BackgroundThis study was intended to construct a brand new prognostic nomogram after combine clinical and pathological characteristics to increases prognostic value in patients with esophageal squamous cell carcinoma.MethodsA total of 1,634 patients were included. Subsequently, the tumor tissues of all patients were prepared into tissue microarrays. AIPATHWELL software was employed to explore tissue microarrays and calculate the tumor-stroma ratio. X-tile was adopted to find the optimal cut-off value. Univariate and multivariate Cox analyses were used to screen out remarkable characteristics for constructing the nomogram in the total populations. A novel prognostic nomogram with clinical and pathological characteristics was constructed on the basis of the training cohort (n=1,144). What’s more performance was validated in the validation cohort (n=490). Clinical-pathological nomogram were assessed by concordance index, time-dependent receiver operating characteristic, calibration curve and decision curve analysis.ResultsThe patients can divide into two groups with cut-off value of 69.78 for the tumor-stroma ratio. It is noteworthy that the survival difference was noticeable (P<0.001). A clinical-pathological nomogram was constructed by combining clinical and pathological characteristics to predict the overall survival. In comparison with TNM stage, the concordance index and time-dependent receiver operating characteristic of the clinical-pathological nomogram showed better predictive value (P<0.001). High quality of calibration plots in overall survival was noticed. As demonstrated by the decision curve analysis, the nomogram has better value than the TNM stage.ConclusionsAs evidently revealed by the research findings, tumor-stroma ratio is an independent prognostic factor in patients with esophageal squamous cell carcinoma. The clinical-pathological nomogram has an incremental value compared TNM stage in predicting overall survival.

目的 观察早期贲门癌患者根治术后5年生存情况及死亡原因,探讨术后5年死亡的危险因素.方法 2 035例早期贲门癌患者均行贲门癌根治术(R0 切除)并随访至2022年3月,采用Kaplan-Meier法分析5年生存概率,统计术后5年死亡原因.术后5年因肿瘤复发/转移死亡474例为死亡组,生存患者1 516例为生存组,采用Cox比例风险回归模型分析早期贲门癌患者根治术后5年因肿瘤复发/转移死亡的危险因素.结果 2 035例患者术后1、2、3、4、5年生存概率分别为94.1％、87.5％、80.8％、75.1％和69.8％.截至2022年3月,2 035例患者死亡801例,其中术后5年死亡519例(64.8％).519例中,死于贲门癌复发/转移474例(91.3％),心脑血管疾病13例(2.5％),术后并发症10例(1.9％),其他疾病9例(1.7％),自杀3例(0.6％),意外2例(0.4％),自然死亡2例(0.4％),原因不详6例(1.2％);术后 1、2、3、4、5 年死亡率分别为 22.5％(117/519)、23.7％(123/519)、21.4％(111/519)、17.1％(89/519)、15.2％(79/519).年龄＞60 岁(HR=1.423,95％CI:1.182～1.712,P＜0.001)、肿瘤浸润程度为 T2(HR=1.469,95％CI:1.223～1.765,P＜0.001)是早期贲门癌患者根治术后5年因肿瘤复发/转移死亡的危险因素.结论 早期贲门癌患者5年生存概率为69.8％,术后5年死亡的主要原因为肿瘤复发/转移;年龄＞60岁、较深肿瘤浸润程度是早期贲门癌患者根治术后5年死亡的独立危险因素.

目的:分析1995 至2021 年河南省食管癌高发区5 家医院就诊病例中早期食管癌占比的变化,了解高发区食管癌的防治效果.方法:对来自河南省食管癌高发区27a间5 家医院收治且有明确病理诊断的127 249 例食管癌病例中早期癌占比进行Joinpoint回归分析.结果:2009 年食管癌病例数较1995 年增加了2.4 倍,而2009 年至2021 年病例数则逐年下降.Joinpoint分析结果显示,1995 至2011 年早期食管癌占比上升速度较慢,年度变化百分比(95%CI)为 2.94%(1.53%～4.36%);2011 年以后则上升速度增快,年度变化百分比(95%CI)为 12.27%(9.27%～15.35%).结论:食管癌一级预防和二级预防措施的推广使高发区食管癌病例数明显减少,早期癌检出率大幅度提升.

目的:探讨早期食管鳞状细胞癌(鳞癌)短期生存预后的影响因素.方法:回顾性分析9699例早期(Tis～T1N0M0)食管鳞癌患者的临床病理资料,采用Logistic回归分析筛选5 a、1 a生存预后的影响因素.结果:生存期<5 a者2713例(28.0％),<1 a者567例(6.6％).男性、年龄>65岁、肿瘤长径>5 cm、大体类型为斑块型和糜烂型是5 a和1 a生存的危险因素(P<0.05).有脉管癌栓是5 a和1 a生存的危险因素,OR(95％CI)分别为2.841(2.051～3.934)、1.767(1.087～2.871);肿瘤家族史阳性则是5 a和1 a生存的保护性因素,OR(95％CI)分别为0.819(0.741～0.906)、0.765(0.635～0.920).黏膜下层浸润是5 a生存的危险因素,OR(95％CI)为1.259(1.126～1.407);但是1 a生存的保护性因素,OR(95％CI)为0.820(0.677～0.994).结论:性别、年龄、肿瘤家族史、肿瘤长径、大体类型、浸润程度、脉管癌栓是早期食管鳞癌短期生存的重要影响因素.

目的:阐明1973-2020年中国食管鳞状细胞癌(ESCC)TNM分期分布的变化特征.方法:162814例ESCC病例来自郑州大学第一附属医院省部共建食管癌防治国家重点实验室建立的50万例食管/贲门癌患者临床信息数据库,均接受食管癌根治术治疗,TNM分期参照第6版AJCC/UICC标准.比较不同临床特征患者TNM分期的分布.采用Joinpoint回归分析总体、男性、女性早期(0+Ⅰ期)癌患者占比的变化趋势,报告年度变化百分比(APC)、全局平均年度变化百分比(AAPC)及其95％CI.结果:162814例中,早期癌占10.7％;女性早期癌比例高于男性(12.1％vs 10.0％),高发区0、Ⅰ、Ⅱ期患者比例高于低发区,城镇0、Ⅰ、Ⅲ期患者比例高于农村,男、女性中青年患者(<50岁)早期癌占比均低于年龄≥50岁的患者(P<0.05).48 a间,总体患者和女性患者早期癌占比在2015-2020年升高最为快速,APC(95％CI)分别为27.8％(18.1％ ～38.2％)和28.9％(14.4％ ～45.1％),男性患者早期癌占比在2014-2020年升高最为快速,APC(95％CI)为22.2％(12.5％ ～32.7％);48 a间,总体、男性、女性患者中早期癌占比均呈升高趋势(P<0.05),AAPC(95％CI)分别为2.8％(1.3％ ～4.4％)、3.6％(2.3％ ～5.0％)、2.8％(1.2％ ～4.4％).结论:我国早期ESCC占比呈明显升高趋势,但是占比仍低于中晚期.食管癌早期发现筛查技术仍是食管癌研究领域亟待解决的关键科学问题.

Keratin pearls (KP) is an important indicator of the degree of tumor cell differentiation of esophageal squamous cell carcinomas (ESCC). However, the independent prognostic value of KP in ESCC patients remains unclear. The hematoxylin-eosin (H&E) stained tissue microarrays (TMAs) or whole slides of the patients were prepared to identify the existence of KP. Kaplan-Meier (KM) survival analysis as well as univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of KP. A nomogram based on KP and other clinicopathologic characteristics was constructed. The C-index, calibration curve, Receiver Operating Characteristic (ROC) curve, and Decision Curve Analysis (DCA) were used to evaluate the nomogram. The results indicated KP is a protective factor against lymph node metastasis and is closely associated with the differentiation degree in ESCC patients. KM survival analysis showed that the overall survival (OS) of patients with KP was significantly better than for patients without KP. In addition, multivariate Cox regression analysis revealed that KP was an independent predictor of OS. Furthermore, ROC curve demonstrated that KP combined with differentiation degree could more accurately predict the 5-year survival rate than differentiation degree alone. Importantly, the nomogram showed good discrimination and calibration abilities in both training and validation groups, which could more accurately predict the 3-, 5-, and 10-year survival rates of ESCC patients and adds to the predictive value of TNM stage alone. In conclusion, KP is an independent predictor of prognosis in patients with ESCC and provides incremental prognostic value to degree of differentiation.

目的:探讨食管鳞状细胞癌(食管鳞癌)患者主诉与病理分期的关系.方法:85919例食管鳞癌病例均来自郑州大学第一附属医院省部共建食管癌防治国家重点实验室建立的50万例食管/贲门癌患者临床信息数据库,根据AJCC食管癌肿瘤淋巴结转移分期系统(第6版)进行病理分期,其中早期(0/Ⅰ期)8129例,中晚期(Ⅱ/Ⅲ/Ⅳ期)77790例.数量较少(<100例)的主诉不纳入研究.比较早中晚期患者首次就诊各类主诉的频率.将85919例随机分为10组,随机选取其中9组作为训练集,采用Logistic回归分析建立主诉对早中晚分期的预测模型;剩余1组作为测试集,通过绘制ROC曲线,对模型预测效能进行评价.结果:早期和中晚期患者吞咽哽噎、吞咽疼痛、腹部不适、胸骨疼痛、腹部疼痛、胸骨后不适、吞咽哽噎伴胸部疼痛、胸部疼痛、反酸和呃逆这10种主诉频率差异有统计学意义(P<0.001).以病理分期(早期为1,中晚期为0)为因变量,以上述差异主诉作为自变量(有=1,无=0),以性别、年龄、高低发区等特征作为调整因素,采用逐步法进行Logistic回归,结果吞咽哽噎(β=-1.906,P<0.001)、吞咽疼痛(β=-0.662,P<0.001)、胸骨疼痛(β=-0.219,P=0.005)、腹部疼痛(β=-0.392,P<0.001)、吞咽哽噎伴胸部疼痛(β=-2.069,P<0.001)、胸部疼痛(β=-0.742,P<0.001)、反酸(β=-0.562,P=0.001))和呃逆(β=-0.842,P<0.001)进入最终模型.该模型预测的ROC曲线下面积(95％CI)0.694(0.560～0.829).结论:多种主诉联合对食管鳞癌早中晚分期具有一定的预测价值.

Objective: There are no comprehensive studies on survival outcomes and optimal treatment protocols for cervical esophageal cancer (CEC), due to its rare clinical prevalence. Our objective was to determine the relationship between pathological characteristics, treatment protocols, and survival outcomes in Chinese CEC patients. Methods: A total of 500 Chinese CEC patients were selected from our 500,000 esophageal and gastric cardia carcinoma database (1973–2018). There were two main groups: patients treated with surgery, and patients receiving non-surgical treatments (radiotherapy, radiochemotherapy, and chemotherapy). The Chi-square test and Kaplan–Meier method were used to compare the continuous variables and survival. Results: Among the 500 CEC patients, 278 (55.6%) were male, and the median age was 60.9 ± 9.4 years. A total of 496 patients (99.2%) were diagnosed with squamous cell carcinoma. In 171 (34.2%) patients who received surgery, 22 (12.9%) had undergone laryngectomy. In 322 (64.4%) patients who received non-surgical treatments, 245 (76.1%) received radiotherapy. Stratified survival analysis showed that only T stage was related with survival outcomes for CEC patients in the surgical group, and the outcomes between laryngectomy and non-laryngectomy patients were similar. It was noteworthy that the 5-year survival rate was similar in CEC patients among the different groups treated with surgery, radiotherapy, chemotherapy, or radiochemotherapy (P = 0.244). Conclusions: The CEC patients had similar survival outcomes after curative esophagectomy and radiotherapy, including those with or without total laryngectomy. These findings suggest that radiotherapy could be the initial choice for treatment of Chinese CEC patients.

目的:探讨肿瘤家族史对贲门腺癌(GCA)患者术后预后的影响.方法:3 088例接受根治术治疗的GCA患者的临床、病理和随访信息取自河南省食管癌重点开放实验室50万例食管癌和贲门癌临床信息数据库.高发区2 315例,低发区773例.结果:在高发区,家族史阴性和阳性患者肿瘤长径、分化程度差异有统计学意义(P＜0.05);在低发区,家族史阴性和阳性患者肿瘤长径差异有统计学意义(P＜0.05).Cox回归分析结果显示,肿瘤家族史阳性是低发区GCA患者术后预后的独立保护因素[HR(95％ CI)=1.338(1.084～1.651)].结论:低发区肿瘤家族史可能是GCA患者术后预后的独立影响因素.

1959年,河南省委和省政府指派河南医学院等河南多家医疗单位的教学、科研和医务人员组成了河南医疗队[河南省林县食管癌防治研究协作组(后文简称协作组)]进驻林县(现改名为林州市)开展食管癌防治现场研究工作,至2019年已60年[1-2].期间,河南数代学者立足河南食管癌高发现场研究基地,围绕食管癌发生的危险因素、发生机制及防治,开展从基础到临床多学科交叉研究,取得一系列原创性研究成果,积累了丰富的食管癌高发现场防治研究经验.

目的:探讨早期与中晚期贲门腺癌(GCA)患者的术后预后影响因素.方法:从河南省食管癌重点开放实验室50万例食管癌和贲门癌临床信息数据库中收集5 596例GCA患者的资料.其中男4 321例,女1 275例;早、中、晚期患者分别有335、5 168和93例.患者均接受根治术治疗.结果:Cox分析结果显示,确诊年龄≥60岁(HR=3.069,95％ CI=1.167～5.625)、有癌栓(HR =3.137,95％ CI=1.063～9.253)是早期GCA患者术后预后的危险因素;男性(HR=1.090,95％ CI=1.002～1.185)、确诊年龄≥60岁(HR=1.409,95％ CI=1.312～1.531)、有癌栓(HR=1.299,95％ CI=1.167～1.446)、溃疡浸润型(HR=1.260,95％ CI=1.108～1.432)、中低分化(HR=1.167,95％ CI=1.103 ～ 1.344)、浸润程度深(HR=1.502,95％ CI=1.350～1.671)是中晚期GCA患者术后预后的危险因素.结论:确诊年龄≥60岁、有癌栓是所有病期GCA患者术后预后的独立危险因素,而男性、浸润溃疡型、低分化、浸润程度深是中晚期患者术后预后的独立危险因素.

Objective To compare the survival condition and related risk factors of the patients with ESCC between high-incidence area (HIA) and low-incidence area (LIA) of ESCC. Methods We collected the data of 38741 ESCC patients confirmed by pathology, among which, 23273 cases (60.1%) were from HIA and 15468 cases (39.9%) were from LIA. All patients underwent radical esophagectomy. Chi-square test was used to analyze the differences between groups of the patients with different clinicopathological characteristics, and Kaplan-Meier method was used to draw and Log rank test was used to assess the survival curves of the patients. Cox proportional hazards model was used to analyze the main influencing factors of survival. Results The proportion of male patients in LIA was higher than that in HIA (P < 0.001). The proportion of patients ≥50 years old in LIA was also higher than that in HIA (P < 0.001). ESCC patients in HIA had obviously better overall survival than patients in LIA (P < 0.001). HIA/LIA, gender, age at diagnosis, tumor location, differentiation, TNM stage and family history were independent factors for the survival of ESCC patients. Conclusion ESCC patients in HIA have obviously higher overall survival than those in LIA. LIA is an independent risk factor for poor survival of ESCC patients.

Nat. Genet. 42, 759–763 (2010); published online 22 August 2010; corrected after print 27 August 2014 In contrast to the version of this article initially published, the authors now find no evidence to support association with esophageal squamous cell carcinoma susceptibility for rs13042395[T] at 20p13 in their original data, in two independent sets of cases and controls collected in other Chinese populations or in the joint analysis of these three studies.

目的 探讨肿瘤体积对食管癌患者生存期的影响,加深对食管癌关键预后影响因素的了解.方法 通过入户或电话问卷调查及生存随访,采用卡方检验、Kaplan Meier生存曲线和Log Rank检验及COX生存分析模型,分析肿瘤体积≤6 cm3,6～18 cm3和≥18 cm3时对食管癌患者的生存期的影响.结果 成功随访5 723例(95.8％),其中男性3 666例,女性2 057例.随着肿瘤体积的增大患者生存期渐差(P=1.53E-13).女性体积≤6cm3患者明显多于男性,而体积≥18 cm3的患者明显少于男性(P＜0.05),女性患者生存期显著优于男性患者(P=4.24E-8).值得指出的是,青年组(≤50)体积≤6 cm3的患者少于中老年组,而体积≥18 cm3的患者明显多于中老年组(P ＜0.05),但青年患者生存期优于中老年患者(P=1.74E-9).淋巴结转移阳性组肿瘤体积≤6 cm3患者少于淋巴结转移阴性组(P＜0.05),生存期明显差于淋巴结转移阴性组(P=1.42E-59).随着浸润程度的加深,肿瘤体积增大(P =4.58E-23),患者生存期渐差(P=6.92E-16).COX多因素生存分析模型提示,肿瘤体积是影响食管癌患者生存期的独立因素(P =0.005).结论 随着肿瘤体积的增大患者生存期渐差,肿瘤体积是影响食管癌患者生存期的独立因素.

BACKGROUND:The role of tumor suppressor gene RASSF1A in the esophageal and gastric cardia carcinogenesis is still inconclusive. In this study, the polymorphism, promoter methylation and gene expression of RASSF1A were characterized in esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA).METHODS:We firstly analyzed the prevalence of RASSF1A A133S in a total of 228 cancer patients with ESCC (n=112) and GCA (n=116) and 235 normal controls by polymerase chain reaction (PCR) and restriction enzyme-digestion assay. Then, the promoter methylation status of the RASSF1A in ESCC (n=143), GCA (n=92) and corresponding adjacent normal tissues were further investigated using methylation-specific PCR (MSP) approach. Finally, the RASSF1A protein expression were determined in ESCC (n=27), GCA (n=24) and the matched adjacent normal tissues by immunohistochemical method.RESULTS:The frequency of 133Ala/Se and Ser/Ser genotype was significantly higher in GCA patients than in normal controls (19.0% vs. 10.2%, P=0.02). Compared with Ala/Ala genotype, Ala/Se and Ser/Ser genotype significantly increased susceptibility to GCA (OR=2.06, 95% CI=1.09-3.97). However, this polymorphism had no association with ESCC (P=0.69). The promoter methylation of RASSF1A gene was significantly increased the risk to both ESCC (OR=5.90, 95% CI=2.78-12.52) and GCA (OR=7.50, 95% CI= 2.78-20.23). Promoter methylation of RASSF1A gene in ESCC was also associated with age and cancer cell differentiation (for age: OR=3.11, 95% CI=1.10-8.73; for differentiation: OR=0.29, 95% CI=0.12-0.69). RASSF1A positive expression was significantly decreased the risk of GCA (OR=0.16, 95% CI=0.03-0.83). In contrast, there was no statistical significance between RASSF1A positive expression and ESCC. The expression of RASSF1A protein trend to be positively related with older GCA patients (OR=16.20, 95% CI=1.57-167.74).CONCLUSIONS:The present findings suggest that alterations of RASSF1A may play an important role in gastric cardia carcinogenesis in terms of polymorphism, promoter hypermethylation and protein expression. Whereas, RASSF1A hypermethylation may probably also be involved in esophageal squamous cell carcinogenesis.

Objective To compare the family history,clinical pathology and survival rate on the patients with concurrent esophageal squamous cell carcinoma(SCC) and gastric cardia adenocarcinoma(GCA)(CC patients) and the patients with either single SCC or GCA.Methods Home visit,questionnaire survey,hospital pathological check and telephone follow-up were performed in 1 011 patients with CC,2 095 patients with single SCC and 1 859 patients with single GCA.These patients came from the high incidence area of SCC and GCA at the junction of Henan,Hebei and Shanxi Provinces.SPSS 17.0 statistical software was used for,t-test,chi-square test,Kaplan-Meier survival analysis,Cox-regression model was used to analyze the relationship of family history,clinical pathology and survival rate between CC patients and single SCC or GCA patients.Results The positive family history rate of patients with CC was higher than those with single GCA(34%,27%,P0.05),but similar with that in the single SCC patients(34%,31%,P0.05).The early SCC and GCA from CC was more common in those with single SCC(27%∶15%) and GCA(18%,4%,P0.05).The patients with CC had shorter survival time than those with single SCC and GCA(P0.05),the mortality risk for CC was 2 folds and 3 folds higher than in those with single SCC(P0.05,HR=1.976) and GCA patients(P0.05,HR=2.652).Conclusion The hereditary susceptibility of CC patients is higher than the single SCC/GCA patients.The CC patients have shorter survival time than those with single SCC/GCA.

The group 2 LIM domain protein, Cysteine-rich intestinal protein 2 (CRIP2) was found to play an important role in esophageal squamous cell carcinoma (ESCC) tumorigenesis. Subcellular fractionation studies show that CRIP2 is expressed in the nucleus. Real-time quantitative PCR shows CRIP2 expression is down-regulated in ESCC tissues and cell lines. Functional studies reveal that CRIP2 reduces colony formation, growth, and invasion abilities. Furthermore, over-expression of CRIP2 induces apoptosis through induction of active caspases 3 and 9 proteins. In conclusion, this study shows CRIP2 plays an important role in the development of ESCC.

Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10(-8), and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19-1.40) and P= 7.63 × 10(-10). An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.

Aim:To investigate the interactions between genetic and environmental factors on gastric cardia carcinogenesis by analyzing the pathological changes of gastric cardia biopsy tissues from momozygous twins at a high-incidence area for esophageal cancer in Henan.Methods:Monozygous twins with 30 years old were invited to attend the mass survey with epidemiological questionnaire,endoscopic,biopsy and histopathological examinations.Results:Out of the 112 twins,6 cases of gastric cardia adenocarcinoma(GCA)were identified,and the incidence rate with consistent and inconsistent GCA was 0.9%(1/112)and 3.6%(4/112),respectively;two members of 45(40.2%)pairs of twins had the similar histopathological changes,and two members of 67(59.8%)pairs of twins were inconsistent in histopathological changes(Kappa=0.135,P=0.016).Conclusion:The present results demonstrate that GCA is the common sequence of environment and heredity,but environmental factor may have a larger contribution in gastric cardia carcinogenesis.

We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.