AR阴性表达状态和Luminal B型。

^(18)F-FDG PET/CT代谢参数与宫颈癌临床病理特征、肿瘤标志物及血清转移相关标志物的相关性

目的探讨^(18)F-FDG PET/CT代谢参数与宫颈癌临床病理学特征、肿瘤标志物及血清转移相关标志物的相关性。方法回顾性分析295例宫颈癌患者的临床资料,纳入患者均在治疗前行^(18)F-FDG PET/CT检查,测量并计算宫颈癌原发灶代谢参数,包括最大标准摄取值(maximum standard uptake,SUVmax)、峰值标准摄取值(peak standard uptake,SUVpeak)、肿瘤代谢体积(tumor metabolic volume,MTV)和病灶糖酵解总量(total glycolysis,TLG),分析以上参数与患者临床病理学特点、血清肿瘤标志物和血清转移相关标志物(uPA、CK20、CK19及MMP-9)的相关性。结果高分化型宫颈癌原发灶的MTV值明显高于中分化及低分化宫颈癌(P=0.047)。FIGO分期为Ⅳ期患者的原发灶MTV及TLG值均高于Ⅲ期和Ⅱ期患者(P<0.001)。SCC-Ag≥1.5 ng/mL、CEA≥5 ng/mL和CA125≥35 ng/mL的宫颈癌患者原发灶MTV及TLG值均高于血清SCC-Ag、CEA和CA125水平低者(P<0.05)。血清CK19水平与FIGO分期有关(P=0.029),uPA、CK20及MMP-9均与肿瘤代谢参数和临床病理特征间差异无统计学意义(P>0.05)。结论宫颈癌原发灶代谢参数与其临床病理学特征、FIGO分期及血清肿瘤标志物具有一定的相关性。

血清LDH、ApoA1、TSGF水平与结直肠癌患者临床病理特征的相关性分析及联合诊断价值

目的:探究乳酸脱氢酶(LDH)、载脂蛋白A1(ApoA1)、肿瘤特异性生长因子(TSGF)水平与结直肠癌患者临床病理特征相关性,分析其对结直肠癌的诊断价值。方法:选取2021年1月—2023年1月某院收治的105例结直肠癌患者设为结直肠癌组,同期结直肠腺瘤患者56例设为结直肠腺瘤组,健康体检志愿者35例设为对照组。比较3组血清LDH、ApoA1、TSGF水平。观察结直肠癌组不同临床病理特征者血清LDH、ApoA1、TSGF水平变化,并分析其与临床病理特征相关性;采用受试者工作特征曲线(ROC)分析血清LDH、ApoA1、TSGF水平对结直肠癌的诊断效能。结果:结直肠癌组血清LDH、TSGF水平分别为(302.16±99.52)U/L、(68.52±21.84)U/mL,高于结直肠腺瘤组[(267.49±82.61)U/L、(57.49±16.16)U/mL]和对照组[(201.98±66.36)U/L、(43.28±14.18)U/mL],血清ApoA1水平[(1.33±0.41)g/mL]低于结直肠腺瘤组[(1.58±0.51)g/mL]和对照组[(1.80±0.58)g/mL],差异均有统计学意义(P<0.05)。随着TNM分期增加、淋巴结转移、浆膜浸润发生,血清LDH、TSGF水平呈上升趋势,ApoA1水平呈下降趋势,而随着分化程度增高,血清LDH、TSGF水平呈下降趋势,ApoA1水平呈上升趋势,差异有统计学意义(P<0.05)。血清LDH、TSGF与TNM分期、淋巴结转移、浆膜浸润呈正相关(r LDH=0.526、0.632、0.485;r TSGF=0.574、0.419、0.503,P均<0.05),与分化程度呈负相关(r LDH=-0.412;r TSGF=-0.567,P均<0.05),而ApoA1与TNM分期、淋巴结转移、浆膜浸润呈负相关(r=-0.528、-0.557、-0.601,P<0.05),与分化程度呈正相关(r=0.496,P<0.05)。血清LDH、ApoA1、TSGF联合检测诊断结直肠癌的AUC为0.901,大于单项指标诊断。结论:结直肠癌患者血清LDH、TSGF呈高表达,ApoA1呈低表达,其中血清LDH、TSGF与TNM分期、淋巴结转移、浆膜浸润呈正相关,与分化程度呈负相关,而ApoA1与之相反,联合检测其水平对结直肠癌具有一定诊断价值。

基于巢式病例对照研究影响乳腺癌术后转移的膳食因素

目的探讨膳食因素与乳腺癌术后转移的关系,为该人群的饮食干预提供依据。方法基于2013年西南医科大学附属医院乳腺外科建立的乳腺癌队列,以2013年1月至2018年12月随访发现的乳腺癌转移者140例为病例组,按照年龄±3岁,对照组与病例组行乳腺癌根治手术时间差应该控制在一个月范围内,手术方式和术后辅助治疗方案等一致,排除术前已经出现复发转移或合并其他器官肿瘤疾病的患者等1∶1匹配,以同期未发生乳腺癌转移的患者140例为对照组,比较两组的病理资料、食物频率等,使用SPSS 20.0进行单因素分析和多因素lo-gistic回归分析筛选出导致乳腺癌术后转移的独立危险因素。结果单因素分析结果显示肉类、蔬菜类、水果类的摄入量在转移组和对照组之间的差异具有统计学意义(P<0.001)。多因素条件Logistic回归模型结果显示每日食用少于推荐摄入量的蔬菜[OR值(95%CI)为5.068(1.873~13.716),P<0.001]、每日食用少于推荐摄入量的水果[OR值(95%CI)为8.119(2.721~24.228),P<0.001]、每日食用超过推荐摄入量的肉类[OR值(95%CI)为5.009(1.847~13.585),P<0.05]均是乳腺癌患者术后发生转移的独立危险因素。结论每日食用少于推荐摄入量的蔬菜(<200 g)和水果(<300 g),每日食用超过推荐摄入量的肉类(>75 g)均是乳腺癌术后转移的独立危险因素,影响患者的预后。

潜在转化生长因子β结合蛋白4影响肿瘤细胞伪足形成抑制结直肠癌转移的分子机制研究

目的 探究潜在转化生长因子β结合蛋白4(latent transforming growth factor beta binding protein 4,LTBP4)通过影响肿瘤细胞伪足形成从而遏制结直肠癌细胞转移的分子机制。方法 在结直肠癌细胞株DiFi中使用小干扰si-LTBP4敲减LTBP4,在结直肠癌细胞株HCT15中使用LTBP4过表达质粒过表达LTBP4。使用人源慢病毒在DiFi细胞株中稳定敲减/不敲减LTBP4构建稳转细胞株shLTBP4和shNC。Western blot法检测LTBP4、原肌球蛋白4(tropomyosin 4,TPM4)、金属基质蛋白酶14(matrix metalloproteinase-14,MMP14)及酪氨酸激酶底物5(tyrosine kinase substrate 5,TKS5)等蛋白。实时荧光定量PCR(quantitative real-time PCR,qPCR)检测LTBP4及TPM4的表达。Transwell迁移实验检测敲低/过表达LTBP4后结直肠癌细胞的体外转移能力。使用裸鼠尾静脉注射shLTBP4或shNC稳转细胞株构建裸鼠肺转移模型及阴性对照,检测结直肠癌细胞敲减LTBP4后的体内转移能力。转录组测序检测差异基因表达情况。鬼笔环肽染色观察敲低LTBP4后细胞骨架改变及侵袭性伪足形成情况。结果 qPCR实验检测发现,LTBP4在DiFi、HCT8和KM12C细胞株中均高表达(均P<0.05),在HCT15和KM12SM细胞株中均低表达(均P<0.01)。Westen blot检测发现,LTBP4在DiFi、HCT8和KM12C细胞株中均高表达(均P<0.01),在HCT15、KM12SM及RKO细胞株中均低表达(均P<0.05)。在高表达LTBP4的DiFi细胞株中转染小干扰si-LTBP4,敲低LTBP4,转染后72 h后进行transwell迁移实验发现,肿瘤细胞迁移能力增强(P<0.01);而在低表达LTBP4的HCT15细胞株中过表达LTBP4,72 h后肿瘤细胞迁移能力减弱(P<0.01)。裸鼠肺转移模型在通过尾静脉注射稳转细胞株shLTBP4以及shNC 5周后进行小动物活体荧光成像发现,敲减LTBP4后,小鼠肺部荧光信号增强(P<0.01)。高通量转录组测序发现,在DiFi细胞株中敲减LTBP4使细胞骨架蛋白TPM4的表达量增加(P<0.01),维持细胞运动功能(如肌动蛋白丝束收缩、应力纤维改变和肌动蛋束的调节)相关通路显著富集(均P<0.05)以及细胞形态改变相关通路(如轴突伸展调节、突触前膜、核孔和活性离子跨膜传输等)显著富集(均P<0.05)。Western blot、qPCR及免疫荧光实验验证DiFi细胞株中敲减LTBP4促进细胞运动相关蛋白TPM4的表达(均P<0.01)。结论 LTBP4可以通过调控TPM4的方式抑制侵袭性伪足的形成从而遏制结直肠肿瘤细胞的转移。

组织中P53、人表皮生长因子受体2表达与乳腺癌患者临床病理特征的关系

目的:探讨组织中P53、人表皮生长因子受体2(HER2)表达与乳腺癌患者临床病理特征的关系.方法:选取2019年2月至2023年2月于本院采取手术治疗的60例乳腺癌患者作为研究对象.检测其组织中P53、HER2表达,分析其阳性表达与乳腺癌患者不同临床病理特征的相关性.结果:60例乳腺癌患者肿瘤组织中,P53、HER2阳性率分别为53.33%(32/60)和45%(27/60).Ⅲ期、组织低分化、发生淋巴结转移乳腺癌患者的P53、HER2阳性率,显著高于Ⅰ/Ⅱ期、组织中高分化、未发生淋巴结转移者,差异均有统计学意义(P<0.05).乳腺癌患者肿瘤组织中P53、HER2阳性表达,与肿瘤分期、淋巴结转移情况呈正相关关系(r>0,P<0.05),与组织分化程度呈负相关关系(r<0,P<0.05).结论:乳腺癌患者肿瘤组织中P53、HER2多呈阳性表达.肿瘤分期、组织分化程度、淋巴结转移情况,可能与P53、HER2表达有关.

Over-expression of VEGF and MMP-9 in Residual Tumor Cells of Hepatocellular Carcinoma after Embolization with Lipidol

The expression and implication of vascular endothelial growth factor （VEGF） and matrix metalloproteinase-9 （MMP-9） in residual hepatic tumor cells after lipiodol embolization were investi- gated. Two weeks after transplantation of VX2 tumor cells into the livers of rabbits, a xenograft model of the human hepatic neoplasm was successfully established. Forty rabbits were randomly divided into control group （n=20） and lipiodol group （n=20）. For the control group, 1 mL normal saline was injected through the gastroduodenal artery, whereas 0.3 mL/kg lipiodol was applied for the lipiodol group. One week after embolization, the expression level of VEGF in the plasma was measured by using en- zyme-linked immunosorbent assay （ELISA）. A three-step immunohistochemieal technique （ABC） was employed to detect the protein levels of VEGF and MMP-9 and the quantitative PCR for their mRNA levels was performed in the residual tumor cells. The VEGF in the plasma was significantly higher in the lipiodol group （1.42~0.29 ng/mL） than in the control group （1.12~0.21 ng/mL） （P〈0.01）. Moreover, the positive rate of VEGF protein in the residual tumor cells was significantly higher in the lipiodol group （62.13%~7.69%） than in the control group （53.16%~9.17%） （P〈0.05）. Similarly, the MMP-9 ex- pression in the residual ~mor cells was higher in the lipiodol group. The mRNA levels of VEGF （2.9313~2.4231） and MMP-9 （3.5721~1.6107） in the lipiodol group were significantly higher than those in the control group （1.5728~0.9453 and 1.7573~1.0641, respectively, P〈0.05）. Therefore, it was rea- sonable to speculate that the increased expression of VEGF and MMP-9 in residual hepatic tumor cells and tumor angiogenesis post-embolization would be responsible for the increased metastatic potentiality and invasiveness of these cells.

Effect of non-anticoagulant N-desulfated heparin on expression of vascular endothelial growth factor, angiogenesis and metastasis of orthotopic implantation of human gastric carcinoma

AIM： To investigate the effect of N-desulfated heparin on tumor metastasis and angiogenesis, and expression of vascular endothelial growth factor （VEGF） of orthotopic implantation of human gastric carcinoma in male severe combined immune deficiency （SCID） mice. METHODS： Human gastric cancer SGC-7901 cells were orthotopically implanted into the stomach of SC/D mice. The mice were randomly divided into normal saline group and N-desulfated heparin group. One week after operation, the mice in N-desulfated heparin group reo ceived i.v. injections of N-desulfated heparin （Shanghai Institute of Cell Biology, Chinese Academy of Sciences, 10 mg/kg.d） twice weekly for 3 wk. The mice in normal saline group received i.v. injections of normal saline （100 μL） twice weekly for 3 wk. The mice were sacrificed six weeks after implantation. Tumor metastasis was evaluo ated histologically for metastasis under microscope. Intratumoral microvessel density （MVD） and VEGF expression were evaluated immuohistochemically. VEGF mRNA expression in gastric tissue of SC/D mice was detected by real time PCR. RESULTS： The tumor metastasis rate was 80% in normal saline group and 20% in N-desulfated heparin group （P 〈 0.05）. MVD was 8.0 ± 3.1 in normal saline group and 4.3 ± 1.8 in N-desulfated heparin group （P 〈 0.05）. VEGF positive immunostaining was found in cytoplasm of cancer cells. The rate of VEGF positive expression was higher in normal saline group than in N-desulfated hepa- rin treated group （90% vs 20%, P 〈 0.05）. VEGF mRNA expression was significantly inhibited by N-desulfated heparin and was higher in normal saline group than in N-desulfated heparin group （Ct value 19.51 ± 1.01 vs 22.55± 1.36, P 〈 0.05）. N-desulfated heparin significantly inhibited the expression of VEGF mRNA in cancer cells. No bleeding occurred in N-desulfated heparin group. CONCLUSION： N-desulfated heparin can inhibit metastasis of gastric cancer by suppressing tumor VEGF expression and tumor angiogenesis, but has no obvious anticoagulant activity.