Gefitinib improves severe bronchorrhea and prolongs the survival of a patient with lung invasive mucinous adenocarcinoma:A case report

BACKGROUND Lung invasive mucinous adenocarcinoma(LIMA),formerly referred to as mucinous bronchioloalveolar carcinoma,is a rare disease that usually presents as bilateral lung infiltration,is unsuitable for surgery and radiotherapy,and shows poor response to conventional chemotherapy.CASE SUMMARY We report a 56-year-old Chinese man with a history of smoking and epidermal growth factor receptor mutation-positivity who was initially misdiagnosed as severe pneumonia,but was ultimately diagnosed as a case of invasive mucinous adenocarcinoma of the lung by computed tomography-guided percutaneous lung biopsy.Bronchorrhea and dyspnea were improved within 24 h after initiation of gefitinib therapy and the radiographic signs of bilateral lung consolidation showed visible improvement within 30 d.After more than 11 months of treatment,there is no evidence of recurrence or severe adverse events.CONCLUSION Although the precise mechanism of the antitumor effects of gefitinib are not clear,our experience indicates an important role of the drug in LIMA and provides a reference for the diagnosis and treatment of this disease.

Minimally invasive surgery for gastro-oesophageal junction adenocarcinoma: Current evidence and future perspectives

Minimally invasive surgery is increasingly indicated in the management of malignant disease.Although oesophagectomy is a difficult operation,with a long learning curve,there is actually a shift towards the laparoscopic/thoracoscopic/robotic approach,due to the advantages of visualization,surgeon comfort(robotic surgery)and the possibility of the whole team to see the operation as well as and the operating surgeon.Although currently there are still many controversial topics,about the surgical treatment of patients with gastro-oesophageal junction(GOJ)adenocarcinoma,such as the type of open or minimally invasive surgical approach,the type of oesophago-gastric resection,the type of lymph node dissection and others,the minimally invasive approach has proven to be a way to reduce postoperative complications of resection,especially by decreasing pulmonary complications.The implementation of new technologies allowed the widening of the range of indications for this type of surgical approach.The short-term and long-term results,as well as the benefits for the patient-reduced surgical trauma,quick and easy recovery-offer this type of surgical treatment the premises for future development.This article reviews the updates and perspectives on the minimally invasive approach for GOJ adenocarcinoma.

Extramammary Paget’s Disease Manifested by Intraepithelial Adenocarcinoma of the Vulva and Anus Combined with Invasive Adenocarcinoma of the Ampullary Part of the Rectum

The Object of the Study: The author of the given paper describes an unusual combination of two diseases: extramammary Paget’s disease manifested by intraepithelial adenocarcinoma of the vulva and anus combined with invasive adenocarcinoma of the ampullary part of the rectum and describes the atypical manifestations of these diseases. The Content: The content of this research paper includes a description of the patient, an analysis of the clinical picture, diagnostic methods and therapeutic interventions used, a report of the following disease, and the result of the presented case. The Result of the Research Work: The result of the research work is the analysis of a clinical case with two different tumors, where such a combination of tumors is rarely described in the literature. Moreover, no large specific sample with this combination of diseases is available. Patient Characteristics: The given case report describes a patient of the Palliative Care Unit of the Gerontology Clinic with a primary diagnosis of C20-rectal adenocarcinoma in the background of the anal canal, perineal skin Paget’s disease, stage IV. The presented complications of the patient’s primary diagnosis are multiple metastases in the liver;status post palliative chemotherapy;hepatomegaly;metastases to abdominal lymph nodes, inguinal lymph nodes;metastases at Th12, L4 level;pain syndrome. The presented above combination of diagnosed diseases is very rare. Applied Diagnostics: In October 2021, it was performed diagnostic manipulation: biopsy and the pathologist have provided a microscopic description. The first tissue fragment had a pronounced electrothermal lesion and the epithelial structures were not valuable. The second skin tissue fragment was covered with hyperplastic and acanthotic epithelium;its basal and middle layers contained multiple large cells proliferates extending into the medial epidermis, and the cytoplasm of these cells reacted positively with PAS (Periodic Acid Schiff reaction). It needs to be noted that the patient had previously had several years of biopsies from the perineal and anal epidermis, where Paget’s disease had also been diagnosed. The performed immunohistochemistry showed these cells to be CK20 positive, CK7 rare positive and p16 negative. The following pathohistological findings were made: morphological and immunohistochemical picture is consistent with Paget’s disease. According to the ICD-10, the patient was diagnosed with C51 malignant neoplasm of the female external genitalia. Using imaging diagnostics, it became clear that the patient’s rectal adenocarcinoma had progressed to metastatic stage with distant liver metastases in the background of anal canal, perineal skin Paget’s disease. Therapeutic Plan of the Patient: Based on the patient’s main diagnoses, the complications of the principal diagnosis, the patient’s overall severe condition, pain syndrome, age and comorbidities, palliative chemotherapy was approved as a therapeutic option in council of doctors. Monitoring and Outcome of the Patient: The patient’s general condition was becoming worse over time, and she was diagnosed with exitus latalis in December 2022. At that time, the patient was discharged from hospital and was on palliative care at home under the control of her family physician.

Low-depth whole genome sequencing reveals copy number variations associated with higher pathologic grading and more aggressive subtypes of lung non-mucinous adenocarcinoma

Objective:Histology grade,subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival.The aim of the study was to investigate the relationship between chromosomal instability,morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma(LNMA).Methods:We developed a whole genome copy number variation(WGCNV)scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples.Results:Higher histological grades,aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score,particularly in CNV regions enriched for tumor suppressor genes and oncogenes.In addition,we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types(<100 cells)isolated by sample laser capture microdissection.Conclusions:Our findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.

Characterization of the highly invasive subline of the human rectal adenocarcinoma in vitro

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Large-duct pattern invasive adenocarcinoma of the pancreas–a variant mimicking pancreatic cystic neoplasms: A minireview

Pancreatic cancer currently has no subtypes that inform clinical decisions;hence,there exists an opportunity to rearrange the morphological and molecular taxonomy that guides a better understanding of tumor characteristics.Nonetheless,accumulating studies to date have revealed the large-duct type variant,a unique subtype of pancreatic ductal adenocarcinoma(PDA)with cystic features.This subtype often radiographically mimics intraductal papillary mucinous neoplasms(IPMNs)and involves multiple small cysts occasionally associated with solid masses.The“bunch-of-grapes”sign,an imaging characteristic of IPMNs,is absent in large-duct PDA.Large-duct PDA defines the mucin profile,and genetic alterations are useful in distinguishing large-duct PDA from IPMNs.Histologically,neoplastic ducts measure over 0.5 mm,forming large ductal elements.Similar to classic PDAs,this subtype is frequently accompanied by perineural invasion and abundant desmoplastic reactions,and KRAS mutations in codon 12 are nearly ubiquitous.Despite such morphological similarities with IPMNs,the prognosis of large-duct PDA is equivalent to that of classic PDA.Differential diagnosis is therefore essential.

Contemporary review of minimally invasive pancreaticoduodenectomy

AIM To assess the current literature describing various minimally invasive techniques for and to review short-term outcomes after minimally invasive pancreaticoduodenectomy(PD). METHODS PD remains the only potentially curative treatment for periampullary malignancies, including, most commonly, pancreatic adenocarcinoma. Minimally invasive approaches to this complex operation have begun to be increasingly reported in the literature and are purported by some to reduce the historically high morbidity of PD associated with the open technique. In this systematic review, we have searched the literature for high-quality publications describing minimally invasive techniques for PD-including laparoscopic, robotic, and laparoscopicassisted robotic approaches(hybrid approach). We have identified publications with the largest operative experiences from well-known centers of excellence for this complex procedure. We report primarily short term operative and perioperative results and some short term oncologic endpoints. RESULTS Minimal y invasive techniques include laparoscopic, robotic and hybrid approaches and each of these techniques has strong advocates. Consistently, across all minimally invasive modalities, these techniques are associated less intraoperative blood loss than traditional open PD(OPD), but in exchange for longer operating times. These techniques are relatively equivalent in terms of perioperative morbidity and short term oncologic outcomes. Importantly, pancreatic fistula rate appears to be comparable in most minimally invasive series compared to open technique. Impact of minimally invasive technique on length of stay is mixed compared to some traditional open series. A few series have suggestedthat initiation of and time to adjuvant therapy may be improved with minimally invasive techniques, however this assertion remains controversial. In terms of shortterms costs, minimally invasive PD is significantly higher than that of OPD. CONCLUSION Minimally invasive approaches to PD show great promise as a strategy to improve short-term outcomes in patients undergoing PD, but the best results remain isolated to high-volume centers of excellence.

Relationship between cachexia and perineural invasion in pancreatic adenocarcinoma

BACKGROUND Cachexia is responsible for the low quality of life in pancreatic adenocarcinoma(PDAC).The rapid disease progression and patient deterioration seems related to perineural invasion,but the relationship between cachexia and perineural invasion for the evolution of the disease has been rarely studied.As perineural invasion is difficult to be highlighted,a biomarker such as the neurotrophic factor Midkine(MK)which promotes the neuronal differentiation and the cell migration could be helpful.Also,Activin(ACV)has been described as cachexia related to PDAC.However,their role for assessing and predicting the disease course in daily practice is not known.AIM To assess the relationship between perineural invasion and cachexia and their biomarkers,MK and ACV,respectively,and their prognostic value.METHODS This study included prospectively enrolled patients with proven adenocarcinoma and a matched group of controls without any malignancies.Patients with other causes of malnutrition were excluded.The plasma levels of ACV and MK were analyzed using western blotting and were correlated with the clinicopathological features and survival data.These results were validated by immunohistochemical analyses of the pancreatic tumor tissue of the patients included in the study and a supplementary group of surgically resected specimens from patients with a benign disease.RESULTS The study comprised 114 patients with PDAC,125 controls and a supplementary group of 14 benign pancreatic tissue samples.ACV and MK were both overexpressed more frequently in the plasma of patients with PDAC than in the controls(63% vs 32% for ACV,P<0.001;47%vs 16%for MK,P<0.001),with similar levels in pancreatic tissue the MK protein expression was closely related to the advanced clinical stage(P=0.006),the presence of metastasis(P=0.04),perineural invasion(P=0.03)and diabetes(P=0.002),but with no influence on survival.No correlation between clinicopathological factors and ACV expression was noted.Cachexia,present in 19%of patients,was unrelated to ACV or MK level.Higher ACV expression was associated with a shorter survival(P=0.008).CONCLUSION The MK was a biomarker of perineural invasion,associated with tumor stage and diabetes,but without prognostic value as ACV.Cachexia was unrelated to perineural invasion,ACV level or survival.

INVASION OF SPHEROID OF MURINE LUNG ADENOCARCINOMA (LA_(795)) CELLS INTO EMBRYONIC CHICK HEART FRAGMENTS

An in vitro spheriod invasion model of tumor cell was established by using murine lung adenocarcinoma cell line (LA795) and precultured embryonic chick heart fragment (PHF). The spheroid of LA795 cells were prepared by incubating a suspension of trypsinized LA795 cells on a gyratory shaker. Spheroid aggregates of LA795 cells in diameter of 0. 2 mm were selected and confronted with PHF (diameter of 0. 4 mm) on semi- solid medium for 3 - 4 hours, then, individual confronting pain were transferred into fluid medium for further co-culture on gyratory shaker. After 1, 3, 5 and 7 days, multiple confronting pairs were processed for histological and ultrastructural study. The Invasive capacity and the invasion process of LA795 cells were examined and observed. The results demonstrated that LA795 cell line has a high capacity of invasion and high malignancy in vitro. This spheroid Invasion model is very useful for studying mechanism of Invasiveness of tumor cells in vitro.

Robotic versus laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma: A propensity score-matched analysis

Background: Minimally invasive surgery is becoming increasingly popular in the field of pancreatic surgery. However, there are few studies of robotic distal pancreatectomy(RDP) for pancreatic ductal adenocarcinoma(PDAC). This study aimed to investigate the efficacy and feasibility of RDP for PDAC. Methods: Patients who underwent RDP or laparoscopic distal pancreatectomy(LDP) for PDAC between January 2015 and September 2020 were reviewed. Propensity score matching analyses were performed. Results: Of the 335 patients included in the study, 24 underwent RDP and 311 underwent LDP. A total of 21 RDP patients were matched 1:1 with LDP patients. RDP was associated with longer operative time(209.7 vs. 163.2 min;P = 0.003), lower open conversion rate(0% vs. 4.8%;P < 0.001), higher cost(15 722 vs. 12 699 dollars;P = 0.003), and a higher rate of achievement of an R0 resection margin(90.5% vs. 61.9%;P = 0.042). However, postoperative pancreatic fistula grade B or C showed no significant intergroup difference(9.5% vs. 9.5%). The median disease-free survival(34.5 vs. 17.3 months;P = 0.588) and overall survival(37.7 vs. 21.9 months;P = 0.171) were comparable between the groups. Conclusions: RDP is associated with longer operative time, a higher cost of surgery, and a higher likelihood of achieving R0 margins than LDP.

Vascular resections in minimally invasive surgery for pancreatic cancer

Pancreatic ductal adenocarcinoma(PDAC)is characterised by poor oncological outcome and is the seventh cause of cancer-related deaths worldwide.With the advances in surgical technology,oncological treatment,and critical care,extended pancreatic resections including vascular resections have become more frequently performed in specialised centres.Furthermore,the boundaries of resectability continue to be pushed in order to achieve a potentially curative approach in selected patients in combination with neoadjuvant and adjuvant treatment strategies.This review gives an overview on the current state of venous and arterial resections in PDAC surgery with particular attention given to the minimally invasive approach.

Correlation between Gli2, FAK expression in colonic adenocarcinoma tissue with different clinical pathological characteristics and cancer cell proliferation, invasion

Objective:To study the correlation between glioma-associated oncogene homologue 2 (Gli2), focal adhesion kinase (FAK) expression in colonic adenocarcinoma tissue with different clinical pathological characteristics and cancer cell proliferation, invasion.Methods: 56 patients with colonic adenocarcinoma who received surgical resection in our hospital between May 2012 and December 2015 were selected, cancer tissue and para-carcinoma tissue were collected respectively, immunohistochemical staining was used to detect the Gli2 and FAK protein-positive rate, and fluorescence quantitative PCR was used to determine the mRNA expression of Gli2 and FAK as well as the proliferation and invasionn genes.Results:Gli2 and FAK mRNA expression and protein-positive rate in colonic adenocarcinoma tissues were significantly higher than those in para-carcinoma tissues (P<0.05);Gli2 and FAK mRNA expression and protein-positive rate in colonic adenocarcinoma tissues with low differentiation, no differentiation, extraserosal infiltration and Dukes stage D were significantly higher than those in colonic adenocarcinoma tissues with high differentiation, medium differentiation, intraserosal infiltration, Dukes stage B-C (P<0.05);CyclinD1, CDK4, c-myc, N-cadherin and vimentin mRNA expression in Gli2- and FAK-positive colonic adenocarcinoma tissues were significantly higher than those in Gli2- and FAK-negative colonic adenocarcinoma tissues (P<0.05).Conclusions:Gli2 and FAK expression are high in colonic adenocarcinoma tissues and associated with the clinical pathological staging of tumor, and highly expressed Gli2 and FAK can promote cell proliferation and invasion.

肺浸润性腺癌伴纵隔淋巴结转移性NUT中线癌1例报告及文献复习

目的:分析1例肺浸润性腺癌伴纵隔淋巴结转移性睾丸核蛋白(NUT)中线癌患者的病理诊断过程,为该病的临床诊断提供依据。方法:收集1例肺浸润性腺癌伴纵隔淋巴结转移性NUT中线癌患者的临床资料,术中送检肺肿物行冰冻快速病理诊断以判断病变性质,术后另送纵隔肿瘤行慢病理检测,肺及纵隔肿物均行常规病理检查和免疫组织化学染色,结合相关文献分析该病的病理诊断过程,并进行病理鉴别。结果:患者,男性,59岁,于外院行CT检查见前纵隔软组织密度影和右肺下叶磨玻璃样结节影,均考虑肿瘤性病变。术中肺肿物快速病理诊断考虑肺浸润性腺癌,术后经免疫组织化学染色证实为肺原发性浸润性腺癌。术后另送纵隔肿物,经免疫组织化学染色、院外会诊及基因检测最终证实为淋巴结转移性NUT中线癌。结论:NUT中线癌是罕见的低分化鳞状细胞癌,常发生于中线部位,可伴发其他器官肿瘤并发生淋巴结转移,其确诊需要结合组织学形态、影像学资料和基因检测结果。

中性粒细胞源性外泌体促进肺腺癌细胞的迁移和侵袭

目的研究中性粒细胞源性外泌体对肺腺癌细胞迁移和侵袭的影响。方法采用1μmol/L全反式维甲酸(ATRA)诱导人早幼粒细胞白血病NB4细胞分化成中性粒细胞,MGG染色分析其形态学的改变,流式细胞技术检测其表面标志物CD11b及CD18的表达。采用总外泌体试剂盒分离提取NB4细胞和中性粒细胞来源的外泌体,利用透射电镜技术鉴定外泌体的形态与大小。通过细胞划痕和Transwell迁移实验分析NB4细胞和中性粒细胞来源的外泌体对A549细胞迁移能力的影响。采用Transwell侵袭实验研究NB4细胞和中性粒细胞来源的外泌体对A549细胞侵袭能力的影响。结果MGG染色结果显示NB4细胞经ATRA诱导后分化成中性粒细胞,且流式细胞检测结果表明中性粒细胞表面标志物CD11b及CD18表达明显升高。电镜下观察到NB4细胞和中性粒细胞来源的外泌体大小为40~100 nm,形态呈双层膜,中空,圆形或椭圆形。细胞划痕和Transwell实验证实,中性粒细胞源性外泌体比NB4细胞源性外泌体能更明显地增强肺腺癌细胞的迁移和侵袭能力。结论中性粒细胞源性外泌体能明显促进肺腺癌细胞的迁移和侵袭,参与肺腺癌的发生发展。

LncRNA MALAT1通过靶向miR-146a调节PI3K/Akt信号通路影响胃癌细胞的增殖、迁移和侵袭

目的 探究长链非编码RNA(long non-coding RNA,LncRNA)肺腺癌转移相关转录子1(metastasis-associated lung adenocarcinoma transcript 1,MALAT1)通过调节miR-146a对胃癌(gastric cancer, GC)细胞的增殖、迁移和侵袭的影响及其机制。方法 收集GC组织和配对正常胃上皮组织,将GC细胞MNK-45分为空白对照(blank control, BC)组(未转染)、MALAT1 siRNA-NC组(转染MALAT1 siRNA-NC)、MALAT1 siRNA组(转染MALAT1 siRNA)、miR-146a mimics-NC组(转染miR-146a mimics-NC)、miR-146a mimics组(转染miR-146a mimics)、MALAT1 siRNA+miR-146a inhibitor-NC组(共转染MALAT1 siRNA+miR-146a inhibitor-NC)、MALAT1 siRNA+miR-146a inhibitor组(共转染MALAT1 siRNA+miR-146a inhibitor)。定量荧光PCR(qRT-PCR)检测胃组织或细胞中MALAT1、miR-146a表达量;CCK-8法和克隆形成实验检测细胞增殖能力;Transwell法检测细胞侵袭和迁移能力;RNA pull down实验、双荧光素酶报告实验分析MALAT1和miR-146a的结合情况;Western blot检测磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase, PI3K)/蛋白激酶B(protein kinase B,Akt)通路蛋白及c-Myc、基质金属蛋白酶9(matrix metalloproteinase 9,MMP9)蛋白表达量。结果 转染MALAT1 siRNA可明显降低MNK-45细胞的MALAT1表达量,敲低MALAT1或过表达miR-146a可降低细胞活力、克隆能力、迁移和侵袭,增加miR-146a表达,降低PI3Kp85α、PI3Kp85β、c-Myc、MMP9蛋白表达量及p-Akt/Akt水平;MALAT1可结合并靶向下调miR-146a表达;低表达miR-146a可逆转敲低MALAT1对MNK-45细胞增殖、迁移和侵袭的抑制效应。结论 MALAT1可能作为ceRNA吸附并降解miR-146a,敲低MALAT1可上调miR-146a表达,并通过PI3K/Akt通路抑制GC细胞增殖、迁移和侵袭。

miR-29c-3p调控ERLIN2抑制肺腺癌发展的作用

目的:探讨miR-29c-3p在肺腺癌(lung adenocarcinoma,LUAD)发生发展中的作用。方法:利用公共数据库分析miR-29c-3p和ERLIN2在肺腺癌中的表达及其与临床病理参数的相关性。采用qRT-PCR检测miR-29c-3p在LUAD细胞系和正常支气管上皮细胞系中的表达,CCK8、细胞克隆形成、Transwell和伤口愈合实验评估miR-29c-3p在细胞增殖、迁移和侵袭中的作用,利用生物信息学工具预测miR-29c-3p下游靶基因,并通过双荧光素酶报告基因分析验证靶向关系。结果:miR-29c-3p在肺腺癌组织和细胞中低表达。miR-29c-3p低表达患者的预后较差,miR-29c-3p是肺腺癌患者的独立预后因素,并与淋巴结转移状态和临床分期密切相关。细胞实验表明,抑制miR-29c-3p可促进A549细胞的增殖、迁移和侵袭。生物信息学分析表明,ERLIN2是miR-29c-3p的靶基因,二者表达呈负相关。通过双荧光素酶报告基因测定验证了上述靶向关系。在UALCAN数据库中,ERLIN2在肺腺癌组织中高表达,并与患者年龄、性别、吸烟、肿瘤分期、淋巴结转移和TP53突变状态密切相关,ERLIN2高表达患者总生存率低于低表达患者。结论:miR-29c-3p通过靶向ERLIN2抑制肺腺癌细胞的增殖、迁移和侵袭,是肺腺癌患者的独立预后因素。

子宫颈浸润性复层产黏液的癌临床与病理分析(附12例)

目的:探讨子宫颈浸润性复层产黏液的癌(ISMC)临床病理学特征、诊断、鉴别诊断及治疗预后。方法:收集我院近3年诊断的子宫颈ISMC 12例,整理及分析其临床病理及随访资料并复习相关文献。结果:12例患者发病年龄为(51.1±7.4)岁,9例(75%)以阴道出血为主要症状,临床分期9例(75%)为Ib2期,2例(17%)为Ib3期,1例(8%)为Ⅲc2期;11例患者均在术后补充放、化疗,其中10例(91%)无复发,1例伴双肺多发转移;肿物最大径(32.4±5.5)mm;8例(67%)形成糜烂及结节状肿物,4例(33%)呈息肉样;镜下均可见典型的浸润性复层、实性、含黏液的癌细胞巢,巢周细胞呈栅栏状排列,除3例(25%)为纯的ISMC外,9例(75%)均合并其他类型的浸润性癌;12例(100%)查见宫颈上皮原位病变,包括子宫颈复层产黏液的上皮内病变、鳞状上皮内病变和原位腺癌;免疫表型ISMC表达腺上皮标记物,过碘酸酸酶/阿利新蓝染色(PAS/AB)染色阳性;10例行人乳头瘤病毒(HPV)检测,6例(50%)为18型,4例(33%)为16型。结论:ISMC具有独特的病理学特征,本文报道病例平均年龄偏大,临床分期偏早,虽然存在脉管癌栓,但随访至撰稿前仅1例发现转移,本文数据可为临床对该肿瘤的认识提供参考和补充。

lncRNA AL022344.4促进肺腺癌细胞侵袭及迁移的初步研究

目的:研究长链非编码RNA(long non-coding RNA,lncRNA)AL022344.4对人肺腺癌细胞H157和A549侵袭及迁移的影响。方法:选取TCGA_LUAD和GTEx_LUNG两个公共数据库中公开数据集对lncRNA AL022344.4表达数据进行生物信息学分析;qRT-PCR检测人正常支气管上皮细胞HBEC及肺腺癌细胞(H157、A549、H1299、H1975、CALU-3)中AL022344.4的相对表达量。慢病毒感染及质粒转染构建AL022344.4敲低H157细胞及过表达AL022344.4的A549细胞,qRT-PCR检测AL022344.4在两种细胞系中的表达;采用细胞划痕实验和Transwell实验检测AL022344.4敲低及过表达对肺腺癌细胞迁移、侵袭能力的影响;采用蛋白印迹法检测E-Cadherin、N-Cadherin、Vimentin、α-SMA、MMP9和ZEB1蛋白质表达水平。结果:生物信息学分析发现lncRNA AL022344.4在肺腺癌中较匹配的癌旁组织表达更高,qRT-PCR表明其在肺腺癌细胞中的表达亦高于正常支气管上皮细胞,差异有统计学意义(P<0.01);qRT-PCR表明AL022344.4敲低H157细胞系及过表达A549细胞系构建成功;细胞划痕和Transwell实验显示过表达AL022344.4促进A549细胞的迁移和侵袭,敲低AL022344.4抑制H157细胞迁移和侵袭;蛋白印迹法结果显示,过表达AL022344.4促进N-Cadherin、α-SMA、Vimentin、MMP9和ZEB1表达,降低E-Cadherin表达;敲低AL022344.4促进E-Cadherin表达,降低N-Cadherin、Vimentin、α-SMA、MMP9和ZEB1表达。结论:lncRNA AL022344.4通过促进ZEB1表达调控E-Cadherin、N-Cadherin、Vimentin和α-SMA,协同MMP9共同促进肺腺癌细胞的侵袭和迁移。

FUT7低甲基化和CT影像在肺浸润性腺癌中列线图预测模型的构建及评估

目的 基于FUT7低甲基化和CT影像构建列线图模型预测肺浸润性腺癌(invasive adenocarcinoma cancer, IAC)发生的风险。方法 回顾性分析114例经术后病理确诊为肺腺癌和腺体前驱病变肺结节患者的临床和CT影像资料,检测其血液中FUT7甲基化水平。根据病理结果分为浸润性腺癌组和侵袭前病变组,采用单因素分析和多因素Logistic回归构建列线图模型。效能评价使用受试者工作特征曲线(receiver operator characteristic curve, ROC)、校准曲线(calibration curve)、决策曲线分析法(decision curve analysis, DCA)。结果 浸润性腺癌组组较侵袭前病变组FUT7_CpG_1和FUT7_CpG_4甲基化水平更低,肺窗最长径更大,结节形状更不规则,混杂磨玻璃结节、毛刺征、分叶征和胸膜征占比更高(P<0.05)。其中FUT7_CpG_1、肺窗最长径、结节性质(实性、混杂磨玻璃)和毛刺征是IAC的独立影响因素(P<0.05)。列线图模型的ROC曲线下面积为0.934(95%CI:0.889~0.979,P<0.001),最大约登指数对应的临界值为0.476,此时敏感度为93.24%,特异度为80.00%,阳性预测值为89.61%,阴性预测值为86.48%。校准曲线显示列线图预测IAC的概率与实际概率高度一致。DCA曲线显示阈概率值为0.06~0.80时,列线图具有较高的临床净收益。结论 血液中FUT7_CpG_1和FUT7_CpG_4低甲基化是诊断IAC的新型潜在生物标志物。列线图模型在早期识别IAC具有较高的诊断效能和应用价值,可以为临床医生决策提供理论参考。

胸部CT影像学特征对肺腺癌亚实性结节脏层胸膜侵犯的预测价值

目的:探讨胸部CT影像学特征在肺腺癌亚实性结节(SSN)脏层胸膜侵犯(VPI)中的临床预测价值。方法:回顾性收集2016年5月-2021年12月在本院经手术切除和病理确诊为肺腺癌SSN的患者103例。男34例,女69例,年龄25~82岁,平均(58.5±10.2)岁。病理组织学诊断结果VPI阳性组19例(18.45%),VPI阴性组84例(81.55%)。记录患者的年龄、性别等临床资料。所有患者术前均行胸部CT检查。阅读CT影像学征象,包括位置、径线、密度、分叶征、毛刺征及胸膜凹陷征等。结节与胸膜关系(NPR)分为四种亚型:Ⅰ型,1条线相连;Ⅱ型,多条线相连;Ⅲ型,窄基底相贴;Ⅳ型,宽基底相贴。单因素分析比较VPI阳性组和阴性组在临床和CT影像学特征间的差异,将单因素分析差异有统计学意义的指标纳入多因素Logistic回归分析,通过受试者操作特征(ROC)曲线建立预测模型。结果:103例患者包括非实性结节49例(47.57%)和部分实性结节54例(52.43%)。VPI阳性组和阴性组的性别和年龄差异无统计学意义(P=0.883、0.151)。非实性结节VPI发生率为8.16%(4/49),低于部分实性结节27.78%(15/54),差异有统计学意义(P=0.01)。NPR四种亚型发生VPI的比例分别为Ⅰ型6.82%(3/44)、Ⅱ型15.00%(3/20)、Ⅲ型28.00%(7/25)和Ⅳ型42.86%(6/14),差异具有统计学意义(P=0.011)。结节密度和NPR分型是预测肺腺癌SSN的VPI状态的独立危险因素。ROC结果显示,结节密度诊断VPI的曲线下面积(AUC)为0.663,敏感度为78.9%,特异度为53.6%;NPR分型诊断VPI的AUC为0.726,敏感度为68.4%,特异度为69.0%;两者联合诊断VPI的AUC为0.804,敏感度为73.7%,特异度为70.2%。结论:肺腺癌亚实性结节的CT影像学特征有助于脏层胸膜侵犯的术前评估,结节密度和结节与胸膜关系分型是预测脏层胸膜侵犯的独立危险因素。