1.Clinical Medicine Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830054, China; 2.the First Department of Pediatric Surgery, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830054, China;
3.Department of Thoracic Surgery, the First Affiliated Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Urumqi 830054, China
Abstract：Objective To investigate the expression of hMSH2 and FHIT genes in Kazakh esophageal squamous cell carcinoma, and analyze the correlation between gene expression and its clinicopathological significance. Methods Esophageal cancer and its adjacent normal tissue specimens were selected from 43 patients who underwent radical resection of esophageal cancer in the First Affiliated Hospital of Xinjiang Medical University from May 2013 to May 2017. qRT-PCR method was used on 30 cases, while immunohistochemistry was conducted on 43 cases to study their clinicopathological characteristics. Results The mRNA expression levels of both hMSH2 and FHIT genes in esophageal squamous cell carcinoma tissues were significantly lower than those in adjacent normal tissues, and the differences were statistically significant (P ＜ 0.05). Results of immunohistochemistry showed that the positive expression rate of hMSH2 and FHIT protein in esophageal squamous cell carcinoma tissues was significantly lower than that in adjacent normal tissues, and the difference was statistically significant (P ＜ 0.05). The expression level of HMSH2 protein was related to the degree of tumor differentiation, lymph node metastasis and postoperative pathological stage (P ＜ 0.05), while it had nothing to do with the age, sex and tumor location of the patients with esophageal cancer (P ＞ 0.05). The expression level of FHIT was only related to the depth of infiltration (P ＜ 0.05). Kaplan-Meier survival analysis found that the expression level of HMSH2 in esophageal cancer was correlated with survival rate (P ＜ 0.05). The results of COX multivariate survival analysis showed that the loss of hMSH2 gene expression and the degree of tumor differentiation were independent risk factors for poor prognosis in Kazakh patients with esophageal squamous cell carcinoma (P ＜ 0.05). Conclusion hMSH2 and FHIT may be involved in the occurrence and development of Kazakh esophageal cancer, so the detection of co-expression could be used as an important indicator for prognosis.
[1] Karamanou M，Markatos K，Papaioannou TG，et al. Hallmarks in history of esophageal carcinoma [J]. J BUON，2017，22（4）：1088-1091.
[2] Bray F，Ferlay J，Soerjomataram I，et al. Global Cancer Statistics 2018：GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries [J]. CA Cancer J Clin，2018，68（6）：394-424.
[3] 师小博，孙宁晨，龚拓拓，等.食管鳞癌放射敏感性及预后的基因组学预测分析：基于生物信息学分析的证据[J].西安交通大学学报：医学版，2020，41（5）：651-658.
[4] Lin Y，Totsuka Y，He Y，et al. Epidemiology of Esophageal Cancer in Japan and China [J]. J Epidemiol，2013，23（4）：233-242.
[5] Chen W，Zheng R，Baade PD，et al. Cancer statistics in China，2015 [J]. Ca Cancer J Clin，2016，66（2）：115-132.
[6] Klingelh?觟fer D，Zhu Y，Braun M，et al. A world map of esophagus cancer research：a critical accounting [J]. J Transl Med，2019，17（1）：150.
[7] Wang JB，Ma DL，Li JY，et al. Association between expression of DNA mismatch repair genes and clinical features and prognosis of patients with radical resection of colon cancer [J]. Genet Mol Res，2016，15（3）.
[8] Tamoto A，Yashima K，Hosoda K，et al. Protein expression of Fragile Histidine Triad and cyclooxgenase-2 in serrated neoplasia of the colorectum [J]. Oncol Lett，2017，14（3）：3683-3688.
[9] Vageli DP，Zaravinos A，Daniil Z，et al. hMSH2 and hMLH1 gene expression patterns differ between lung adenocarcinoma and squamous cell carcinoma：correlation with patient survival and response to adjuvant chemotherapy treatment [J]. Int J Biol Markers，2013，27（4）：e400-4.
[10] Chen Y，Wang X，Li F，et al. Relationship between expression of P27，Fragile Histidine Triad （FHT），phosphatase and tensin homolog deleted on chromosome ten （PTEN），P73，and prognosis in esophageal squamous cell carcinoma [J]. Ann Diagn Pathol，2015，19（1）：33-36.
[11] Hosoda K，Yashima K，Tamoto A，et al. Expression of methylation-modulated tumor-related genes in endoscopically resected early esophageal squamous neoplasia [J]. Oncol Lett，2017，14（1）：737-742.
[12] Hu N，Kadota M，Liu H，et al. Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer [J]. Cancer Res，2016，76（7）：1714-1723.
[13] 张德庆，陈东育，宋兆峰.FHIT蛋白及mRNA在食管癌组织中的表达及意义[J].中国实验诊断学，2011，15（1）：83-85.
[14] Amin MB，Greene FL，Edge SB，et al. The Eighth Edition AJCC Cancer Staging Manual：Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging [J]. CA Cancer J Clin，2017， 67（2）：93-99.
[15] Su Y，Yin L，Liu R，et al. Promoter methylation status of MGMT，hMSH2，and hMLH1 and its relationship to corresponding protein expression and TP53 mutations in human esophageal squamous cell carcinoma [J]. Med Oncol，2014，31（2）：784.
[16] Ohta M，Inoue H，Cotticelli MG，et al. The FHIT gene，spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t（3；8） breakpoint，is abnormal in digestive tract cancers [J]. Cell，1996，84（4）：587-597.
[17] Ma K， Cao B，Guo M，et al. The detective，prognostic，and predictive value of DNA methylation in human esophageal squamous cell carcinoma [J]. Clin Epigenetics，2016，8：43.
[18] Hayashi A，Yashima K，Takeda Y，et al. Fhit，E-cadherin，p53，and Activation-Induced Cytidine Deaminase Expression in Endoscopically Resected Early Stage Esophageal Squamous Neoplasia [J]. J Gastroenterol Hepatol，2012，27（11）：1752-8.
[19] 赵阿红，宋一民，尹玉慧，等.食管鳞癌组织中FHIT和MSH2 mRNA的检测与分析[J].中国实用医刊，2009，36（24）：94-95.
[20] Bekar A，Ce?觭ener G，Tunca B，et al. Investigation of Mutations and Expression of the FHIT Gene in Turkish Patients With Brain Metastases Derived From Non-Small Cell Lung Cancer [J]. Tumori，2007，93（6）：604-607.
[21] Ainiwaer J，Tuerhong A，Hasim A，et al. Association of the Plasma Riboflavin Levels and Riboflavin Transporter （C20orf54）Gene Statuses in Kazak Esophageal Squamous Cell Carcinoma Patients [J]. Mol Biol Rep，2013， 40（5）：3769-3775.
[22] Kelimu A，Anwer J，Yanchao D，et al. Tissue riboflavin levels and C20orf54 protein expression are regulated by C20orf54 hypermethylation in Kazaks esophageal cancer [J]. Int J Clin Exp Pathol，2016，9（2）2643-2649.
[23] Feng RM，Zong YN，Cao SM，et al. Current cancer situation in China：good or bad news from the 2018 Global Cancer Statistics? [J]. Cancer Commun （Lond），2019，39（1）：22.
[24] Yamamoto S，Yashima K，Kawata S，et al. Frequent aberrant p53 and Fhit expression in endoscopically resected superficial hypopharyngeal cancer and esophageal cancer [J]. Oncol Lett，2017，14（1）：587-592.
[25] Ling ZQ，Li P，Ge MH，et al. Aberrant methylation of different DNA repair genes demonstrates distinct prognostic value for esophageal cancer [J]. Dig Dis Sci，2011， 56（10）：2992-3004.
[26] Sarli L，Bottarelli L，Azzoni C，et al. Abnormal Fhit protein expression and high frequency of microsatellite instability in sporadic colorectal cancer [J]. Eur J Cancer，2004，40（10）：1581-1588.
京公网安备 11010502046598号