Background: Patients with esophageal cancer (EC) frequently have multiple primary cancers. We conducted the present study to assess the risk of multiple primary malignancies for patients with squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus and to investigate the influence of multiple primary tumors on the prognosis of EC patients. Methods: Using the data of 44,091 EC patients from the Surveillance Epidemiology and End Results (SEER) database, we calculated the standardized incidence ratios (SIRs) for overall multiple primary cancers and cancers at particular sites among EC survivors. The SIRs of esophageal SCC and AC patients were compared using Poisson regression. The Kaplan-Meier (KM) method was used for survival analysis. Results: Multiple primary cancer risk was significantly increased among both esophageal SCC and AC survivors (SIR: 2.28 and 1.57, respectively; P<0.001). Among SCC patients, the highest SIRs were found in the oral cavity and pharynx (SIR: 16.54), esophagus (SIR: 10.02), and larynx (SIR: 10.34). Also, the highest SIRs following AC cases were observed in the esophagus (SIR: 8.81), stomach (SIR: 9.29), and small intestine (SIR: 4.95). SIRs for the oral cavity and pharynx, lung, and larynx were significantly higher among SCC survivors than AC survivors (all P<0.05). KM analysis revealed no significant difference of overall survival (OS) for multiple primary cancers, including those of the esophagus, stomach, oral cavity and pharynx, and lung among EC patients (log rank =2.04; P=0.564), except for prostate cancer (log rank =96.65; P<0.001). Conclusions: Multiple primary malignancy risk differed by the histological type of esophageal SSC and AC survivor. However, no significant relationship between survival and the multiple primary cancer sites, except for prostate cancer, was observed.

Background Although previous studies have discussed whether the minimally invasive esophagectomy (MIE) is superior to open surgery, the data concerning esophageal squamous cell carcinoma (ESCC) patients underwent neoadjuvant treatment followed by radical resection is limited. The purpose of our study was to compare the short- and long-term clinical outcomes of the two surgical approaches in treating ESCC patients. Methods Between January 2010 and December 2016, ESCC patients who had received neoadjuvant therapy and underwent Mckeown esophagectomy at our institute were eligible. The baseline characteristics, pathological data, short-and long-term outcomes of these patients were collected and compared based on the surgical approach. Results A total of 195 patients was included in the current study. Compared to patients underwent open surgery, patients underwent MIE had shorter operative time and less intraoperative bleeding (390 min vs 330 min, P = 0.001; 204 ml vs 167 ml, P = 0.021). In addition, the risk of anastomotic leakage was decreased in MIE group (20.0% vs 3.3%, P < 0.001), while the occurrence of other complications did not have statistical significance between two groups. Overall survival (OS) and disease-free survival (DFS) was no difference in patients received neoadjuvant chemotherapy between the two approaches. For the patients underwent neoadjuvant chemoradiotherapy, OS was significantly better in the MIE group (log rank = 6.197; P = 0.013). Conclusion Minimally invasive Mckeown esophagectomy is safe and feasible for ESCC patients who underwent neoadjuvant therapy. MIE approach presented better perioperative results than open esophagectomy. The effect of surgical approaches on survival was depending on the scheme of neoadjuvant treatment.

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Esophageal squamous cell carcinoma (ESCC) is the major histological type of esophageal cancers worldwide. Transcription factor PTTG1 was seen highly expressed in a variety of tumors and was related to the degree of tumor differentiation, invasion, and metastasis. However, the clinical significance of PTTG1 had yet to be verified, and the mechanism of abnormal PTTG1 expression in ESCC was not clear. In this study, the comprehensive analysis and evaluation of PTTG1 expression in ESCC were completed by synthesizing in-house immunohistochemistry (IHC), clinical sample tissue RNA-seq (in-house RNA-seq), public high-throughput data, and literature data. We also explored the possible signaling pathways and target genes of PTTG1 in ESCC by combining the target genes of PTTG1 (displayed by ChIP-seq), differentially expressed genes (DEGs) of ESCC, and PTTG1-related genes, revealing the potential molecular mechanism of PTTG1 in ESCC. In the present study, PTTG1 protein and mRNA expression levels in ESCC tissues were all significantly higher than in non-cancerous tissues. The pool standard mean difference (SMD) of the overall PTTG1 expression was 1.17 (95% CI: 0.72–1.62, P &lt; 0.01), and the area under curve (AUC) of the summary receiver operating characteristic (SROC) was 0.86 (95% CI: 0.83–0.89). By combining the target genes displayed by ChIP-seq of PTTG1, DEGs of ESCC, and PTTG1-related genes, it was observed that PTTG1 may interact with these genes through chemokines and cytokine signaling pathways. By constructing a protein–protein interaction (PPI) network and combining ChIP-seq data, we obtained four PTTG1 potential target genes, SPTAN1, SLC25A17, IKBKB, and ERH. The gene expression of PTTG1 had a strong positive correlation with SLC25A17 and ERH, which suggested that PTTG1 might positively regulate the expression of these two genes. In summary, the high expression of PTTG1 may play an important role in the formation of ESCC. These roles may be completed by PTTG1 regulating the downstream target genes SLC25A17 and ERH.

These authors contributed equally to this workObjective: The impact of negative lymph nodes (NLNs) count on prognosis in esophageal cancer (EC) was analyzed using two institutions surgical database. Methods: We conducted a retrospective study of 768 EC patients treated by surgical resection between January 2010 and December 2012. The effects of the NLNs count on prognosis was analyzed. Cox regression model was conducted to determine the significant prognostic elements. Results: The number of NLNs was studied as a categorical variable based on the quartiles (Q1: ≤15, Q2: 16-21, Q3: 22-30, Q4: ≥31). And a better overall survival (OS) was observed with increasing number of NLNs (HR= 0.762; 95% CI, 0.596-0.974 for Q2, HR= 0.666; 95% CI, 0.516-0.860 for Q3 and HR= 0.588; 95% CI, 0.450-0.768 for Q4) (all P<0.05).Multivariate regression analysis revealed that the NLNs count was an independent prognostic factor. Besides, for patients in T2 or T3 stage, a high number of NLNs was found to be significantly associated with a favorable OS (log rank P<0.001). Conclusion: A higher number of NLNs is independently related to the better OS in EC patients after surgical resection.

Esophageal cancer (ESCA) is a common malignancy in the digestive system with a high mortality rate and poor prognosis. Tumor microenvironment (TME) plays an important role in the tumorigenesis, progression and therapy resistance of ESCA, whereas its role in predicting clinical outcomes has not been fully elucidated. In this study, we comprehensively estimated the TME infiltration patterns of 164 ESCA patients using Gene Set Variation Analysis (GSVA) and identified 4 key immune cells (natural killer T cell, immature B cell, natural killer cell, and type 1 T helper cell) associated with the prognosis of ESCA patients. Besides, two TME groups were defined based on the TME patterns with different clinical outcomes. According to the expression gene set between two TME groups, we built a model to calculate TMEscore based on the single-sample gene-set enrichment analysis (ssGSEA) algorithm. TMEscore systematically correlated the TME groups with genomic characteristics and clinicopathologic features. In conclusion, our data provide a novel TMEscore which can be regarded as a reliable index for predicting the clinical outcomes of ESCA.

This study aimed to investigate the clinicopathological significance and prospective molecular mechanism of RUNX family transcription factor 2 (RUNX2) in lung squamous cell carcinoma (LUSC). The authors used immunohistochemistry (IHC), RNA-seq, and microarray data from multi-platforms to conduct a comprehensive analysis of the clinicopathological significance and molecular mechanism of RUNX2 in the occurrence and development of LUSC. RUNX2 expression was significantly higher in 16 LUSC tissues than in paired non-cancerous tissues detected by IHC (P < 0.05). RNA-seq data from the combination of TCGA and genotype-tissue expression (GTEx) revealed significantly higher expression of RUNX2 in 502 LUSC samples than in 476 non-cancer samples. The expression of RUNX2 protein was also significantly higher in pathologic T3-T4 than in T1-T2 samples (P = 0.031). The pooled standardised mean difference (SMD) for RUNX2 was 0.87 (95% CI, 0.58-1.16), including 29 microarrays from GEO and one from ArrayExpress. The co-expression network of RUNX2 revealed complicated connections between RUNX2 and 45 co-expressed genes, which were significantly clustered in pathways including ECM-receptor interaction, focal adhesion, protein digestion and absorption, human papillomavirus infection and PI3K-Akt signalling pathway. Overexpression of RUNX2 plays an essential role in the clinical progression of LUSC.

The purpose of this study is to investigate the significance of alpha-enolase (ENO1) expression in squamous cell carcinoma of the lung (LUSC), its prognostic value, and prospective molecular mechanism. Using multiplatforms data, including in-house immunohistochemistry, in-house real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), in-house microarray, and public high-throughput data, the expression significance and prognostic role of ENO1 in LUSC tissues were analyzed comprehensively. With the combination of all eligible cases, compared with 941 non-LUSC lung tissues, ENO1 was significantly overexpressed in 1163 cases of LUSC (standardized mean difference (SMD) = 1.23, 95% confidence interval (CI) = 0.76–1.70, P  < 0.001). ENO1 also displayed a great ability to differentiate LUSC tissues from non-LUSC lung tissues (AUC = 0.8705) with the comprehensive sensitivity being 0.88 [0.83–0.92], and comprehensive specificity being 0.89 [0.84–0.94]). Moreover, in 1860 cases of LUSC with survival information, patients with higher expression of ENO1 had poorer prognosis (hazard ratio (HR) = 1.20, 95% CI = 1.01–1.43, P  = 0.043). ENO1 and its related genes mainly participated in the pathways of cell division and proliferation. In conclusion, the upregulation of ENO1 could affect the carcinogenesis and unfavorable outcome of LUSC.