Clinical Application of Serum Tumor Abnormal Protein (TAP) in Colorectal Cancer Patients

Objective: To explore the association of serum tumor abnormal protein (TAP) with other serologicalbiomarkers e.g. carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen19-9 (CA19-9) and its clinical application in colorectal cancer (CRC) patients. Methods: Patients (N=98) wereenrolled into this study with histologically or cytologically confirmed CRC. Using a test kit, the level of TAPwas determined, while chemiluminescence was used to measure the levels of some other common serologicalbiomarkers e.g. CEA, CA125 and CA19-9. Results: The area of TAP condensed particulate matter decreased afterchemotherapy compared with before chemotherapy when CT or MRI scans showed disease control. In contrast,it increased with disease progression (P<0.05). Furthermore, a statistically significant difference was confirmed inmonitoring of TAP and common serological biomarkers e.g. CEA and CA19-9 (p<0.05). Conclusions: DetectingTAP in CRC patients has high sensitivity and specificity and can be used as a new independent indicator forclinically monitoring CRC patients in the course of chemotherapy.     

Colorectal cancer in pregnancy: a case report and literature review

Colorectal cancer (CRC) in pregnancy is rare. The clinical manifestations of CRC during pregnancy are not specific, and diagnosis and treatment pose a significant challenge. Patients are often found to have advanced tumors, and have a poor prognosis. In this case study, the patient was 36 years old, and had no obvious clinical manifestations in the first and second trimesters. Since gestational week 38, she experienced left upper abdominal pain and constipation, with no nausea or vomiting. Imaging examinations revealed malignant tumors of the sigmoid colon (colon cancer was highly suspected), multiple liver metastases, omental metastases, and multiple swollen lymph nodes in the abdominal cavity. After discussion, the patient received lower cesarean section. A large amount of hematochezia with a volume of approximately 1,000 mL occurred 8 days after the operation. In the emergency department, superior and inferior mesenteric angiography was performed, and the inferior mesenteric artery was continuously pumped with pituitrin to stop bleeding. After the condition was stabilized, she underwent surgery for radical sigmoid resection and colon single-cavity fistula. During the operation, light bloody ascites were observed inside the abdominal pelvis, approximately 500 mL, with multiple touchable stiff metastatic nodules in the liver. At the side of the sigmoid mesocolon, a giant tumor of approximately 12 cm diameter was found, continued by the intestinal wall, and the sigmoid mesocolon was almost occupied by the tumor. The mesentery was hard to recognize, with possible movement of the tumor, and no sign of infiltration into the abdominal pelvic wall or adnexa. The surgical pathological stage was Dukes’ stage D, which was an advanced tumor. Postoperative radiotherapy and chemotherapy were not performed, and the patient died of systemic multiple organ failure 32 days after colon cancer surgery (postpartum day 43). So for patients with digestive system symptoms during pregnancy, CRC should be considered in differential diagnosis. Auxiliary examinations should be actively carried out to strive early diagnosis and treatment to improve patient prognosis.     

人直肠及其癌组织DNA的RAPD多态性分析

目的：研究细胞癌变后DNA结构的改变与寻找与癌变有关的DNA片段，方法：采用AP－PCR方法扩增直肠癌及其癌旁和正常组织DNA，结果：引物E1（5′CGGCCCCTGT3′）对直肠癌，癌旁组织和正常直肠组织的DNA扩增产物的电泳图谱表现出多态性，而且分别得到直肠癌组织特异的DNA片段K851和正常直肠组织特异的DNA片段K1072，K776。结论：直肠细胞癌变后DNA结构在引物E1序列处发生了改变，DNA片段K851，K1072和K776可能与细胞癌变有关。     

Attitudes Towards Colorectal Cancer (CRC) and CRC Screening Tests among Elderly Malay Patients

Background: Colorectal cancer (CRC) is the third most common malignancy in Malaysia, where data arelimited regarding knowledge and barriers in regard to CRC and screening tests. The aim of the study was toassess these parameters among Malaysians. Materials and Methods: The questionnaires were distributed inthe Umra Private Hospital in Selangor. The questionnaire had four parts and covered social-demographicquestions, respondent knowledge about CRC and colorectal tests, attitude towards CRC and respondentactionregarding CRC. More than half of Malay participants (total n=187) were female (57.2%) and 36.9% of themwere working as professionals. Results: The majority of the participants (93.6%) never had a CRC screeningtest. The study found that only 10.2% of the study participants did not consider that their chances of gettingCRC were high. A high percentage of the participants (43.3%) believed that they would have good chance ofsurvival if the cancer would be found early. About one third of the respondents did not want to do screeningbecause of fear of cancer, and concerns of embarrassment during the procedure adversely affected attitude toCRC screening as well. Age, gender, income, family history of CRC, vegetable intake and physical activity werefound to be significant determinants of knowledge on CRC. Conclusions: The major barriers identified towardsCRC screening identified in our study were fear of pain and embarrassment. The findings have implicationsfor understanding of similarities and differences in attitude to CRC amongst elderly patients in other cultural/geographic regions.     

结直肠癌中miR-31的表达及预测靶基因的生物信息学分析

目的 检测microRNA-31（miR-31）在结直肠癌中的表达及功能,预测其靶基因并进行生物信息学分析,为研究其作用和调控机制奠定基础。方法 采用实时荧光定量反转录聚合酶链反应（qRT-PCR）检测8种结肠癌细胞株、40例结直肠癌（colorectal cancer, CRC）患者癌组织及匹配的正常黏膜组织及33例结直肠腺瘤组织中miR-31的表达情况,并分析癌组织中miR-31表达与患者临床特征的关系。MTS法观察转染miR-31模拟物（mimics）组、抑制剂（inhibitor）组和对照组（miRControl）及空白细胞组细胞生长的差异,Western blot检测空白细胞组、miR-31 mimics和inhibitor三组细胞PCNA蛋白的表达。TargetScan、DIANA-microT、miRanda等软件预测miR-31的靶基因,并进行KEGG功能和信号通路富集分析。结果 miR-31在8种结肠癌细胞株中高表达,同时CRC患者癌组织中的表达高于腺瘤及正常黏膜组织（P<0.05）。其中癌组织和匹配的正常黏膜相比,miR-31表达明显上调（P=0.035）,但腺瘤和正常黏膜相比,差异无统计学意义（t=0.122, P=0.904）。miR-31的表达与临床病理特征间未见明显关系（P均＞0.05）。转染miR-31 mimics后,miR-31的表达明显上调且和miR-Control组及空白细胞组相比,miR-31 mimics组细胞生长加快;而转染miR-31 inhibitor组miR-31表达显著降低,细胞生长活力明显受抑制。同时转染miR-31 inhibitor组PCNA蛋白表达较miR-31 mimics组和空白细胞组显著降低。生物信息学分析miR-31靶基因功能集中于转录后及翻译水平的调节、细胞连接、迁移及细胞运动等生物学过程。信号通路主要富集于内吞作用、轴突导向、T细胞受体信号通路、Wnt及MAPK信号通路。结论 miR-31在结直肠癌中高表达,且miR-31可以促进细胞生长和增殖,其靶基因可能通过调节多种生物学过程发挥作用。     

结直肠癌患者组织与粪便中K—ras癌基因12位点突变的分析

目的：探讨直肠癌（CRC）患者的组织与粪便中K-ras癌基因12位点突变检测结果的联系及检出率差异,为建立结直肠癌早期筛检方法提供科学依据。方法：应用聚合酶链反应－限制性片段长度多态性分析（PCR－RFLP）方法对45例原发性结直肠癌患者手术切除的组织及术前粪便标本中K-ras癌基因12位点的突变情况进行检测,结果采用卡方检验及卡伯值（Kappa value)进行统计分析。结果：癌组织、远端手术切缘粘膜、粪便标本中的K-ras癌基因12位点突变检出率分别为35．56％（16／45）、4．44％（2／45）、37．78％（17／45）。癌组织与粪便标本检测结果的关联检验为：X^2=33．09,P＜0．01;差别检验为：X^2=0,P＞0．05;观察一致率为93．33％,卡柏值为0．86。结论：粪便中K-ras癌基因12位点突变检测结果与癌组织的检测结果存在联系,其检出率无显著性差异,可靠性极好;且粪便取材方便,无创伤性,可能作为结直肠癌高危人群的筛检方法。     

维生素D3与结直肠癌相关性的研究进展

越来越多的研究证据已经表明,血清中低水平的维生素D₃（VD₃）与较高的结直肠癌（CRC）风险相关。目前大多数的观察性研究支持血清中25-(OH)-VD₃水平与CRC风险呈负相关性。然而,口服VD3或饮食中补充VD₃可否改善CRC患者的总生存期,目前还存在争议。本文将对近年来VD₃与CRC相关性的研究作一综述,以期有更多前瞻性的基础研究、临床研究和人群观察性研究对VD3是否对CRC的预防和治疗有价值做出澄清。     

肿瘤相关成纤维细胞在结直肠癌发生发展中的作用研究进展

肿瘤相关成纤维细胞（CAFs）是间质的主要细胞成分,在结直肠癌（colorectal cancer,CRC）的发生发展中发挥重要作用。CAFs通过细胞与细胞间的直接接触以及旁分泌的方式分泌各种细胞因子、生长因子和趋化因子,通过不同的信号通路促进CRC的发生、生长以及血管生成、侵袭和转移。CAFs还为CRC的早期诊断和治疗提供新的标记和新的靶点,为CRC的综合治疗提供新的思路。本文主要就近年来CAFs在结直肠癌发生发展以及诊治中作用的研究进展作一综述。     

FHIT基因及错配修复基因MLH1在结直肠癌中的表达研究

目的　探讨FHIT、MLH 1基因在结直肠癌组织中的表达及其意义。方法　采用免疫组化S P法检测 84例结直肠癌组织中FHIT、MLH 1基因表达。结果　FHIT、MLH 1基因在 84例结直肠癌中表达阳性率分别为 48.81%和 92 .86%。FHIT基因水平低或不表达与患者年龄、性别、肿瘤部位、组织学类型无关 (P >0 .0 5 ) ,而与肿瘤浸润深度、分化程度、Dukes分期和淋巴结转移有关 (P <0 .0 5 ) ;结直肠癌组织中FHIT基因表达与MLH 1基因表达无显著相关性 (P >0 .0 5 )。结论　FHIT基因参与了结直肠癌的演化和进展 ,是结直肠癌的 1个候选抑癌基因 ;结直肠癌组织中FHIT、MLH 1基因表达的关系还有待深入研究     

载脂蛋白E对结直肠癌细胞侵袭迁移能力的影响

目的 观察载脂蛋白E（apolipoprotein E, ApoE）对结直肠癌细胞侵袭迁移能力的影响。方法 在结直肠癌细胞系SW48中转染ApoE过表达质粒及其特异性siRNA,实时荧光定量PCR（Real timeqPCR）检测转染ApoE的表达,利用Transwell小室观察ApoE对细胞侵袭迁移能力的影响,通过免疫印迹检测ApoE对基质金属蛋白酶（matrix metalloproteinase, MMP）家族蛋白表达的影响。结果 RTPCR检测结果显示：过表达ApoE组细胞中ApoE mRNA水平显著高于空白对照白组和阴性对照组,差异有统计学意义（P=0.008）,ApoE沉默组中ApoE mRNA水平与阴性对照组比,差异有统计学意义（P=0.013）;Transwell侵袭实验结果显示,穿膜细胞数：空白对照组、阴性对照组、过表达ApoE组、si-ApoE组依次为：（209±17）、（228±11）、（67±9）、（428±15）个/视野,过表达ApoE组和si-ApoE组与阴性对照组相比,差异有统计学意义（P<0.05）;Transwell迁移实验结果显示,空白对照组（326±18）个/视野,阴性对照组（338±21）个/视野,过表达ApoE组（133±11）个/视野,与阴性对照组相比,差异有统计学意义（P<0.05）,si-ApoE组（518±13）个/视野与阴性对照组相比,差异有统计学意义（P<0.05）。同时免疫印迹实验显示,过表达ApoE组细胞中MMP-2及MMP-9的表达下降,组织基质金属蛋白酶抑制剂2（tissue inhibitors of metalloproteinase-2, TIMP-2）的表达升高,而si-ApoE组MMP-2及MMP-9表达升高,TIMP-2的表达降低。结论 ApoE可影响结直肠癌细胞的侵袭、迁移能力,并且可能通过影响TIMP-2、MMP-2及MMP-9的表达发挥上述功能。     

HER-2在结直肠癌组织中的表达及其临床意义

目的研究人类表皮生长因子受体-2(human epidermal growth factor receptor 2,HER-2)在结直肠癌组织中的表达及特征。方法运用免疫组化的方法检测经外科手术切除的50例结直肠癌组织标本和30例正常结直肠组织标本中HER-2的表达状况,并研究HER-2表达与结直肠癌病理特征和临床表现的相关性。结果 HER-2在结直肠癌组织中表达阳性18例(36.0%),正常组织阳性3例(10.0%),2组差异有统计学意义(P<0.05)。HER-2基因表达与结直肠癌患者的年龄、部位及性别等无关(P>0.05),但是与结直肠癌的分期、患者淋巴结转移等有着明显的相关性(P<0.05)。HER-2阳性的结直肠癌患者5年生存率显著低于阴性患者(P<0.05)。结论结直肠癌患者中存在HER-2蛋白过表达,HER-2或成为结直肠癌的一种早期检测和诊断标志物。     

HER-2基因和基质金属蛋白酶-9在大肠癌中的表达和临床意义

目的探讨HER-2和基质金属蛋白酶-9在大肠癌中的表达及其临床意义。方法采用Elivision免疫组化检测法，用HER-2抗体、MMP-9抗体标记50例大肠癌组织标本。综合考虑切片中阳性细胞占所观察同类细胞的百分比和阳性细胞着色强度来判断。结果MMP-9、HER-2表达与大肠癌患者性别、年龄、肿瘤部位无相关性，（P〉0．05）。DukesC期、DukesD期患者中MMP-9、HER-2阳性表达率明显高于DukesA期、DukesB期，（P〈0．05）。大肠癌A型血患者中MMP-9、HER-2阳性率明显高于非A型血患者，（P〈0．05）。但HER-2与MMP-9表达间无协同作用。结论MMP-9、HER-2的表达均是反映大肠癌侵袭、转移的重要标记物，它们独自影响和调节大肠癌侵袭和转移。     

Detection of Human Cytomegalovirus in patients with Colorectal Cancer by Nested-PCR

Background: The association of colorectal cancer with human cytomegalovirus (HCMV) is a controversial issuein cancer research. This study aimed to identify the HCMV virus in colorectal cancer tissues and to investigatethe association of HCMV with colorectal cancer. In this study, 50 cancer tissue samples and 50 samples withoutcolon cancer were studied in order to identify the HCMV virus through nested-polymerase chain reaction. Thevirus was identified in 15 cases of colorectal cancer tissues (15/50) and in 5 cases of normal tissues (5/50). Eightcases of adenocarcinoma tissues were in a moderately differentiated stage, and 7 cases had well-differentiatedstage tissues that were positive for viral DNA. The findings were statistically evaluated at a significance levelof p<0.05. The HCMV virus could play a role in creating malignancy and the progress of cancer through theprocess of oncomodulation.     

HPV16型感染与结直肠癌临床病理特征和预后关系的研究

 目的　探讨HPV16型DNA与结直肠癌临床病理和预后的关系。方法　结直肠癌50例、腺瘤38例和正常结直肠粘膜组织20例,应用多聚酶链反应(PCR)检测HPV16型DNA序列,并对其扩增产物进行电泳分析和southern blot分析。追踪观察患者的预后。结果　三组患者HPV16型DNA阳性率分别为42%、31.6%和0。结直肠癌和腺瘤分别与正常大肠粘膜组织比较,HPV16型DNA阳性率有显著性差异(P<0.05);结直肠癌和腺瘤之间比较,HPV16型DNA阳性率无显著性差异(P>0.05)。HPV16型DNA阳性与结直肠癌患者的年龄、性别,以及肿瘤的部位、大小、组织类型、临床分期均无关,但与其预后有关。结论　HPV16型感染是影响结直肠癌预后的因素之一。     

结直肠癌组织中Krüppel样因子17的表达及其与预后的关系

目的 研究Krüppel样因子17(Krüppel-like factor 17, KLF17)在结直肠癌组织中的表达及其与患者临床病理特征及预后的关系。方法 收集武汉市第一医院128例结直肠癌患者的临床病理资料,采用免疫组织化学法检测KLF17在结直肠癌及对应的非癌结直肠黏膜组织中的表达,Kaplan-Meier法绘制生存曲线,Cox比例风险模型进行生存分析。结果 128例结直肠癌中,83例癌组织存在KLF17低表达。KLF17低表达与结直肠癌患者淋巴结转移相关（P=0.012）。KLF17低表达患者5年无病生存率及总生存率分别为46.3%和49.3%,明显低于KLF17高表达患者的78.3%和82.0%（P均=0.001）。Cox 模型分析结果显示：KLF17、术前肠梗阻、肿瘤分化程度和病理学N分期是结直肠癌患者无病生存时间及总生存时间的独立预后因素（P均＜0.05）。结论 KLF17低表达与结直肠癌淋巴结转移相关,是结直肠癌患者预后不良的一个潜在分子指标。     

应用 PCR 方法检测大肠癌组织中的 HPV DNA

本文采用聚合酶链式反应（ＰＣＲ）的方法，对２０例大肠癌患者的手术切除标本进行了人体乳头瘤病毒（ＨＰＶ）ＤＮＡ的检测。结果发现４例（２０％）ＨＰＶ１６型扩增阳性，其中１例显示ＨＰＶ１６．１８型双重阳性。初步表明大肠癌组织中存在ＨＰＶ的感染。     

人乳头瘤病毒检测对宫颈病变的诊断价值

目的：比较分析阴道镜活检与人乳头瘤病毒（ HPV）检测对宫颈病变诊断的临床应用价值。方法选取接受宫颈病变筛查的2560例已婚妇女为研究对象,其中行阴道镜活检560例,行HPV检测2000例,对两组检查结果进行对比分析。结果560例妇女阴道镜活检HPV阳性率为44．46％,2000例妇女HPV检测HPV阳性率为42．55％,两组比较差异无统计学意义,P＞0．05。经后期确认,上述患者中宫颈囊肿患者180例,阴道镜活检检出172例,漏诊8例,漏诊率为4．44％;HPV检测检出102例,漏诊78例,漏诊率为43．33％,阴道镜活检的漏诊率明显低于HPV检测,P＜0．01,差异具有统计学意义。结论阴道镜活检与HPV检测在宫颈病变诊断中均有良好效果,根据具体情况选择合适的检测方式。     

Changes of TCR repertoire diversity in colorectal cancer after Erbitux (cetuximab) in combination with chemotherapy

We have previous found a positive correlation between post-therapy TCR repertoire normalization and remission of colorectal cancer (CRC) patients following fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus bevacizumab or Rh-endostatin therapy. To further define the TCR repertoire diversity changes following treatment in CRC patients, and confirm its potential prognostic value, the present study extended the sample size of follow-up and used an alternative therapy regime to investigate changes of TCR repertoires following Erbitux plus FOLFIRI therapy. Inclusion and exclusion criteria have been established to screen out 26 patients to receive Erbitux plus FOLFIRI therapy. Efficacy and toxicity assessment have been made for them after 3 months’ treatment as well as the TCR repertoire diversity has been determined. A CDR3 complex scoring system was used to quantify the diversity of TCR repertoire. The results showing that the diversity of CD4⁺ T cells in PR group was significantly higher than that of SD and PD groups, and the difference was enlargement after treatment. The diversity of CD8⁺ T cells in PR group has no difference before and after treatment, but significant decrease in SD and PD group after treatment. In conclusion, analysis the diversity of T cell repertoire has an important prognosis value for CRC patients.     

Tumor-Derived Matrix Metalloproteinase-13 (MMP-13) Expression in Benign and Malignant Breast Lesions

Introduction: Breast carcinoma is the most common malignancy and the leading cause of cancer death in women. Matrix metalloproteinase-13 (MMP-13) is a hypothetical prognostic marker in invasive breast cancer. This study aimed to determine MMP-13 expression in benign and malignant breast lesions and to evaluate the correlation between MMP-13 expression and tumor characteristics in invasive ductal carcinoma (IDC). Materials and Method: We evaluated cytoplasmic expression of MMP-13 based on staining index using immunohistochemistry (IHC) in epithelial cells, stromal fibroblasts of IDC (n=90) and benign epithelial breast (n=90) lesions. Correlation between IHC and tumor size, lymph node status, distance metastasis, estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu was assessed. Results: MMP-13 expression was 45% and 38.8% in malignant epithelial cells and peritumoral fibroblasts, respectively. Only low level of MMP-13 expression was seen in benign breast lesions (8.8% in epithelial component and 2.2% in stromal fibroblasts), while high level of MMP-13 expression was noted in malignant tumors, mainly grade II or III. Cytoplasmic MMP-13 expressions in epithelial tumor cells was correlated significantly with peritumoral fibroblasts. MMP-13 expression was directly correlated with distant metastasis and tumor stage in epithelial tumoral cells and was inversely correlated with progesterone expression in both tumoral and stromal cells. Conclusion: This study showed that MMP-13 was a moderator for tumor invasion and metastasis and could be an independent predictor of poor prognosis in breast cancer. The role of MMP-13 in predicting the risk of malignant transformation in benign lesions should be further investigated.     

A cross-sectional study of obstructive sleep apnea in patients with colorectal cancer

BackgroundThe association between colorectal cancer (CRC) and obstructive sleep apnoea (OSA) has been attracting increasing attention. several studies had confirmed that OSA increases the risk of CRC onset. However, the findings of studies on the morbidity of OSA in patients with CRC were unclear. Therefore, this study aimed to investigate the morbidity of OSA in patients with CRC as well as the association between the clinicopathological characteristics of OSA and CRC.MethodsA total of 414 patients with a pathological diagnosis of CRC from 1 January, 2020 to 30 December, 2020 were included in this study. Demographic characteristics, clinical information, and tumor characteristics of participants were collected; sleep was monitored using a wearable oximeter and via sleep quality questionnaire. The oxygen desaturation index (ODI) was used to classify OSA severity so that the diagnostic criteria for OSA were set based on the ODI as 0–5 (normal) and ≥5 (abnormal). After correcting for confounding factors, a logistic regression analysis was performed to calculate the odds ratio (OR) and 95% confidence interval (CI) for the factors affecting the tumor lymph node stage (N stage).ResultsA total of 402 patients with CRC were included in this study, including 225 (55.97%) men and 177 (44.03%) women. The mean ODI value of participants was 3.40±8.17. The morbidity of OSA among the patients with CRC having ODI ≥5 was 16.17%. A comparison between the normal and abnormal ODI value groups revealed that the high proportion of abnormal ODI was related to higher N stage (P<0.05). Logistic regression analysis revealed a correlation of ODI values and age to the N stage. Specifically, CRC patients with an abnormal ODI had a higher risk of lymph node metastasis compared to those with normal ODI (OR =1.915, 95% CI: 1.025 to 3.579). Moreover, patients with CRC aged ≥65 years had a higher risk of lymph node metastasis compared to those aged <65 years (OR =2.190, 95% CI: 1.163 to 4.125).ConclusionsCRC patients with abnormal ODI are susceptible to OSA. Additionally, abnormal ODI and age ≥65 years are relevant factors for the N2 stage.