Aneuploidy of chromosome 8 in circulating tumor cells correlates with prognosis in patients with advanced gastric cancer

Objective： Previous work indicated that aneuploidy of chromosome 8 in circulating tumor cells（CTCs）correlated with therapeutic efficacy for advanced gastric cancer（AGC） patients. In this follow-up study performed on the same population of AGC patients, we investigated whether and how aneuploidy of chromosome 8 in CTCs correlates with patients＇ clinical prognosis.Methods： The prospective study was performed on 31 patients with newly diagnosed AGC. Previously established integrated subtraction enrichment（SE） and immunostaining-fluorescence in situ hybridization（i FISH）platform was applied to identify, enumerate and characterize CTCs. Quantification of CTCs and analysis of their aneuploidy of chromosome 8 were performed on patients before and after therapy.Results： CTCs were measured in 93.5% of AGC patients, and two CTC subtypes with diverse threshold values were identified, multiploid CTCs with the threshold of ≥2 per 7.5 m L and multiploid plus triploid CTCs with the threshold of ≥4, which were found to significantly correlate with poor progression-free survival（PFS） and overall survival（OS）. In particular, patients with ≥10% increased multiploid CTCs after an initial 6 weeks of therapy had poor PFS and OS, whereas improved PFS and OS were observed on those who had ≥10% decreased multiploid CTCs. After adjusting for clinically significant factors, ≥10% increased post-therapy multiploid CTCs was the only independent predictor of PFS and OS.Conclusions： Aneuploidy of CTCs correlates with prognosis of AGC patients. Quantitative comparison monitoring multiploid CTCs before and after therapy may help predict improved or inferior prognosis and chemoresistance.

Evaluation of epithelial-mesenchymal transitioned circulating tumor cells in patients with resectable gastric cancer: Relevance to therapy response

AIM: To evaluate the epithelial-to-mesenchymal transition(EMT) of circulating tumor cells(CTCs) in gastric cancer patients.METHODS: We detected tumor cells for expression of four epithelial(E^+) transcripts(keratins 8, 18, and 19 and epithelial cell adhesion molecule) and two mesenchymal(M^+) transcripts(Vimentin and Twist) by a quantifiable, dual-colorimetric RNA-in situ hybridization assay. Between July 2014 and October 2014, 44 patients with gastric cancer were recruited for CTC evaluation. Blood samples were obtained from selected patients during the treatment course [before surgery, after surgery and at the 6^(th) cycle of XELOX based chemotherapy(about 6 mo postoperatively)].RESULTS: We found the EMT phenomenon in which there were a few biphenotypic E^+/M^+ cells in primary human gastric cancer specimens. Of the 44 patients, the presence of CTCs was reported in 35(79.5%) patients at baseline. Five types of cells including from exclusively E^+ CTCs to intermediate CTCs and exclusively M^+ CTCs were identified(4 patients with M^+ CTCs and 10 patients with M^+ or M^+ > E^+ CTCs). Further, a chemotherapy patient having progressive disease showed a proportional increase of mesenchymal CTCs in the post-treatment blood specimens. We used NCI-N87 cells to analyze the linearity and sensitivity of Can Patrol^(TM) system and the correlation coefficient(R^2) was 0.999.CONCLUSION: The findings suggest that the EMT phenomenon was both in a few cells of primary tumors and abundantly in CTCs from the blood of gastric cancer patients, which might be used to monitor therapy response.

Prognostic and predictive blood biomarkers in gastric cancer and the potential application of circulating tumor cells

Gastric cancer(GC), with its high incidence and mortality rates, is a highly fatal cancer that is common in East Asia particularly in China. Its recurrence and metastasis are the main causes of its poor prognosis. Circulating tumor cells(CTCs) or other blood biomarkers that are released into the circulating blood stream by tumors are thought to play a crucial role in the recurrence and metastasis of gastric cancer. Therefore, the detection of CTCs and other blood biomarkers has an important clinical significance; in fact, they can help predict the prognosis, assess the staging, monitor the therapeutic effects and determine the drug susceptibility. Recent research has identified many blood biomarkers in GC, such as various serum proteins, autoantibodies against tumor associated antigens, and cell-free DNAs. The analysis of CTCs and circulating cell-free tumor DNA(ctDNA) in the peripheral blood of patients with gastric cancer is called as liquid biopsy. These blood biomarkers provide the disease status for individuals and have clinical meaning. In this review, we focus on the recent scientific advances regarding CTCs and other blood biomarkers, and discuss their origins and clinical meaning.

Epithelial-mesenchymal transition contributes to malignant phenotypes of circulating tumor cells derived from gastric cancer

Circulating tumor cells(CTCs)are crucial to tumor metastasis,and they usually undergo epithelial-mesenchymal transition(EMT)in order to disseminate from the primary tumor.However,very little is currently known about the relationship between EMT and malignant phenotypes of CTCs in the context of gastric cancer.Therefore,this study aimed to investigate the contribution of EMT to malignant phenotypes of CTCs derived from gastric cancer cells.We xenografted MKN28 gastric cancer cells pretreated with transforming growth factor-beta 1(TGFβ-1)into nude mice by intravenous injection.Next,we isolated CTCs from the blood of nude mice by gradient centrifugation and found that CTCs derived from MKN28 cells pretreated with TGFβ-1 had a significantly increased viability and invasion ability compared to MKN28 cells without TGFβ-1 treatment.Immunocytochemical staining showed lower expression of E-cadherin and higher expression of N-cadherin,vimentin,and β-catenin in CTCs derived from MKN28 cells pretreated with TGFβ-1.Furthermore,the expression of Wnt3a,β-catenin,cyclin D1,and c-Myc was significantly higher in CTCs derived from MKN28 cells pretreated with TGFβ-1.Taken together,these findings suggest that TGFβ promotes EMT and malignant phenotypes of gastric cancer cells.Furthermore,the malignant phenotypes of gastric cancer cells induced by TGFβ are maintained in CTCs derived from these cells.Targeting EMT in CTCs is a new approach to the treatment of gastric cancer relapse and metastasis.

Level of circulating PD-L1 expression in patients with advanced gastric cancer and its clinical implications

Objective：The programmed cell death-1 receptor/programmed cell death-1 ligand （PD-1/PD-L1） pathway plays a crucial role in tumor evasion from host immunity.This study was designed to evaluate the association between circulating PD-L1 expression and prognosis in patients with advanced gastric cancer.Methods：Totally 80 advanced gastric cancer patients and 40 health controls from Beijing Cancer Hospital were enrolled in the present study.Circulating PD-L1 expression was tested by enzymelinked immunosorbent assay （ELISA）.The associations between the expression level of PD-L1 and clinicopathological features and prognosis were analyzed statistically.Results：Expression of PD-L1 in advanced gastric cancer patients was significandy up-regulated compared with health people （P=0.006）.The expression of PD-L1 was significantly correlated with differentiation and lymph node metastasis （P=0.026 and P=0.041,respectively）.Although we didn＇t find significant difference in all advanced gastric cancer patients with different PD-L1 expression,the adenocarcinoma patients with higher up-regulated PD-L1 expression had much better prognosis than low expression patients （65.6％ vs.44.7％,P=0.028）.Conclusions：PD-L1 was elevated in advance gastric cancer patients and may play an important role in tumor immune evasion and patients prognosis.

Cryopreservation for delayed circulating tumor cell isolation is a valid strategy for prognostic association of circulating tumor cells in gastroesophageal cancer

AIM To demonstrate the feasibility of cryopreservation of peripheral blood mononuclear cells(PBMCs) for prognostic circulating tumor cell(CTC) detection in gastroesophageal cancer.METHODS Using 7.5 m L blood samples collected in EDTA tubes from patients with gastroesopheagal adenocarcinoma, CTCs were isolated by epithelial cell adhesion molecule based immunomagnetic capture using the Iso Flux platform. Paired specimens taken during the same blood draw(n = 15) were used to compare number of CTCs isolated from fresh and cryopreserved PBMCs. Blood samples were processed within 24 h to recover the PBMC fraction, with PBMCs used for fresh analysis immediately processed for CTC isolation. Cryopreservation of PBMCs lasted from 2 wk to 25.2 mo(median 14.6 mo). CTCs isolated from pre-treatment cryopreserved PBMCs(n = 43) were examined for associations with clinicopathological variables and survival outcomes.RESULTS While there was a significant trend to a decrease in CTC numbers associated with cryopreserved specimens(mean number of CTCs 34.4 vs 51.5, P = 0.04), this was predominately in samples with a total CTC count of > 50, with low CTC count samples less affected(P = 0.06). There was no significant association between the duration of cryopreservation and number of CTCs. In cryopreserved PBMCs from patient samples prior to treatment, a high CTC count(> 17) was associated with poorer overall survival(OS)(n = 43, HR = 4.4, 95%CI: 1.7-11.7, P = 0.0013). In multivariate analysis, after controlling for sex, age, stage, ECOG performance status, and primary tumor location, a high CTC count remained significantly associated with a poorer OS(HR = 3.7, 95%CI: 1.2-12.4, P = 0.03). CONCLUSION PBMC cryopreservation for delayed CTC isolation is a valid strategy to assist with sample collection, transporting and processing.

Liquid biopsy of gastric cancer patients:Circulating tumor cells and cell-free nucleic acids

To improve the clinical outcomes of cancer patients, early detection and accurate monitoring of diseases are necessary. Numerous genetic and epigenetic alterations contribute to oncogenesis and cancer progression, and analyses of these changes have been increasingly utilized for diagnostic, prognostic and therapeutic purposes in malignant diseases including gastric cancer (GC). Surgical and/or biopsy specimens are generally used to understand the tumor-associated alterations; however, those approaches cannot always be performed because of their invasive characteristics and may fail to reflect current tumor dynamics and drug sensitivities, which may change during the therapeutic process. Therefore, the importance of developing a non-invasive biomarker with the ability to monitor real-time tumor dynamics should be emphasized. This concept, so called “liquid biopsy”, would provide an ideal therapeutic strategy for an individual cancer patient and would facilitate the development of “tailor-made” cancer management programs. In the blood of cancer patients, the presence and potent utilities of circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) such as DNA, mRNA and microRNA have been recognized, and their clinical relevance is attracting considerable attention. In this review, we discuss recent developments in this research field as well as the relevance and future perspectives of CTCs and cfNAs in cancer patients, especially focusing on GC.

Liquid biopsy for gastric cancer:Techniques,applications,and future directions

After the study of circulating tumor cells in blood through liquid biopsy(LB),this technique has evolved to encompass the analysis of multiple materials originating from the tumor,such as nucleic acids,extracellular vesicles,tumor-educated platelets,and other metabolites.Additionally,research has extended to include the examination of samples other than blood or plasma,such as saliva,gastric juice,urine,or stool.LB techniques are diverse,intricate,and variable.They must be highly sensitive,and pre-analytical,patient,and tumor-related factors significantly influence the detection threshold,diagnostic method selection,and potential results.Consequently,the implementation of LB in clinical practice still faces several challenges.The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases,monitoring treatment response,early identification of relapses,or assessing patient risk.On the other hand,gastric cancer(GC)is a disease often diagnosed at advanced stages.Despite recent advances in molecular understanding,the currently available treatment options have not substantially improved the prognosis for many of these patients.The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients.In this comprehensive review,from a pathologist’s perspective,we provide an overview of the main options available in LB,delve into the fundamental principles of the most studied techniques,explore the potential utility of LB application in the context of GC,and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.

High circulating tumor cell concentrations in a specific subtype of gastric cancer with diffuse bone metastasis at diagnosis

AIM: To clarify the biological feature contributing to gastric cancer with diffuse bone metastases at diagnosis.METHODS: The participants visited the Department of Clinical Oncology, Akita University Hospital, from January 2014 to August 2015. The selection criterion for gastric cancer with diffuse bone metastases at diagnosis includes over 29 hot spots of bone scintigraphy. Circulating tumor cell were collected from 20 m L of peripheral venous blood drawn using a Cell Search kit and a Cell Tracks Auto Prep system by SRL, a clinical laboratory. The endpoints of this study were correlations between circulating tumor cells(CTC) count and therapeutic outcomes. RESULTS: Among 39 patients with gastric cancer, 5 patients met the criterion. The incidence of this subtype was 12.8%. CTC counts ranged from 235 to 6440 cells/7.5 m L of peripheral blood(median of 1724). These values were much higher than common gastric cancers(2 cells). In chemo-sensitive cases, CTC counts decreased within 14 d(median) from 275, 235 and 1724 to 2, 7 and 66, respectively. On the other hand, CTC counts increased after treatment failure or insensitive case from 2, 7 and 6440 to 787, 513 and 7885, respectively. The correlation between CTC count and survival time showed a trend, but did not reach significance(Y = 234.6- 0.03 X, P = 0.085).CONCLUSION: High CTC count is a biological hallmark of this subtype, and can be used as a direct and definitive indicator of therapeutic outcome.

New blood markers detection technology:A leap in thediagnosis of gastric cancer

Gastric cancer(GC) is still one of the malignant tumors with high morbidity and mortality in the world, with a 5-year survival rate of less than 30%. GC is often either asymptomatic or causes only nonspecific symptoms in its early stages, whereas when the symptoms manifest, the cancer has usually reached an advanced stage, which is one of the main causes of its relatively poor prognosis. Hence, the main focus of GC research has been on discovering new tools and technology to predict, screen and diagnose g C at an early stage which would prompt early treatment. With the tremendous advances in the OMICS technology, serum proteomics has been in the limelight of cancer research over the last few decades and has steered the development of several methods helping to understand the mechanisms underlying gastric carcinogenesis, resulting in the identification of a large number of molecular targets such as circulating tumor cells(CTCs), cell free DNA(cf DNA) and cell tumor DNA(ct DNA) and their sub-molecular components such as mi RNA, that show great promise as GC biomarkers. In this review, we are underlying the recent breakthroughs about new blood markers technology for GC while scrutinizing the potential clinical use of CTCs, cf DNA, ct DNA and the role of the methylation of their submolecular components in the pathogenesis, diagnosis and management of GC.

外周血循环肿瘤细胞与胃癌患者临床病理特征及新辅助化疗疗效的关系

目的探讨外周血循环肿瘤细胞(CTC)与胃癌患者临床病理特征及新辅助化疗疗效的关系。方法选择2015年3月至2016年2月新乡医学院第三附属医院收治的112例胃癌患者为研究对象。所有患者均于治疗前1 d抽取空腹外周静脉血4 mL,采用阴性富集联合免疫荧光法检测外周血CTC,根据CTC检测结果将患者分为CTC阳性组和CTC阴性组。2组患者均给予新辅助化疗,奥沙利铂130 mg·m^(-2),静脉滴注,第1天;卡培他滨1000 mg·m^(-2),口服,每日2次,第1~14天;21 d为1个疗程,共治疗3个疗程。比较2组患者临床病例特征。采用Kappa检验分析实体瘤疗效评价标准(RECIST)和CTC数目评价标准的一致性,应用Kaplan-Meier生存分析计算患者3、5 a累积生存率,log-rank检验比较CTC阳性组和CTC阴性组患者治疗后3、5 a累积生存率。结果112例胃癌患者中,64例(57.14%)外周血CTC阳性,48例(42.86%)外周血CTC阴性。经新辅助化疗后,完全缓解、部分缓解、疾病稳定、疾病进展者分别为0例、76例、21例、15例,治疗总有效率为67.86%(76/112)。CTC阳性组患者肿瘤浸润深度、TNM分期与CTC阴性组比较差异有统计学意义(P<0.05);CTC阳性组与CTC阴性组患者的性别、年龄、病理分型、肿瘤大小、肿瘤位置、肿瘤分化程度、脉管癌栓比较差异均无统计学意义(P>0.05)。CTC阳性组患者治疗总有效率为59.38%(38/64),CTC阴性组患者治疗总有效率为79.17%(38/48);CTC阳性组患者治疗总有效率显著低于CTC阴性组(χ^(2)=4.926,P<0.05)。RECIST评价标准与CTC数目评价标准具有中度一致性(Kappa=0.546)。CTC阳性组患者3、5 a累积生存率分别为75.6%、26.7%,CTC阴性组患者3、5 a累积生存率分别为85.2%、46.6%。CTC阳性组患者3 a累积生存率与CTC阴性组比较差异无统计学意义(P>0.05);CTC阳性组患者5 a累积生存率显著低于CTC阴性组(P<0.05)。结论检测CTC有助于评估胃癌患者肿瘤浸润程度、临床分期,且能够评估新辅助化疗效果,并对患者的远期生存情况有一定预测价值。

叶酸受体阳性循环肿瘤细胞检测在胃癌患者中的临床意义及相关性分析

目的 研究叶酸受体阳性循环肿瘤细胞(folate receptor positive circulating tumor cells, FR+CTC)检测在胃癌患者中的临床意义。方法 回顾性分析术前检测过FR+CTC表达量的胃癌手术患者的临床资料。绘制FR+CTC、白蛋白、总蛋白、血红蛋白、CA125、CA199及CEA预测胃癌患者合并腹膜转移、淋巴结转移、脉管侵犯、神经侵犯、肿瘤突破浆膜层及进展期胃癌的ROC曲线。研究FR+CTC值与胃肠道肿瘤标志物和临床常用营养指标相关的相关性。探讨FR+CTC值及临床相关指标在不同类型胃癌中表达量的统计学差异情况。结果 FR+CTC诊断胃癌患者合并腹膜转移、淋巴结转移、脉管侵犯、神经侵犯、肿瘤突破浆膜层及Ⅲ~Ⅳ期胃癌的AUC值分别为0.933、0.653、0.614、0.628、0.714、0.703,明显优于传统肿瘤标志物(CEA、CA199、CA125)。通过Spearman相关性分析显示,FR+CTC值与白蛋白含量呈负相关(R=-0.26,P=0.0043)。FR+CTC表达量在腹膜转移、淋巴结转移、脉管侵犯、神经侵犯、肿瘤突破浆膜层及Ⅲ~Ⅳ期胃癌患者中明显增加,差异均有统计学意义(P<0.05)。结论 FR+CTC值较传统肿瘤标志物能更准确地预测胃癌患者合并腹膜转移、淋巴结转移、脉管侵犯、神经侵犯、肿瘤突破浆膜层及肿瘤处于Ⅲ~Ⅳ期的概率,并且FR+CTC在这些类型胃癌患者中表达量明显增加,可常规作为新型的临床肿瘤标志物。

胃癌循环肿瘤细胞与临床病理特征及预后的相关性研究

目的研究胃癌循环肿瘤细胞(CTCs)及其亚型与临床病理特征及预后的相关性。方法采取前瞻性研究方法,随机选择2015年5月至2019年1月期间在广西医科大学附属肿瘤医院胃肠外科就诊,经病理诊断为胃腺癌并符合入组条件的初始治疗患者作为研究对象,利用Canpatrol TM技术平台富集分离入组病例术前外周血CTCs,采取多重原位mRNA杂交技术对CTCs进行鉴定、分型并计数;分析CTCs及其亚型与患者年龄、性别、分化程度、神经侵犯、脉管侵犯、Lauren分型、肿瘤部位、浸润深度(T分期)、淋巴结转移(N分期)、AJCC病理分期之间的相关性;对所有入组病例进行随访,分析CTCs与预后相关性。结果共入组病例58例,其中男性37例,女性21例,平均年龄54.4岁;基于Canpatrol TM技术平台,将CTCs分为上皮型(eCTCs)、混合型(mixCTCs)及间质型(mCTCs)3个亚型;CTCs总检出率为90.7%,其中eCTCs检出率68.5%,mixCTCs检出率74.1%;mCTCs检出率61.1%;CTCs及其亚型检出数量与年龄及Lauren分型相关,年龄<60岁的胃癌病例术前外周血CTCs总数及mixCTCs显著低于年龄≥60岁的胃癌病例,P=0.016;Lauren肠型胃癌中CTCs总数及eCTCs、mCTCs数量显著高于弥漫型胃癌(P<0.05);CTCs及其亚型检出数量与病理分期无显著相关性(P>0.05),但当按Lauren分型进行分层后,肠型胃癌组eCTCs数量与病理分期显著正相关(P<0.05);CTCs及其亚型检出数量与性别、神经脉管侵犯、肿瘤部位、浸润深度(T分期)、淋巴结转移(N分期)等指标均无明显相关(P>0.05);本组病例平均随访时间50个月尚未到达中位生存时间,进一步COX回归分析提示肿瘤TNM分期、Lauren分型、神经侵犯是胃癌独立预后因子,CTCs检出数量与生存预后无相关性。结论胃癌外周血CTCs检测到不同上皮-间质标记亚群,提示胃癌外周血CTCs存在上皮-间质转化(EMT)现象;胃癌外周血CTCs及其亚型数量与Lauren分型显著相关,肠型胃癌CTCs检出数量与病理分期关系密切,提示胃癌CTCs的检测在肠型胃癌的预后监测方面可能更有应用价值。

Circulating tumor cells in gastric cancer

Circulating tumor cells(CTCs)have received a lot of attention as a novel biomarker for cancer research in past decades.CTCs infiltrate the bloodstream derived from the primary tumor,and are significantly involved in cancer metastasis and recurrence.Although clinical applications have been challenging owing to the difficulties of CTC identification,recent development of technology for specific enrichment and detection of CTCs contributes to diagnosis and treatment.Furthermore,CTC analyses will shed new light on the biological mechanisms of cancer progression and metastasis.A number of clinical studies have already been carried out on the basis of CTC technology.Nevertheless,the clinical utility of CTCs is still unknown in gastric cancer.In this review,we elaborate on the latest advances of CTC research in gastric cancer.

CTC联合NLR预测可切除老年原发性胃癌患者术后辅助化疗疗效和预后的临床研究

目的探讨循环肿瘤细胞(CTC)联合中性粒细胞计数和淋巴细胞计数比(NLR)在可切除老年原发性胃癌患者术后辅助化疗疗效和预后中的预测效果。方法选择江苏省肿瘤医院2017年12月至2020年12月可切除老年原发性胃癌患者93例为观察组;选择同期健康体检志愿者51例血清标本为对照组。观察组患者均连续完成6个月化疗,根据化疗疗效分为化疗不敏感组及化疗敏感组,比较两组CTC和NLR水平并分析其在辅助化疗疗效中的诊断效能;Kaplan-meier法绘制不同CTC和NLR表达患者的总生存时间(OS)和无进展生存时间(PFS)曲线,生存差异行Log-rank检验。结果观察组NLR高于对照组[2.90(2.15,4.20)vs.1.89(1.50,2.42),Z=-6.382,P<0.05];93例患者辅助化疗后不敏感组32例,化疗敏感组61例;化疗不敏感组患者NLR及CTC水平高于化疗敏感组(P<0.05)。受试者工作特征曲线(ROC)分析,NLR诊断化疗疗效的曲线下面积(AUC)为0.714(95%CI:0.612~0.815),当截断值为2.24时,灵敏度高达100%,特异度为41.0%;当NLR联合CTC时,AUC=0.806(95%CI:0.709~0.903),灵敏度78.14%,特异度为75.43%。仅NLR与患者年龄有关(P<0.05)。CTC高表达患者中位OS和中位PFS为22.0个月和15.0个月,均低于CTC低表达患者的27.0个月和20.0个月,差异均有统计学意义(P<0.05)。NLR高表达患者中位OS和中位PFS为22.0个月和14.0个月,均低于NLR低表达患者的30.0个月和19.0个月,差异均有统计学意义(P<0.05)。结论NLR联合CTC可预测患者辅助化疗疗效及预后,作为判断患者治疗效果及预后的潜在指标。

华蟾素联合阿帕替尼治疗晚期胃癌二线化疗失败患者疗效观察及对免疫失衡、血清肿瘤标志物及相关血清学指标的影响

目的:观察华蟾素联合阿帕替尼治疗晚期胃癌二线化疗失败患者的近期疗效及对外周血辅助性T细胞(Th) 17/调节性T细胞(Treg)免疫失衡、血清肿瘤标志物及相关血清学指标的影响。方法:选择82例二线化疗失败的晚期胃癌患者作为研究对象,以随机数字表法分为观察组和对照组各41例。对照组予阿帕替尼治疗,观察组在对照组基础上联合华蟾素治疗,4周为1个疗程,连续治疗3个疗程。比较2组近期疗效及毒副反应情况,以及治疗前后血清肿瘤标志物[糖类抗原(CA) 72-4、CA19-9、CA242、癌胚抗原(CEA)]水平、相关血清学指标[血管内皮生长因子A (VEGF-A)、表皮生长因子受体(EGFR)、基质金属蛋白酶-9 (MMP-9)]及外周血Th17、Treg水平。结果:观察组客观缓解率为36.59%,对照组为24.39%,2组比较,差异无统计学意义(P>0.05);观察组疾病控制率为73.17%,对照组为51.22%,2组比较,差异有统计学意义(P<0.05)。治疗后,2组血清CA72-4、CA19-9、CA242、CEA水平均较治疗前降低(P<0.05),且观察组上述4项水平均低于对照组(P<0.05)。治疗后,2组外周血Th17、Treg表达水平和Th17/Treg比值均较治疗前降低(P<0.05),且观察组上述3项水平均低于对照组(P<0.05)。治疗后,2组血清VEGF-A、EGFR、MMP-9水平均较治疗前降低(P<0.05),且观察组上述3项水平均低于对照组(P<0.05)。观察组胃肠道反应、高血压、白细胞减少、血小板减少、蛋白尿、乏力、手足综合征的发生率均低于对照组,且2组白细胞减少、血小板减少、乏力发生率比较,差异有统计学意义(P<0.05)。结论:华蟾素联合阿帕替尼治疗二线化疗失败的晚期胃癌能有效下调患者血清肿瘤标志物和VEGF-A、EGFR、MMP-9水平,纠正外周血Th17/Treg免疫失衡,提高近期疗效,并能在一定程度上减少阿帕替尼引起的毒副反应。

胃癌患者的CTC数目与临床病理特征和肿瘤标志物的关系

目的:分析胃癌患者的循环肿瘤细胞(Circulating Tumor Cell,CTC)数目与临床病理特征和肿瘤标志物的关系。方法:选取2019年1月至2022年12月本院收治的78例胃癌患者及78例健康志愿者进行研究,分为观察组和对照组。入院日清晨空腹,两组各抽取外周血7mL,使用细胞搜索系统(Cell search system,CSS)对血液中CTC数目进行计数,分析CTC数目与患者的年龄、性别、临床分期、肿瘤标志物癌胚抗原(Carcinoembryonic antigen,CEA)、糖类抗原199(Carbohydrate antigen199,CA199)、血清糖类抗原72-4(Carbohydrate antigen72-4,CA72-4)的关系。结果:观察组患者CTC阳性数和阳性率均高于对照组(P<0.05)。不同性别及年龄胃癌患者的CTC数目相比,差异无统计学意义(P>0.05)。T1-2期胃癌患者的CTC阳性率与T3-4患者相比,无明显差异(P>0.05);N0-1胃癌患者的CTC阳性率明显低于N2-3的患者,M0患者CTC阳性率明显低于M1患者,Ⅲ-Ⅳ期胃癌患者CTC阳性率明显高于Ⅰ-Ⅱ期,有显著性差异(P<0.05)。CA724含量>6.0组的CTC阳性率明显高于CA724含量≤6.0的患者(P<0.05);不同含量CA199、CEA患者的CTC数目相比差异无统计学意义(P>0.05)。结论:胃癌患者的CTC阳性率较高,CTC数目与胃癌患者的临床病理特征、肿瘤标志物有一定相关性,有助于早期胃癌诊断,值得在临床中推广应用。

安罗替尼联合程序性死亡受体-1抑制剂治疗晚期胃癌临床评价

目的探讨安罗替尼联合程序性死亡受体-1(PD-1)抑制剂治疗晚期胃癌的临床疗效。方法选取医院2021年7月至2023年7月收治的晚期胃癌患者82例,按随机数字表法分为观察组和对照组,各41例。两组患者均予PD-1抑制剂治疗,观察组患者加服盐酸安罗替尼胶囊。两组均以3周为1疗程,连续治疗3个疗程。结果观察组客观有效率及疾病控制率分别为34.15%及73.17%,显著高于对照组的12.20%及46.34%(P<0.05)。观察组患者治疗后癌胚抗原、糖类抗原19-9、糖类抗原242、细胞角蛋白19片段抗原21-1水平均显著低于对照组(P<0.05);血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子、基质金属蛋白酶-9水平均显著低于对照组(P<0.05);CD_(4)^(+)水平及CD_(4)^(+)/CD_(8)^(+)均显著高于对照组,CD_(8)^(+)水平显著低于对照组(P<0.05)。两组各不良反应发生率无显著差异(P>0.05)。结论安罗替尼联合PD-1抑制剂治疗晚期胃癌,能显著改善患者的肿瘤标志物、VEGF及T淋巴细胞水平。

西黄胶囊联合DP方案治疗中晚期非小细胞肺癌的疗效观察

目的:分析西黄胶囊联合多西他赛+顺铂(DP)方案同步放化疗对中晚期非小细胞肺癌(NSCLC)患者客观缓解率及循环肿瘤细胞(CTCs)水平的影响。方法:选取从2019-06-2022-06本院收治的中晚期NSCLC患者156例,按治疗方法的不同分为对照组(DP化疗)和观察组(西黄胶囊联合DP化疗),每组78例。对比两组患者客观缓解率(ORP)、生存质量评分及CTCs水平。结果:治疗后观察组患者ORR高于对照组(P<0.05),CTCs水平低于对照组(P<0.05);治疗后两组生存质量评分(情绪功能、角色功能、躯体功能、认知功能、社会功能、整体生活功能)显著升高,且观察组高于对照组(P<0.05);两组患者不良反应发生率比较差异无统计学意义(P>0.05)。结论:对中晚期NSCLC患者采用西黄胶囊联合DP化疗方案同步治疗效果显著,值得推广应用。

基于ISET技术的晚期胃癌循环肿瘤细胞检测及其临床意义

目的:观察基于ISET分离技术的胃癌晚期患者外周血循环肿瘤细胞(CTCs)的检出情况,探索其与患者临床特征的关系。方法:采用KATOⅢ细胞株进行ISET技术回收率及敏感性测试实验。选取2014年10月至2015年7月在南京大学医学院附属南京鼓楼医院肿瘤科经病理证实的34例胃癌Ⅳ期患者为研究对象,并与15例健康体检者作对照;采集受试者2.5ml静脉血,经CTCBIOPSY异常细胞分离染色仪检测其CTCs阳性率,并分析CTCs与患者临床特征的关系。结果:ISET分离技术的回收率平均值为85.5%,其敏感性为1个/2.5ml。胃癌组CTCs阳性率为23.5%(8/34),对照组均未检出CTCs。CTCs≥4个组与CTCs=0个组AFP、CA199、CA242平均数分别为:6 484.3 vs 102.9ng/ml、4 595.5 vs 683.8U/ml、23 332.1 vs 806.0U/ml,2组比较差异有统计学意义(P=0.021,0.049,0.020)。结论:基于ISET法的CTCs捕获技术具有较高的检出率。胃癌晚期患者外周血CTCs阳性率与患者临床特征具有相关关系。