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

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

Expression of nm23 gene in hepatocellular carcinoma tissue and its relation with metastasis

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Aberrant methylation of the 3q25 tumor suppressor gene PTX3 in human esophageal squamous cell carcinoma

AIM:To identify the novel methylation-silenced gene pentraxin 3(PTX3) in esophageal squamous cell carcinoma(ESCC).METHODS:PTX3 mRNA expression was examined in six human ESCC cell lines,one human immortalized normal esophageal epithelial cell line,primary ESCC tumor tissue,and paired adjacent nontumor tissue using reverse transcription polymerase chain reaction(RTPCR).Semi-quantitative immunohistochemistry was used to examine cellular localisation and protein levels.Methylation specific PCR and bisulphite genomic sequencing were employed to investigate the methylation of the candidate gene.RESULTS:In the majority of ESCC cell lines,we found that PTX3 expression was down-regulated due to gene promoter hypermethylation,which was further confirmed by bisulphite genomic sequencing.Demethylation treatment with 5-aza-2'-deoxycytidine restored PTX3 mRNA expression in ESCC cell lines.Methylation was more common in tumor tissues(85%) than in adjacent nontumor tissues(25%)(P < 0.01).CONCLUSION:PTX3 is down-regulated through promoter hypermethylation in ESCC,and could potentially serve as a biomarker of ESCC.

Promoter methylation of tumor suppressor genes in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recently,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis prediction.This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.

Effects of body-resistance strengthening and tumor-suppressing granules on immune adhesion function of red blood cells and expression of metastasis protein CD44 in tumor cells of patients with esophageal carcinoma

AIM： To investigate the effects of Fuzheng Yiliu granules （body-resistance strengthening and tumor-suppressing granules） in patients with esophageal carcinoma. METHODS： We compared the immune adherent properties of red blood cells （RBCs）, the expression of metastasis protein CD44, and the metastasis inhibition factor nm23, in esophageal carcinoma tumor cells of patients before and after radiotherapy in the presence and absence of orally administered Fuzheng Yiliu granules. Sixty-three hospitalized patients with esophageal carcinoma were treated with standard radiotherapy and randomly divided into treatment group （n = 30） treated with both radiotherapy and Fuzheng Yiliu granules and control group （n = 33） given radiotherapy only. Blood samples and tumor tissue were obtained before and after 21 d of treatment. The rosette rates for complement receptor type 3b （C3bRR） and immune complex receptor （ICRR） on RBCs were measured by erythrocyte immunological methods. Expression of CD44 and rim23 in tumor tissue sections was determined by immunohistochemical staining with monoclonal antibodies CD44v6 ad nm23H-1, respectively. RESULTS： The positivity of RBC-C3bRR before and after 21 d of treatment increased from 7.78% ± 1.59% to 10.03% ± 2.01% in the double treatment group, while it changed only slightly from 7.18% ± 1.29% to 7.46% ± 1.12% in the radiotherapy group. The positive rate for RBC-ICRR decreased from 37.68% ± 2.51% to 22.55% ± 1.65% after the double treatment, and from 37.28% ± 2.41% to 24.69% ± 1.91% in radiotherapy group at the same time points. The difference in erythrocyte immune adherent function between the two groups was significant （P 〈 0.01, t-test）. The CD44^± - cases were reduced from 21 （70.00%） to 12 （40.00%） after treatment with Fuzheng Yiliu granules, whereas the CD44^± -cases （69.70%） in the radiotherapy group remained unchanged. The difference between the treatment （40.00%） and control （69.70%） groups was significant （P 〈 0.05）. Although the nm23^± -cases were increased from 4 （13.33%） to 6 （20.00%） in the double treatment group and from 6 （18.18%） to 7 （21.21%） in the radiotherapy group, the difference was not significant （P 〉 0.05）. CONCLUSION： Fuzheng Yiliu granules enhance the immune adhesion function of RBCs and reduce the number of CD44^± -cells in esophageal carcinoma patients, suggesting a potential role of these Chinese herbals in suppression of invasion and metastasis of malignant cells. However, this anti-metastatic effect has yet to be validated in vivo.

Expression Profile of Metastasis-associated Genes in Esophageal Squamous Cell Carcinoma

The differentially expressed genes between esophageal squamous cell carcinoma （ESCC） with or without lymphatic metastasis were investigated by gene chip, and the lymphatic metastasisassociated genes were screened out. Expression array was used to detect the mRNA from both the primary carcinoma and the corresponding esophageal epithelium in 15 cases of human ESCC. The lymphatic metastasis-associated genes were screened by bioinformatics between ESCC with or without lymphatic metastasis. The results showed that 43 （4. 85 %） genes significantly differed between the ESCC with and without lymphatic metastasis （P〈0.05）, of which 18（2.03 %）were upregulated and 25 （2.82 %） down-regulated. The up-regulated genes were involved in cell adhesion molecules and cell membrane receptors and the down-regulated genes were mostly cell cycle regulators and intracellular signaling molecules. It was suggested that lymphatic metastasis-associated genes were screened by gene chip, which was helpful to understand the molecular mechanism of ESCC lymphatic metastasis and lymphatic metastasis-associated genes might be used as diagnostic markers and therapeutic targets for lymphatic metastasis.

THE ASSOCIATION OF THE EXPRESSION OF MTA1, NM23H1 WITH THE INVASION, METASTASIS OF OVARIAN CARCINOMA

Objective. To understanding the molecular mechanisms in invasion andmetastasis of the ovarian carcinoma, we investigate a novel candidate metastasis―associated gene (MTA1) and nm23Hl mRNA expression and mutation in ovarian carcinoma. Methods. Twenty primary ovariancarcinoma specimens, 20 corresponding lymph nodes and 8 normal ovarian was examined for mRNAexpression and mutation of MTA1 and nm23Hl genes by reverse-transcription ploymerase chain reaction(RT―PCR) and RT―PCR―SSCP analysis. The level of the expression was determined by the relativeoptic desity (ROD) of the PCR products. Results. The frequency of MAT1 overexpression was 100% (7/7)in primary ovarian carcinoma with metastasis but only 38.5% (5/13) in those without metastasis(P=0.0103). Overexpression of MAT1 was observed in 87.5% (6/7) of lymph nodes with metastasis butonly 23% (3/13). of lymph nodes without metastasis (P=0.0118). In contrast with MAT1, low expressionof nm23H1 mRNA was seen in 7 of 7 o-varian carcinoma with metastasis but only in 4 of 13(30%) ofthose without metastassis (P=0.0043). Low nm23H1 expression was also seen in 7 of 7 lymph nodes withmetastasis but only in 5 of 13 (38.5%) nonmetastatic lymph nodes (P=0.0102). The ROD ratio of MAT1to nm23Hl increased with the development of metastasis. No mutation of MAT1 and nm23H1 genes wasfound by SSCP analysis. Conclusion. The mRNA expression of MTA1 and nm23H1 is positively andnegatively correlated with lymph node metastasis, respectively. Expression abnormalities but notmutation of the two genes are frequent events related to lymph node metastasis of ovarian cancer.

Study on RIZ1 gene promoter methylation status in human esophageal squamous cell carcinoma

AIM： To investigate the promoter region methylation status of retinoblastoma protein-interacting zinc finger gene 1 （RIZ1） in the human esophageal squamous cell carcinoma （ESCC） cell lines and tissues and verify the relationship between methylation of RIZ1 and oncogen- esis, tumor progression and metastasis etc of ESCC. METHODS： Methylation-specific polymerase chain reac- tion （MSP） was used to investigate the promoter region methylation status of RIZ1 in 6 ESCC cell lines. One cell line where RIZ1 promoter region methylation was de- tected was selected for the next study, where the cell line was treated with 5-aza-CdR. Real-time polymerase chain reaction was used to investigate its influence on the transcription of RIZ1. Experiments using frozenpathological specimens from 47 ESCC patients were performed using the same MSP methodology. RESULTS： Promoter methylation of RIZ1 gene was detected in TEl3, CaEs17 and EC109 cell lines and the cell line TEl3 was chosen for further study. The expression of RIZl mRNA in TE-13 was up-regulated after treatment with 5-aza-CdR. The rate of methyla- tion in carcinomas tissues was significantly higher than those in matched neighboring normal and distal ending normal tissue, and the deviation of data was statisti- cally significant （2,2 = 24.136, P 〈 0.01）. Analysis of the gender, age familial history, tumour deviation, tumour saturation, lymph gland displacement and clinical stag- ing of 47 samples from ESCC patients showed that the fluctuation of data was not statistically significant. CONCLUSION： Promoter methylation may play an im- portant role in the epigenetic silencing of RIZ1 gene expression in human ESCC. RIZ1 is considered to be a potential tumor suppressor gene and may be a biologi- cal parameter for testing early stage human ESCC.

Epigenetic inactivation of secreted frizzled-related protein 2 in esophageal squamous cell carcinoma

AIM： To investigate the expression and methylation status of the secreted frizzled-related protein 2 （SFRP2） in esophageal squamous cell carcinoma （ESCC） and ex- plore its role in ESCC carcinogenesis.METHODS： Seven ESCC cell lines （KYSE 30, KYSE150, KYSE410, KYSE510, EC109, EC9706 and TE-1） and one immortalized human esophageal epithelial cell line （Het- 1A）, 20 ESCC tissue samples and 20 paired adjacent non-tumor esophageal epithelial tissues were analyzed in this study. Reverse-transcription polymerase chain reaction （RT-PCR） was employed to investigate the expression of SFRP2 in cell lines, primary ESCC tumor tissue, and paired adjacent normal tissue. Methylation status was evaluated by methylation-specific PCR and bisulfite sequencing. The correlation between expres- sion and promoter methylation of the SFRP2 gene was confirmed with treatment of 5-aza-2＇-deoxycytidine. To assess the potential role of SFRP2 in ESCC, we es-tablished stable SFRP2-transfected cells and examined them with regard to cell proliferation, colony formation, apoptosis and cell cycle in vivo and in vitro.RESULTS： SFRP2 mRNA was expressed in the im- mortalized normal esophageal epithelial cell line but not in seven ESCC cell lines. By methylation-specific PCR, complete methylation was detected in three cell lines with silenced SFRP2 expression, and extensive methylation was observed in the other four ESCC cell lines. 5-aza-2＇-deoxycytidine could restore the expres- sion of SFRP2 mRNA in the three ESCC cell lines lack- ing SFRP2 expression. SFRP2 mRNA expression was obviously lower in primary ESCC tissue than in adjacent normal tissue （0.939 ± 0.398 vs 1.51 ± 0.399, P 〈 0.01）. SFRP2 methylation was higher in tumor tissue than in paired normal tissue （95% vs 65%, P 〈 0.05）. The DNA methylation status of the SFRP2 correlated inversely with the SFRP2 expression. To assess the potential role of SFRP2 in ESCC, we established stable SFRP2 transfectants and control counterparts by in- troducing pcDNA3.1/v5 hisA -SFRP2 or pcDNA3.1/v5 hisA -empty vector into KYSE30 cells lacking SFRP2 expression. After transfection, the forced-expression of SFRP2 was confirmed by the RT-PCR. In comparison with the control groups, stably-expressed SFRP2 in KYSE 30 cells significantly reduced colony formation in vitro （47.17% 4± 15.61% vs 17% ：1： 3.6%, P = 0.031） and tumor growth in nude mice （917.86：1：249.35 mm3 vs 337.23 ± 124.43 mm3, P 〈 0.05）. Using flow cytom- etry analysis, we found a significantly higher number of early apoptotic cells in SFRP2-transfected cells than in the control cells （P = 0.025）. The mean cell number in the S and G2-M phases of the cell cycle was also significantly lower in SFRP2-transfected KYSE30 cells compared with mock transfected counterparts. CONCLUSION： Silencing of SFRP2 expression through promoter hypermethylation may be a factor in ESCC carcinogenesis through loss of its tumor-suppressive activity.

RELATIONSHIP BETWEEN THE MUTATION OF P53 GENE AND INFILTRATION，METASTASIS AND PROGNOSIS OF GASTRIC CARCINOMA

gastric carcinomas were examined immunohistochemically with McAb to p53 protein in order to investigate the relationship between the expression of p53 protein and histological differentiation of gastric carcinoma, and to approach the mechanism of infiltration and metastasis of gastric carcinoma. The results showed that nuclear expression of p53 protein was significantly related to tumor size, depth of invasion, lymph node and liver metastases; but not related to histological differentiation. It is suggested that the accumulation of p53 protein was increased with the progression of gastric carcinoma, and therefore the cancer clone with p53 gene mutation may play an important role in the development of tumor invasion and metastasis.

EXPRESSION OF NM23-H1 GENE PRODUCT IN NASOPHARYNGEAL CARCINOMA AND ITS CLINICAL SIGNIFICANCE

Objective: The nm23 gene is one of the tumor metastatic suppressor genes. The expression of nm23H1 has been reported to be inversely associated with metastatic potentiality in a number of human carcinomas, including breast, colorectal, gastric, hepatocellular and gallbladder carcinomas. In this study, the immunohistochemical staining of nm23H1 protein in human nasopharyngeal carcinoma (NPC) was examined, and the relationship between nm23H1 and both metastasis and prognosis of patients with NPC was also investigated. Methods: Routine LSAB immunohistochemistry with the nm23H1 monoclonal murine antibody was employed to study the expression of nm23H1 protein in 95 paraffinembedded specimens of NPC treated at our hospital. The clinical pathologic data and results of followup were also retrieved. Comparisons between patients with and without expression of nm23H1 protein with respect to metastasis, locoregional recurrence and survival were performed using Log rank test. Multivariate prognostic analyses were performed by using Cox's regression model. Results: Nm23H1 negative expressive tumors were associated with a higher incidence of lymphnode metastasis (86.7%) than those of nm23H1 positive (48.6%, P<0.01). Nm23H1 negative expressive tumors were associated with a high incidence of recurrence and distant metastasis after radiotherapy (P<0.05). A significant association was found between expression of nm23H1 and prognosis (P<0.01). The expression of nm23H1 indicated favorable prognosis. Conclusion: It was suggested that nm23 H1 negative expression was significantly associated with lymphnode metastasis, recurrence and distant metastasis. Nm23H1 may have value for predicting the prognosis of NPC.

Tiaml gene expression and its significance in colorectal carcinoma

AIM: To explore the expression of Tiam1 gene in colorectal carcinoma and its correlation with tumor metastasis. METHODS: Expressions of Tiaml gene in 8 colorectal carcinoma cell lines were detected by reverse transcriptase-polymerase chain reaction. In vitro invasiveness was determined by means of Matrigel invasion assay. The correlation of Tiaml expression with the invasive ability was also analyzed. RESULTS: Tiaml gene was highly expressed in LoVo and SW620, which were established from metastatic colorectal carcinomas in comparison with LS174T, SW480, HCT116, LST, HRT-18 and Hee8693, which were established from primary colorectal carcinomas. In vitro cell invasivion demonstrated that LoVo and SW620 had a higher invasive ability than LS174T, SW480, HCT116, LST, HRT-18 and Hee8693. The expression of Tiaml gene was highly related to the metastatic potential of colorectal carcinoma cells. CONCLUSION: Tiaml gene may play an important role in invasion and metastasis of colorectal carcinoma and is a metastasis-related gene.

Expression of human chorionic gonadotropin, CD44v6 and CD44v4/5 in esophageal squamous cell carcinoma

AIM： To study the relationship between the expression of human chorionic gonadotropin （HCG）, CD44v6, CD44v4/5 and the infiltration, metastasis of esophageal squamous cell carcinoma. METHODS： By labeled streptavidin-biotin technique, the expressions of HCG, CD44v6, and CD44v4/5 in 42 patients with esophageal squamous cell carcinoma were examined. RESULTS： The positive rate of HCG expression in patients with lymph node metastasis was 85.71% （18/21）, higher than that （57.14%, 12/21） in those without lymph node metastasis （P〈0.05）. The positive rate of CD44v6 expression was 71.43% （15/21） in lymph node metastasis group, and 38.09% （8/21） in nonmetastasis group; there was a significant difference between the two groups （P〈0.05）. The positive rate of CD44v4/5 expression was 76.19% （16/21） in lymph node metastasis group, and 42.86% （9/21） in non-metastasis group; there was also a significant difference between them （P〈0.05）. From grade Ⅰ to grade Ⅲ in differentiation, the positive rate of HCG expression was 84.62% （11/13）, 70.59% （12/17） and 58.33% （7/12）, respectively, there was no significant difference among them （P〉0.05）. The positive rate of CD44v6 expression in grades Ⅰ-Ⅲ of cancer tissues was 76.92% （10/13）, 52.94% （9/17）, and 33.33% （4/12） respectively; there was no significant difference among them. The positive rate of CD44v4/5 expression in grades Ⅰ-Ⅲ of cancer tissues was 69.23% （9/13）, 64.71% （11/17）, and 41.67% （5/12） respectively; there was no significant difference among the three groups. There was no correlation between the positive rates of HCG and CD44v6, CD44v4/5 expression. Cancer cells in carcinomatous emboli and those infiltrating into vascular wall strongly expressed HCG, CD44v6, and CD44v4/5. CONCLUSION： Expression of HCG, CD44v6, and CD44v4/5 in esophageal squamous cell carcinoma is related to its infiltration and metastasis. HCG, CD44v6, and CD44v4/5 have different effects on the infiltration and metastasis of esophageal squamous cell carcinoma.

Clinical significance of serum expression of GROβ in esophageal squamous cell carcinoma

AIM:To determine the association between serum levels of growth-related gene product β(GROβ) and clinical parameters in esophageal squamous cell carcinoma(ESCC).METHODS:Using enzyme-linked immunosorbent assay,serum GROβ levels were measured in ESCC patients(n = 72) and healthy volunteers(n = 83).The association between serum levels of GROβ and clinical parameters of ESCC was analyzed statistically.RESULTS:The serum GROβ levels were much higher in ESCC patients than in healthy controls(median:645 ng/L vs 269 ng/L,P < 0.05).Serum GROβ levels were correlated positively with tumor size,lymph node metastasis,and tumor-node-metastasis(TNM) staging,but not with gender or the histological grade of tumors in ESCC patients.The sensitivity and specificity of the assay for serum GROβ were 73.61% and 56.63%,respectively.CONCLUSION:GROβ may function as an oncogene product and contribute to tumorigenesis and metastasis of ESCC.

Elevated serum levels of human relaxin-2 in patients with esophageal squamous cell carcinoma

AIM: To assess the prognostic value of serum human relaxin 2 (H2 RLN) level in patients with esophageal squamous cell carcinoma (ESCC). METHODS: From October 1998 to September 2009, 146 patients with histopathologically confirmed ESCC were enrolled in this study. One hundred patients underwent en bloc esophagectomy, and 46 patients with unresectable tumors underwent palliative surgery. Five of the 146 patients died of surgical complications. Serum levels of H2 RLN were measured by enzyme linked immunosorbent assay. The relationship between serum H2 RLN level and each of the clinicopathological parameters was analyzed using the χ2 test. Patients were classified into two groups according to their H2 RLN level (< 0.462 ng/mL vs ≥ 0.462 ng/mL). When any analysis cell had fewer than five cases, the Fisher's exact test was used. The statistical difference between groups A and B in each clinicopathological category was determined by the Student's t test (two-tailed) or analysis of variance. Survival curves were plotted using the Kaplan-Meier method. The statistical difference in survival between the different groups was compared using the log-rank test. Survival correlation with the prognostic factors was further investigated by multivariate analysis using the Cox proportional hazards model with backward stepwise likelihood ratio. RESULTS: ESCC patients tended to have significantly higher serum H2 RLN concentrations (0.48 ± 0.17 ng/ mL, n=141) compared with the healthy control group (0.342 ± 0.12 ng/mL, n=112). There was a significant difference between patients with lymph node involvement (0.74 ± 0.15 ng/mL, n=90), distant metastasis (0.90 ± 0.19 ng/mL, n=32) and those without lymph node involvement (0.45 ± 0.12 ng/mL, n=51), and distant metastasis (0.43 ± 0.14 ng/mL, n=109), respectively (P < 0.01). Patients with high H2 RLN levels (≥ 0.462 ng/mL) had a poorer prognosis than patients with low serum H2 RLN levels (< 0.462 ng/mL; P=0.0056). The H2 RLN level was also correlated with survival and tumor-node-metastasis staging, but not with age, tumor size, gender, lymphovascular invasion or the histological grade of tumors. Cox regression analysis showed that H2 RLN was an independent variable. CONCLUSION: Serum concentrations of H2 RLN are frequently elevated in ESCC patients and are correlated with disease metastasis and survival. Serum concentrations of H2 RLN may be an important prognostic marker in ESCC patients.

MicroRNA and esophageal carcinoma

Objective：An abundant class of non-coding small RNA molecules, 21-25 nucleotide in length, are widely found in animals and plants and named microRNA （miRNA）. MiRNAs are highly evolutionarily conserved, expressing in specific tissue and timing, and negatively regulate the gene expressions at the posttranscriptional level,and subsequently control crucial physiological processes such as metabolism, amplification, differentiation, development and apoptosis, Therefore, miRNAs could provide an access to many human diseases in theory. Recent evidence demonstrates that miRNAs play an important role in the initiation and progression of human cancer, mainly by interrupting the cell cycle at the cellular level and by interacting with signaling The expression profiling of miRNAs can be used as a tool of diagnosis, staging, prognosis and biotherapy of some tumors, as has already been proven to have superiority to mRNA, in the categorization of tumors. This review focuses on the genesis, mechanism of action of miRNA and its relationship to tumors, detection methods and its potential effect on the diagnosis, staging, and biotherapy in esophageal carcinoma.

Impact and Analysis of Prognostic Factors in Patients with Non-Metastatic Esophageal Squamous Cell Carcinoma: A Retrospective Single Institution Study

Objective: To investigate the impact of local tumor factors on the prognosis of non-metastatic esophageal squamous cell carcinoma patients. Methods: We performed a retrospective analysis of data from 278 consecutive esophageal squamous cell carcinoma patients between January 2009 and December 2016. The prognosis factors such as the GTV volume, GTV maximum diameter, and GTV length were analyzed. Results: The results of ROC curve analysis showed that prognosis critical values of the GTV volume, GTV maximum diameter, and GTV length were 27.98 cm3, 1.80 and 5.85 cm, respectively. The result of the univariate analysis showed that the GTV volume (P = 0.0184), GTV maximum diameter (P = 0.0246), and GTV length (P = 0.0035) were the prognostic factors for overall survival;the barium meal length (P = 0.0149) was the prognostic factor for local control. The multivariate analysis showed that the barium meal length (P = 0.0013), GTV maximum diameter (P = 0.0047), and GTV length (P = 0.0032) as the independent prognostic factors associated with overall survival;the barium meal length (P = 0.0037) was the only independent prognostic factors for local control. Conclusion: The esophageal lesion length was the main prognosis factor for patients with non-metastatic esophageal squamous cell carcinoma. Therefore, we suggest that the physician must give enough attention to these patients in clinical practice, and give active treatment.

IDENTIFICATION OF A NEW HUMAN nm23 GENE,nm23-H3b

Nm23 is a kind of effective tumor metastasis suppressor genes which included two types in human:nm23-H1 and nm23-H2. Amino acid identity between nm23-H1 and nm23-H2 was 88%.In this study,using a pair of primers to flank the part of coding sequence of nm 23,the 5'-translated sequence was amplified by polymerase chain reaction (PCR) from human normal liver genomic DNA.A 375-base pairs clone was charactertzed,which designated pnm23-H3b.The nm23-H3b nucleotide sequence between 40 bp and 70 bp is different from nm23-H1 and nm23-H2,and other sequences have 86%and 90%identical to nm23-H1 and nm23-H2,respectively.Southern blot containing BglⅡ-digested human liver genomic DNA hybridized to the entire nm23-H3b DNA and showed three bands at 10.5,7.9 and 4.0 Kb.These data demonstrate that the third human nm23 exists possibly.Therefore,nm23 may be considered a family of closely related genes.

基于生物信息学探讨赖氨酸氧化酶在食管癌原发灶中的表达及对骨转移患者预后的影响

目的基于生物信息学探讨赖氨酸氧化酶(Lox)在食管癌(ESCA)原发灶及骨转移灶中的表达及临床意义。方法通过癌症基因组图谱(TCGA)及基因表达谱分析互动平台(GEPIA)数据库筛选ESCA与正常食管组织中差异表达的基因。筛选2016年1月—2020年12月河北医科大学第四医院收治的食管癌手术患者的随访信息,收集在随访过程中确诊骨转移患者的临床资料。应用蛋白免疫印迹(Western blot)验证Lox在ESCA及正常食管组织中的表达;通过免疫组化染色检测人ESCA组织、正常组织中Lox的表达;应用Kaplan-Meier曲线及Cox回归探索Lox的表达对于生存期的影响。结果对GEPIA及TCGA数据库有关ESCA数据分析发现,Lox在ESCA病灶中的表达高于正常组织,差异有统计学意义(P<0.05);应用京都基因与基因组百科全书(KEGG)及基因富集分析(GO)发现,Lox可能参与多种信号通路的信息传导;Western blot结果显示,癌组织中Lox表达高于癌旁正常组织,差异有统计学意义(P<0.05);对随访资料的分析发现,Lox高表达患者更倾向于发生多发骨转移;生存分析发现Lox高表达患者无骨转移生存期和总生存期短于Lox低表达的患者,差异有统计学意义(P<0.05);Cox回归发现Lox是食管癌骨转移患者预后的独立危险因素。结论Lox在ESCA中呈高表达,并与临床预后相关,其可作为ESCA诊断及治疗的有效靶点。

食管鳞癌患者血清IL-23和MMP-9的相关性及其临床意义

目的:探讨食管鳞癌患者血清IL-23和MMP-9的表达水平以及两者的相关性和临床意义。方法:选取经病理确诊的食管鳞癌患者48例和同期胃镜活检结果良性的体检者30例。采用酶联免疫吸附法(ELISA)检测两组血清IL-23和MMP-9的表达水平,并进一步分析两者的相关性。结果:鳞癌组血清IL-23和MMP-9表达水平均高于对照组(t=26.66,16.89,P<0.05),且血清IL-23和MMP-9的表达呈正相关关系(r=0.790,P<0.05),血清IL-23表达水平与TNM分期、淋巴结有无转移和分化程度(高、中分化与低分化)有关,P值分别为0.040、0.042和0.038。结论:IL-23的高表达与食管鳞癌的发生发展密切相关。IL-23可能通过上调MMP-9的表达参与食管鳞癌的侵袭与转移。