HSP90AA1 promotes lymphatic metastasis of hypopharyngeal squamous cell carcinoma by regulating epithelial-mesenchymal transition

Lymphatic metastasis(LM)emerges as an independent prognostic marker for hypopharyngeal squamous cell carcinoma(HSPSCC),chiefly contributing to treatment inefficacy.This study aimed to scrutinize the prognostic relevance of HSP90AA1 and its potential regulatory mechanism of concerning LM in HPSCC.Methods:In a preceding investigation,HSP90AA1,a differential gene,was discovered through transcriptome sequencing of HPSCC tissues,considering both the presence and absence of LM.Validation of HSP90AA1 expression was accomplished via qRT-PCR,western-blotting(WB),and immunohistochemistry(IHC),while its prognostic significance was assessed employing Kaplan–Meier survival analysis(KMSA),log-rank test(LR),and Cox’s regression analysis(CRA).Bioinformatics techniques facilitated the prediction and analysis of its plausible mechanisms in LM,further substantiated by in vitro and in vivo experiments utilizing FaDu cell lines.Results:HSP90AA1 is substantially upregulated in HPSCC with LM and is identified as an independent prognostic risk determinant.The down-regulation of HSP90AA1 can achieve inhibition of tumor cell proliferation,migration and invasion.Both in vivo experiments and Bioinformatics exploration hint at promoting LM by Epithelial-mesenchymal transition(EMT),regulated by HSP90AA1.Conclusions:HSP90AA1,by controlling EMT,can foster LM in HPSCC.This finding sets the foundation for delving into new therapeutic targets for HPSCC.

Extracellular vesicle-mediated heterogeneous communication between cancer and the lymphatic system facilitates lymphatic metastasis

Introduction The dissemination of cancer cells to organs initiates the formation of an aggressive cancer phenotype and is a predominant cause of cancer-associated death.For most epithelial cancers,lymphatic system metastasis has been characterized as the most common and earliest metastatic pathway,and the detection of metastasis in lymph nodes(LNs)often predicts poor survival among patients'.Although increasing attention is being paid to the clinical importance of LN metastasis,the underlying mechanisms have remained unclear in the past decade.Accumulating evidence suggests that the occurrence of LN metastasis is not stochastic but is a programming biological event regulated by the bidirectional crosstalk between metastasis-initiating cancer cells and the tumor microenvironment(TME)2.However,the regulators and patterns of cancer-TME communication in LN metastasis remain to be furtherexplored.

Roles of cancer-associated fibroblast functional heterogeneity in shaping the lymphatic metastatic landscape:new insights and therapeutic strategies

Lymph node (LN) metastasis is a process in which cancer cells travel from primary tumors to LNs via the lymphatic system,then proliferate and spread within the LNs. In most cancers,LN metastasis is a major mode of cancer dissemination,and a critical indicator of cancer progression and worsening prognosis1. The occurrence of LN metastasis indicates that the tumor has invaded the lymphatic system.

Study on the risk factors of lymphatic metastasis and the indications of less invasive operations in early gastric cancer

The principle of surgical treatment for gastric cancer is the radical resectioning although the suitable resecting range for different cases of gastric cancer is still being argued upon[1-9]. However, the diagnostic accuracy of early gastric cancer (EGC) without lymphatic metastasis has obviously improved with an improvement in the diagnostic technique and due to the accumulation of knowledge on the biological profiles of EG C[10-17]. The D2 lymph node excision was used as a regular operation to treat the EGC previously. But the concept for the EGC without lymphatic metastasis has gradually changed and the less invasive resections has been applied in some cases[18-20]. This study aimed at investigating the risk factors of lymphatic metastasis in EGC in order to find out the proofs for the suitable indications for less invasive operations such as endoscopic mucosal resectioning (EMR), laparoscopic and laparotomic resectioning.

Insulin-like growth factor-1 induces lymphangiogenesis and facilitates lymphatic metastasis in colorectal cancer

AIM:To investigate the expression of insulin-like growth factor-1(IGF-1)/insulin-like growth factor-1 receptor(IGF-1R)in colorectal cancer(CRC)tissues and to analyze their correlation with lymphangiogenesis and lymphatic metastasis.METHODS:Immunohistochemistry was used to evaluate IGF-1 and IGF-1R expression and lymphatic vessel density(LVD)in 40 CRC specimens.The correlation between IGF-1/IGF-1R and LVD was investigated.Effects of IGF-1 on migration and invasion of CRC cells were examined using transwell chamber assays.A LoVo cell xenograft model was established to further detect the role of IGF-1 in CRC lymphangiogenesis in vivo. RESULTS:Elevated IGF-1 and IGF-1R expression in CRC tissues was correlated with lymph node metastasis(r=0.715 and 0.569,respectively,P<0.05)and tumor TNM stage(r=0.731 and 0.609,P<0.05).A higher LVD was also found in CRC tissues and was correlated with lymphatic metastasis(r=0.405,P<0.05).A positive correlation was found between LVD and IGF-1R expression(r=0.437,P<0.05).Transwell assays revealed that IGF-1 increased the migration and invasion of CRC cells.In vivo mouse studies showed that IGF-1 also increased LVD in LoVo cell xenografts.CONCLUSION:IGF-1/IGF-1R signaling induces tumorassociated lymphangiogenesis and contributes to lymphatic metastasis of CRC.

Relationship between LYVE-1, VEGFR-3 and CD44 gene expressions and lymphatic metastasis in gastric cancer

AIM: To investigate the expression levels of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), vascular endothelial growth factor receptor-3 (VEGFR-3) and CD44 genes and the relationship between their lev- els and clinicopathological parameters in gastric cancer.METHODS: Tissue samples were obtained from 33 patients (8 females) with gastric cancer. mRNA levels of LYVE-1, VEGFR-3 and CD44 in normal and tumor tissues were quantitatively measured using real time polymerase chain reaction. The results were correlated with lymph node metastasis, histological type and differentiation of the tumor, T-stage, and presence of vascular, perineural and lymphatic invasions. The distribution of molecules in the tissue was evaluated using immunohistochemistry. RESULTS: LYVE-1, CD44 and VEGFR-3 gene expression levels were significantly higher in gastric cancer than in normal tissue. While there was no correlation between gene expressions and clinicopathologic fea- tures such as histologic type, differentiation and stage, gene expression levels were found to be increased in conjunction with positive lymph node/total lymph node ratio and the presence of perineural invasion. A significant correlation was also found between LYVE-1 and CD44 over-expressions and perineural invasion and lymph node positivity in gastric cancers. When the dis- tribution of LYVE-1 antibody-stained lymphatic vessels in tissue was evaluated, lymphatic vessels were located intra-tumorally in 13% and peri-tumorally in 27% of the patients. Moreover, lymph node metastases were also positive in all patients with LYVE-1-staining. CONCLUSION: LYVE-1, VEGFR-3 and CD44 all play an important role in lymphangiogenesis, invasion and metastasis. LYVE-1 is a perfectly reliable lymphatic vessel marker and useful for immunohistochemistry.

Lymphangiogenesis, Lymphatic Endothelial Cells and Lymphatic Metastasis in Head and Neck Cancer—A Review of Mechanisms

Lymphatic metastasis is a continuous and complicated process. The detailed mechanisms of lymphatic metastasis are still not very clear, despite considerable research efforts in recent years. Previously, it was commonly accepted that there were no lymphatic vessels in the primary tumor. However, recent studies have demonstrated that lymphatic vessels are detectable in certain types of cancer, and more and more evidence has shown that cancer cells invade into local lymph nodes mainly via peritumoral lymphatic vessels, Moreover, activated endothelial cells may also be important, having an influence on lymphatic metastasis of cancer cells. This article, based on recent research findings, provides an in-depth discussion of the relationship between lymphangiogenesis, tumor-derived lymphatic endothelial cells and lymphatic metastasis in head and neck cancer.

Identify lymphatic metastasis-associated genes in mouse hepatocarcinoma cell lines using gene chip

AIM: In order to obtain lymphogenous metastasisassociated genes, we compared the transcriptional profiles of mouse hepatocarcinoma cell lines Hca-F with highly lymphatic metastasis potential and Hca-P with low lymphatic metastasis potential.METHODS: Total RNA was isolated from Hca-F and Hca-P cells and synthesized into double-stranded cDNA. In vitro transcription double-stranded cDNA was labeled with biotin (i.e. biotin-labeled cRNA, used as the probe). The cRNA probes hybridized with Affymetrix GeneChip() MOE430A (containing 22 690 transcripts, including 14 500 known mouse genes and 4 371 ESTs) respectively and the signals were scanned by the GeneArray Scanner. The results were then analyzed by bioinformatics.RESULTS: Out of the 14 500 known genes investigated,110 (0.8%) were up regulated at least 23 fold. Among the total 4 371 ESTs, 17 ESTs (0.4%) (data were not presented) were up regulated at least 23 fold. According to the Gene Ontology and TreeView analysis, the 110genes were further classified into two groups: differential biological process profile and molecular function profile.CONCLUSION: Using high-throughput gene chip method,a large number of genes and their cellular functions about angiogenesis, cell adhesion, signal transduction, cell motility, transport, microtubule-based process, cytoskeleton organization and biogenesis, cell cycle, transcription,chaperone activity, motor activity, protein kinase activity,receptor binding and protein binding might be involved in the process of lymphatic metastasis and deserve to be used as potential candidates for further investigation.Cyclin D1, Fosl1, Hsp47, EGFR and AR, and Cav-1 are selected as the possible candidate genes of the metastatic phenotype, which need to be validated in later experiments.ESTs (data were not presented) might indicate novel genes associated with lymphatic metastasis. Validating the function of these genes is helpful to identify the key or candidate gene/pathway responsible for lymphatic metastasis, which might be used as the diagnostic markers and the therapeutic targets for lymphatic metastasis.

Matrix metalloproteinase-9-1562C>T polymorphism may increase the risk of lymphatic metastasis of colorectal cancer

AIM. To explore the role of the matrix metalloproteinase-9 （MMP-9） polymorphism in colorectal cancer （CRC） in a northeast Chinese population.METHODS： Genotyping of MNP-9-1562C〉T and 279R〉Q polymorphisms was carried out on blood samples from 137 colorectal cancer patients and 199 controls using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Multivariate logistic regression models were used to calculate adjusted odds ratios （OR） and 95% confidence intervals （95% CI）.RESULTS： The distribution of IVllVlP-9 -2562C〉T and 279 R〉Q genotype was not significantly associated with the risk of CRC. However, the risk of Ilymph node metastasis of CRC was increased in patients with the -1562T allele （OR = 2.601; 95% CI = 1.160-5.835; P = 0.022）. The frequency of MMP-9 279RR ＋ RQ genotype was higher than the QQ genotype among CRC patients younger than sixty years old （OR = 0.102, 95% CI = 0.013-0.812; P = 0.012）.CONCLUSION： Our results indicated that the MMP-9- 1562C〉T polymorphism affects lymph node metastasis of CRC. In addition, the MMP-9 279R allele may lead to a younger age of onset of colorectal cancer.

Recent advances in lymphatic targeted drug delivery system for tumor metastasis

The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.

KAI1 inhibits lymphangiogenesis and lymphatic metastasis of pancreatic cancer in vivo

BACKGROUND: Several studies have shown that KAI1 inhibits tumor metastasis, but its mechanism is not clear. The present study aimed to determine the role of KAI1 in lymphatic metastasis, specifically in pancreatic cancer. METHODS: The KAI1 gene was transfected into the pancreatic cancer cell line MIA PaCa-2 and PANC-1 by using liposomes and selected by G418, and the protein was measured by Western blotting. After successful infection, the cell growth curve was studied by MTT, vascular endothelial growth factor C(VEGF-C) secretion by pancreatic cancer cell were measured by ELISA. The KAI1 and pCMV transfected MIA PaCa-2 cells were renamed as MIA PaCa-2-K and MIA PaCa-2-p. These two kinds of cells were injected into the subcuticular layer of nude mice; both tumor growth and metastasis through the lymphatic nodes were assessed. Lymphangiogenesis in tumors was measured by immunohistochemistry. RESULTS: The VEGF-C secretion was significantly reduced in MIA PaCa-2 cells compared with PANC-1 cells after being transfected with the KAI1 gene. The growth rate of subcutaneous tumors was similar after the injection of MIA PaCa-2-K, MIA PaCa-2, and MIA PaCa-2-p. MIA PaCa-2-K tumors showed slower lymphangiogenesis and lymph node metastasis compared with MIA PaCa-2 and MIA PaCa-2-p tumors. CONCLUSION: The overexpression of KAI1 inhibits the lymphangiogenesis and lymph node metastasis of MIA PaCa-2 pancreatic tumors.

Risk factors of lymphatic metastasis complement poor radiological detection in gallbladder cancer

AIM: To explore risk factors of lymphatic metastasis (LM) in gallbladder cancer, and their potential to complement unsatisfactory radiological detection.

Genetic Fingerprint Concerned with Lymphatic Metastasis of Human Lung Squamous Cancer

背景与目的筛选肺鳞癌患者淋巴转移差异表达基因群。方法原发癌组织及区域淋巴结取自10例接受完全性肺癌切除手术的肺鳞癌患者。根据组织来源将标本分为三组:不伴淋巴转移的肺鳞癌组织(TxN-,n=5)、伴有淋巴转移的肺鳞癌组织(TxN+,n=5)及相应转移淋巴结中的肺鳞癌细胞(N+,n=5)。对各组进行激光显微切割以获得纯净癌细胞,T7RNA线性扩增获取足够量的RNA,实验通道和参照通道分别标记以后与含6000个已知人类基因或表达序列标签的cDNA基因芯片杂交,扫描荧光信号以后进行数据分析。结果共有37个基因可将TxN+组与TxN-组区分开,其中在TxN+组高表达的基因有8个,主要涉及蛋白合成、信号传导、伴侣蛋白和酶等。有29个基因在TxN-组高表达,这些基因主要编码细胞周期调节子、转导子、信号传导蛋白以及细胞凋亡调节蛋白。比较N+组与TxN+组却没有发现具有显著性的差异表达基因。结论肺鳞癌的淋巴转移表型的获得可能是早期事件。这些差异基因的发现有助于阐明肺鳞癌淋巴转移的分子机制和寻找新的治疗靶点。

Axl glycosylation mediates tumor cell proliferation, invasion and lymphatic metastasis in murine hepatocellular carcinoma

AIM: To investigate the effects of Axl deglycosylation on tumor lymphatic metastases in mouse hepatocellular carcinoma cell lines. METHODS: Western blotting was used to analyze the expression profile of Axl glycoprotein in mouse hepa-tocellular carcinoma cell line Hca-F treated with tunicamycin and PNGase F 3-(4,5)-dimethylthiazol(-zyl)-3,5- diphenyltetrazolium bromide (MTT) assay, extracellular matrix (ECM) invasion assay (in vitro ) and tumor metastasis assay (in vivo ) were utilized to evaluate the effect of Axl deglycosylation on the Hca-F cell proliferation, invasion and lymphatic metastasis. RESULTS: Tunicamycin and PNGase F treatment markedly inhibited Axl glycoprotein synthesis and expression, proliferation, invasion, and lymphatic metastasis both in vitro and in vivo . In the MTT assay, proliferation was apparent in untreated Hca-F cells compared with treated Hca-F cells. In the ECM invasion assay (in vitro ), treated cells passed through the ECMatrix gel in significantly smaller numbers than untreated cells (tunicamycin 5 μg/mL: 68 ± 8 vs 80 ± 9, P=0.0222; 10 μg/mL: 50 ± 6vs 80 ± 9,P=0.0003; 20 μg/mL: 41 ± 4 vs 80 ± 9, P=0.0001); (PNGase F 8 h: 66 ± 7 vs 82 ± 8, P=0.0098; 16 h: 49 ± 4 vs 82 ± 8, P=0.0001; 24 h: 34 ± 3 vs 82 ± 8, P=0.0001). In the tumor metastasis assay (in vivo ), average lymph node weights of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 0.84 ± 0.21 g vs 0.72 ± 0.19 g, P=0.3237; 10 μg/mL: 0.84 ± 0.21 g vs 0.54 ± 0.11 g, P=0.0113; 20 μg/mL: 0.84 ± 0.21 g vs 0.42 ± 0.06 g, P=0.0008); (PNGase F 8 h: 0.79 ± 0.15 g vs 0.63 ± 0.13 g, P=0.0766; 16 h: 0.79 ± 0.15 g vs 0.49 ± 0.10 g, P=0.0022; 24 h: 0.79 ± 0.15 g vs 0.39 ± 0.05 g, P=0.0001). Also, average lymph node volumes of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 815 ± 61 mm 3 vs 680 ± 59 mm 3 , P=0.0613; 10 μg/mL: 815 ± 61 mm 3 vs 580 ± 29 mm 3 , P=0.0001; 20 μg/mL: 815 ± 61 mm 3 vs 395 ± 12 mm 3 , P=0.0001); (PNGase F 8 h: 670 ± 56 mm 3 vs 581 ± 48 mm 3 , P=0.0532; 16 h: 670 ± 56 mm 3 vs 412 ± 22 mm 3 , P=0.0001; 24 h: 670 ± 56 mm 3 vs 323 ± 11 mm 3 , P=0.0001). CONCLUSION: Alteration of Axl glycosylation can at-tenuate neoplastic lymphatic metastasis. Axl N-glycans may be a universal target for chemotherapy.

Targeting Annexin A7 in Hepatocarcinoma Lymphatic Metastasis

Background and objective The rst aim was to measure the expressions of Annexin A7 (Anxa7) at mRNA level and protein level in two mice hepatocarcinoma ascites syngeneic cell

COMPARATIVE ANALYSIS OF LYMPHATIC METASTASIS——ASSOCIATED GENES IN MOUSE HEPATOCELLULAR CARCINOMA CELL LINES WITH DIFFERENT METASTATIC POTENTIAL

Objective： To investigate the neoplasm lymphatic metastasis-associated genes and its molecular mechanisms. Methods： 22690 mouse genome cDNA microarrays （including 14500 known genes and 4371 ESTs） were used to compare and analyze the gene expression profiles of mouse hepatocellular carcinoma cell lines Hca-F （highly lymphatic metastasis potential） and Hca-P （low potential）. Results： 901 genes and 129 ESTs were up-regulated at least 2-fold in Hca-F cell. 33 genes showing significant alterations in expression were presented, including endoglin （EDG）, MCAM, Cdc42ep5, F2r, D7Ertd458e, Serpin hl （HSP47）, AXL, Areg and so on. These genes have functions of angiogenesis, cell adhesion, signal transduction, cell motility, chaperone activity, protein kinase activity and receptor binding. Conclusion： cDNA microarray combined with lymphatic metastasis models might contribute new methods and clues to the neoplasm lymphatic metastasis research. Some overexpressed genes might provide novel clues to the molecular mechanisms of neoplasm lymphatic metastasis.

Papillary thyroid microcarcinoma with contralateral lymphatic skip metastasis and breast cancer: A case report

BACKGROUND The recognized pattern of cervical lymph node metastasis(CLNM)of papillary thyroid carcinoma involves a stepwise route.Contralateral lymph node skip metastasis is very rare.In addition,the patient in our case report also suffered from a breast carcinoma accompanied by left supraclavicular lymphadenopathy,which made it difficult to distinguish the origin of the CLNM.Based on this case,we recommended that more detailed physical and imaging examinations are needed for patients with uncommon cervical lymphatic metastasis of primary cancer.CASE SUMMARY A 53-year-old women was admitted to the hospital for a neck mass in the left cervical region that had existed for 2 mo.The neck mass was suspected to be an enlarged lateral LN originating from papillary thyroid microcarcinoma of the contralateral thyroid lobe,according to ultrasound and ultrasound-guided fine needle aspiration biopsy.The patient underwent total thyroidectomy and radical cervical LN dissection.Postoperative pathology confirmed the diagnosis of papillary thyroid microcarcinoma with contralateral lymphatic skip metastasis.Unfortunately,a breast cancer was discovered 4 mo later,which was accompanied by ipsilateral supraclavicular LN metastasis.She accepted neoadjuvant chemotherapy and subsequent left modified radical mastectomy for treatment.The patient is currently receiving postoperative radiotherapy,and no local recurrence was observed in the 6-mo follow-up after surgery.CONCLUSIONWe present a rare case of papillary thyroid microcarcinoma with contralateral lymphatic skipmetastasis and breast cancer with supraclavicular lymphatic metastasis.

Pattern of Lymphatic Metastasis and Influencing Factors in Thoracic Esophageal Carcinoma

OBJECTIVE To explore the regular patterns of lymphatic metastasis in thoracic esophageal carcinoma （TEC） and the factors influencing these patterns. METHODS Data of 229 TEC patients who underwent radical esophagectomy and thoracoabdominal 2-field lymphadenectomy were reviewed. Within this patient population, a total of 2458 lymph nodes were dissected during surgery. The distribution of the nodular metastasis rates （NMR） in various diseased regions in the esophageal carcinoma （EC） patients as well as factors influencing metastases such as the depth of tumor infiltration, tumor size, tumor morphology, and degree of tumor differentiation were analyzed. RESULTS i） Lymphatic metastasis （LM） occurred in 102 EC cases, and the lymphatic metastasis rate （LMR） was 44.5% （102/229）. The NMR was 9.5% （258/2458）. ii） The NMRs were 19.0%, 6.7%, 9.8% and 12.2% in the superior, middle and inferior mediastinum, and abdominal cavity, respectively, in patients with EC in the superior thoracic segment; 26.1%, 7.4%, 11.8% and 11.9% in the same sites of the mediastinum, respectively, in those with middle thoracic-segment EC; and 0%, 1.6%, 5.3%, and 10.0%, respectively, in the same sites in those with inferior thoracic EC. iii） The LMRs of the EC patients in stage-T1, T2, T3 and T4 were 28.6%, 43.8%, 47.6% and 31.3%, respectively, and the NMRs of the patients were 7.9%, 10.8%, 10.7% and 10.8%, respectively. There were no significant differences between the LMR and the NMR of the EC patients in stage T1 to T4 （X^2 = 2.733, P = 0.435 and X2 = 0.686, P = 0.876）. iv） The LMR of the patients with the length of tumor 〈 3 cm, 〉 3 cm and 〈 5 cm, and 〉 5 cm were 45.2%, 43.4% and 46.2%, respectively, and the NMR according to the same range of the tumor size above were 9.1%, 11.6% and 11.7%, respectively. There were no significant differences between the groups （X2 --- 0.094, P = 0.954 and X2 = 3.933, P = 0.140）. v） The NMRs of the medullary, ulcerative, fungoid and sclerotic-type EC were 14.0%, 9.6%, 4.3% and 18.3%, respectively （X^2 = 19.292, P = 0.000）, among which the NMR of the fungoid-type EC was the lowest. The LMRs were 42.5% and 75.0%, respectively in the cases with squamous cell carcinoma （SqCC） and poorly differentiated SqCC （X^2 = 4.852, P = 0.028）, and the NMRs were 9.5% and 18.6% correspondingly in the 2 groups （X^2 = 11.323, P = 0.001）. LM was commonly seen in the cases with poorly differentiated tumors. CONCLUSION Lymph node metastases of TEC spreads widely and can involve many regions. Metastasis can even be found in early stages of EC. Morphologic type and the degree of tumor differentiation are the main factors affecting the LM.

Investigation of the relationship between DNA-dependent protein kinase and lymphatic metastasis in colorectal cancer

Objective: To investigate DNA-dependent protein kinase (DNA-PK) expression,and its relationship with lymphat-ic metastasis in colorectal cancer. Methods: Tumor tissues from 60 patients,divided into two groups according to lymphatic metastasis,were immunohistochemically stained to detect the DNA-PK expression including Ku70,Ku80 and PKcs proteins. Results: Positivity of both Ku70 and Ku80 in colorectal cancer was negatively correlated with lymphatic metastasis with an r value of -0.57 and -0.38,respectively. Similar correlation was found between Ku expression,especially Ku70,and long-term survival. PKcs,however,displayed no significant correlation. Statistical analysis failed to detect any correlation between DNA-PK expression,and clinical characteristics,such as age,sex,tumor location,tumor thickness and distant metastasis (P>0.05). Conclusion: DNA-PK expression,especially Ku70 expression,is negatively correlated with lymphatic metastasis,and the survival of patients with colorectal cancer. Ku70 expression may be a potential indicator for the preoperative evaluation,and prognosis in colorectal cancer.

Diagnostic value of conventional endoscopic ultrasound for lymph node metastasis in upper gastrointestinal neoplasia:A metaanalysis

BACKGROUND Upper gastrointestinal neoplasia mainly includes esophageal cancer and gastric cancer,both of which have high morbidity and mortality.Lymph node metastasis(LNM),as the most common metastasis mode of both diseases,is an important factor affecting tumor stage,treatment strategy and clinical prognosis.As a new fusion technology,endoscopic ultrasound(EUS)is becoming increasingly used in the diagnosis and treatment of digestive system diseases,but its use in detecting LNM in clinical practice remains limited.AIM To evaluate the diagnostic value of conventional EUS for LNM in upper gastrointestinal neoplasia.METHODS Using the search mode of“MeSH+Entry Terms”and according to the predetermined inclusion and exclusion criteria,we conducted a comprehensive search and screening of the PubMed,EMBASE and Cochrane Library databases from January 1,2000 to October 1,2022.Study data were extracted according to the predetermined data extraction form.The quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool,and the results of the quality assessment were presented using Review Manager 5.3.5 software.Finally,Stata14.0 software was used for a series of statistical analyses.RESULTS A total of 22 studies were included in our study,including 2986 patients.The pooled sensitivity,specificity,positive likelihood ratio,negative likelihood ratio,diagnostic score and diagnostic odds ratio of conventional EUS in the diagnosis of upper gastrointestinal neoplasia LNM were 0.62[95%confidence interval(CI):0.50-0.73],0.80(95%CI:0.73-0.86),3.15(95%CI:2.46-4.03),0.47(95%CI:0.36-0.61),1.90(95%CI:1.51-2.29)and 6.67(95%CI:4.52-9.84),respectively.The area under the summary receiver operating characteristic curve was 0.80(95%CI:0.76-0.83).Sensitivity analysis indicated that the results of the meta-analysis were stable.There was considerable heterogeneity among the included studies,and the threshold effect was an important source of heterogeneity.Univariable meta-regression and subgroup analysis showed that tumor type,sample size and EUS diagnostic criteria were significant sources of heterogeneity in specificity(P<0.05).No significant publication bias was found.CONCLUSION Conventional EUS has certain clinical value and can assist in the detection of LNM in upper gastrointestinal neoplasia,but it cannot be used as a confirmatory or exclusionary test.