Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy known for its aggressive nature and poor prognosis. The present study aimed to investigate the expression levels and clinical importance of the Zic family member 5 (ZIC5) gene in ESCC. Gene expression data and survival information obtained from The Cancer Genome Atlas and Gene Expression Omnibus were utilized. In 176 patients with surgically resected ESCC, immunohistochemical analysis was conducted to validate the expression of ZIC5 protein in cancerous and adjacent tissues. The findings of the present study revealed a significant upregulation of ZIC5 in ESCC compared with normal tissues (P<0.05), which was further corroborated by immunohistochemistry exhibiting a notable association between ZIC5 expression and clinical parameters such as tumor size, invasion depth, lymph node metastasis and TNM staging (P<0.05). Survival analysis further indicated that high ZIC5 expression was an independent prognostic factor for poor outcomes in patients with ESCC (hazard ratio=1.519; 95% CI: 1.017-2.269; P<0.05). In addition, bioinformatic analyses predicted that hsa-microRNA-212-5p may regulate ZIC5 mRNA and gene enrichment analysis suggested that ZIC5 may facilitate ESCC progression through involvement in the cell cycle and DNA repair pathways. In conclusion, ZIC5 is highly expressed in ESCC and associated with a poor prognosis, indicating its potential as a therapeutic target and biomarker for ESCC management. Further studies are warranted to elucidate the precise mechanisms underlying the role of ZIC5 in ESCC progression.

Esophageal squamous cell carcinoma (ESCC) remains a lethal malignancy with a poor 5-year survival rate of approximately 20

To evaluate the efficacy and postoperative complications of endoscopic thoracoscopic and laparoscopic radical esophagectomy compared to open surgery in esophageal cancer treatment. This retrospective study included 103 esophageal cancer patients admitted from August 2018 to March 2022, divided into observation (endoscopic surgery) and control (open surgery) groups. We compared intraoperative parameters, postoperative outcomes, immune function, and one-year overall survival (OS). Intraoperative bleeding volume, the retention time of chest tube, postoperative fasting time, and hospital stay in the observation group were smaller than those in the control group (P < .05). The differences were not statistically significant (P > .05) when comparing operative time, the number of intraoperative blood transfusion cases, and the rate of operating room extubation in these 2 groups. The differences were not statistically significant when comparing the amount of resected lymph nodes and the positive rate of incisal edge in these 2 groups (P > .05). There was no statistically significant difference in the complication rates such as pneumonia, pleural effusion, pneumothorax, pulmonary embolism, anastomotic fistula, the leakage of thoracic duct, the injury of RLN and arrhythmia in these 2 groups (P > .05). At 7 days postoperatively, the CD4+ and CD4+/CD8+ in the observation group and the control group were smaller than the preoperative ones in their same groups, and they were larger in the observation group than those in the control group (P < .05); There was no statistically significant difference on the CD8+ in the observation group and the control group at 7 days postoperatively compared with the preoperative ones in their same groups (P > .05). The 1-year postoperative OS rate was 81.63% (40/49) in the observation group and 72.22% (39/54) in the control group, and the difference was not statistically significant when comparing the OS rates of these 2 groups (P = .238, HR = 0.622, 95% CI = 0.279-1.385). Endoscopic thoracoscopic and laparoscopic esophagectomy offers less invasive treatment with significant short-term benefits and better preservation of immune function in esophageal cancer patients, making it a safe and effective surgical option.

Background:Esophageal cancer (EC) remains a significant global health concern. Minimally invasive surgical techniques, including robot-assisted approaches, have emerged as promising options for improving outcomes and patient recovery in EC management. Objective:This study aims to evaluate the clinical utility of robot-assisted minimally invasive esophagectomy (RAMIE) in the treatment of EC. Methods:A total of 160 EC patients undergoing treatment at our hospital were included in this study. Patients were randomly assigned to either the research group, receiving RAMIE, or the control group, undergoing thoracoscopic minimally invasive esophagectomy (MIE). Surgical outcomes, postoperative recovery, complication rates, and changes in inflammatory factors (IFs) such as malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were compared between the two groups. Additionally, prognostic survival and EC recurrence rates were assessed at a 1-year follow-up. Results:The research group demonstrated longer operative times, a higher number of dissected lymph nodes, reduced intraoperative bleeding, and quicker postoperative recovery compared to the control group, with significantly fewer complications (P < .05). Furthermore, the research group exhibited lower levels of postoperative IFs and MDA, along with higher levels of SOD and GSH-Px, compared to the control group (P < .05). There was no significant difference between the two groups in terms of prognostic survival and EC recurrence rates (P > .05). Conclusion:RAMIE demonstrates superior efficacy in enhancing therapeutic outcomes and accelerating postoperative recovery in patients with EC, thus establishing its value in EC treatment protocols. RAMIE is suggested as a valuable therapeutic option and warrants clinical adoption for EC management.

The mortality rate of oesophageal squamous cell carcinoma (ESCC) remains high, and conventional TNM systems cannot accurately predict its prognosis, thus necessitating a predictive model. In this study, a 17-gene prognosis-related gene signature (PRS) predictive model was constructed using the random survival forest algorithm as the optimal algorithm among 99 machine-learning algorithm combinations based on data from 260 patients obtained from TCGA and GEO. The PRS model consistently outperformed other clinicopathological features and previously published signatures with superior prognostic accuracy, as evidenced by the receiver operating characteristic curve, C-index and decision curve analysis in both training and validation cohorts. In the Cox regression analysis, PRS score was an independent adverse prognostic factor. The 17 genes of PRS were predominantly expressed in malignant cells by single-cell RNA-seq analysis via the TISCH2 database. They were involved in immunological and metabolic pathways according to GSEA and GSVA. The high-risk group exhibited increased immune cell infiltration based on seven immunological algorithms, accompanied by a complex immune function status and elevated immune factor expression. Overall, the PRS model can serve as an excellent tool for overall survival prediction in ESCC and may facilitate individualized treatment strategies and predction of immunotherapy for patients with ESCC.

Abstract Objectives Immune checkpoint inhibitor (ICI)‐associated myocarditis, particularly severe ICI‐associated myocarditis, has a high mortality rate. However, the predictive value of electrocardiogram (ECG) remains unclear. The present study aimed to evaluate the predictive value of clinical and electrocardiographic parameters for severe myocarditis. Methods Clinical and electrocardiographic data of 73 cancer patients with ICI‐associated myocarditis were retrospectively collected. The severity of ICI‐associated myocarditis was graded using the NCCN guidelines for managing immunotherapy‐related toxicities. Myocarditis grades 1–2 and grades 3–4 were classified as mild and severe myocarditis, respectively. Logistic regression analysis was performed to analyze the predictive value of each parameter in predicting severe myocarditis. Results Among the 73 patients with myocarditis, 20 (27.4%) patients had severe myocarditis. Compared with mild myocarditis group, sinus tachycardia (p = 0.001), QRS duration ≥110 ms (p = 0.001), prolonged QTc interval (p < 0.001), and bundle branch block (p = 0.007) at the time of myocarditis were more common in the severe myocarditis group. Logistic regression analysis revealed that sinus tachycardia (p = 0.028) and QTc interval prolongation (p = 0.007) were predictors of severe myocarditis. Whereas the predictive value of other electrocardiographic parameters was weak. Concurrent targeted therapy didn't increase the risk of severe myocarditis. A high NT‐proBNP level was associated with severe myocarditis. Conclusions ECG at the onset of myocarditis manifested as sinus tachycardia and prolonged QTc interval predicted a high risk of severe myocarditis. Early detection of ECG abnormalities may faciliate early detection of severe ICI‐associated myocarditis.

BACKGROUND:Neoadjuvant immunotherapy, targeting the PD-1 or PD-L1, combined with chemotherapy (NICT), can improve the radical resection and survival rates for locally advanced EC. However, it may impair pulmonary function, and the effect of NICT on pulmonary function and postoperative pulmonary complications in EC patients remains unknown. This study aimed to investigate whether NICT can affect pulmonary functions and postoperative pulmonary complications in EC patients. METHODS:The study retrospectively recruited 220 EC patients who received NICT at the Department of Esophageal Cancer in Tianjin Medical University Cancer Institute & Hospital from January 2021 to June 2022. Changes in pulmonary function before and after NICT were compared. Logistic regression analysis was performed to analyze the correlations of pulmonary functions and clinical characteristics with postoperative pulmonary complications, respectively. RESULTS:The FEV1% pred, FVC, FVC% pred, and FEV1/FVC% significantly increased after NICT, with a P-value of 0.018, 0.005, 0.001, and 0.036, respectively. In contrast, there was a significant decline in the DLCO (8.92 ± 2.34 L before NICT vs. 7.79 ± 2.30 L after NICT; P < 0.05) and DLCO% pred (102.97 ± 26.22% before NICT vs. 90.18 ± 25.04% after NICT; P < 0.05). High DLCO and DLCO% pred at baseline levels were risk factors for DLCO reduction in EC patients after NICT. Advanced age, smoking history, FEV1% pred after NICT, and FVC% pred baseline and after therapy were risk factors for postoperative pulmonary complications, with a P-value of 0.043, 0.038, 0.048, 0.034, and 0.004, respectively. Although the DLCO level decreased after NICT, it did not increase the incidence of postoperative pulmonary complications. CONCLUSION:NICT may improve pulmonary ventilation function but also lead to a decrease in DLCO and DLCO% pred in EC patients. Nevertheless, the decreased DLCO after NICT did not increase the risk of postoperative pulmonary complications.

The average five-year survival rate for esophageal cancer, a common malignant tumor of the digestive system, is barely 20%. The majority of esophageal squamous cell carcinoma (ESCC) patients had already progressed to a locally advanced or even advanced stage at initial diagnosis, making routine surgery ineffective. Chemotherapy and immunotherapy are important neoadjuvant treatments for ESCC, however, it remains unknown how treatment will affect the immunological microenvironment, especially at the spatial level. Here, we presented the TME characters of ESCC from the temporal and spatial dimensions using scRNA-seq and ST, investigated the changes of immune cell clusters in the TME under neoadjuvant chemotherapy and preoperative immunotherapy, and explored the potential mechanisms. It was found that compared with chemotherapy, immunotherapy combined with chemotherapy increased the level of T cell proliferation, partially restored the function of exhausted T cells, induced the expansion of specific exhausted CD8 T cells, increased the production of dendritic cells (DCs), and supported the immune hot microenvironment of the tumor. We also found that CD52 and ID3 have potential as biomarkers of ESCC. Particularly, CD52 may be served as a predictor of the efficacy to screen the advantaged population of different regimens. Through multiple pathways, CAF2 and CAF5's antigen-presenting role affected the other fibroblast clusters, resulting in malignant transformation. We analyzed the immune microenvironment differences between the two regimens to provide a more thorough description of the ESCC microenvironment profile and serve as a foundation for customized neoadjuvant treatment of ESCC.

4048 Background: This study (NCT05476380) aimed to evaluate the safety and efficacy of neoadjuvant camrelizumab plus chemotherapy in patients with locally advanced ESCC, and to explore the potential risk factors of tumor immune microenvironment (TIM) which affect the efficiency of immunotherapy. Methods: Patients with resectable locally advanced thoracic ESCC, staged as T1b-4a, N2-3 (≥3 stations), and M0 or M1 lymph node metastasis (confined to supraclavicular lymph nodes) were enrolled. Eligible patients received intravenous camrelizumab (200 mg, day 2) plus paclitaxel (175 mg/m 2 , day 1) and cisplatin (75 mg/m 2 , day 1) for three 21-day cycles before surgery. The primary endpoint was major pathological response (MPR), defined as ≤10% residual viable tumor cells in resected tissue. In order to screen out the potential biomarkers, the dissected lymph nodes were collected in the pathological complete response (pCR) and non-pCR groups. The infiltrated immune cells and the status of PD-L1 was evaluated by flowcytometry. Results: From February 20, 2021 to July 7, 2022, 38 patients were enrolled. 34 (89.5%) patients completed the full three-cycle treatment successfully. 34 patients underwent surgery and all received R0 resection. The MPR and pCR rates were 67.6% (23/34) and 17.6% (6/34), respectively. There were 2 (5.9%) patients having complete response of the primary tumor but residual disease in lymph nodes alone (ypT0N+). 32 (94.1%) patients had any-grade treatment-related adverse events, with the most common being leukocytopenia (73.5%). 18 (52.9%) patients had adverse events of grade 3 or worse. No treatment-related deaths occurred. Based on our findings, positive lymph nodes were one of the important reasons that the patients could not achieved pCR. TIM of the lymph nodes were then tested. Compared with MPR group, the infiltrated lymphocyte cells in the non-MPR group decreased from 93% to 52.4% (p = 0.02), the infiltrated CD8 + T cells also decreased from 11.8% to 5.9% (p = 0.02). However, the CD4 + T cells showed no significant difference between the MPR and non-MPR groups (46.2% vs 55%, p = 0.27). The expression of PD-L1 in the immune cells is one of the biomarkers for checkpoint inhibitors. In this trial, the expression of PD-L1 in the CD8 + T cells showed significant difference between the MPR and non-MPR groups (14.5% vs 6.7%, p = 0.02). Myeloid-derived suppressor cells (MDSCs) are a group of vastly heterogeneous immunosuppressive cells derived from immature myeloid progenitors that have been linked to poor patient prognosis and immunosuppression. We found more infiltrations of MDSCs in the non-MPR group compared with the MPR group (9.7% vs 4.7%, p = 0.04). Conclusions: Neoadjuvant camrelizumab combined with chemotherapy shows promising efficacy and good safety in ESCC patients. Poor response to immunotherapy was related to lymph node metastasis in the TIM. Clinical trial information: NCT05476380 .

Abstract Background Esophageal squamous cell carcinoma (ESCC) has a dismal prognosis, and hypoxia plays a key role in metastasis and proliferation of ESCC. Thus, we aimed to develop a hypoxia‐based gene signature to assist in the treatment decisions and prognosis. Methods We performed consensus clustering analysis on samples from GSE53625 dataset from the Gene Expression Omnibus (GEO) database and used weighted gene co‐expression network analysis to filter out candidate modules, which were then intersected with differentially expressed genes from clustered subgroups to obtain hypoxia‐related genes (HRGs). After that, the aforementioned genes were used to construct risk score models and validated in The Cancer Genome Atlas (TCGA) database and Cox regression analysis were used to construct a nomogram. Immunohistochemical was used to detect protein expression levels of relevant genes. Moreover, the relationship between risk scores and tumor microenvironment was explored. Results A hypoxia risk model containing six genes (PNPLA1, CARD18, IL‐18, SLC37A2, ADAMTS18, and FAM83C) was constructed by screening key HRGs. Poorer prognosis in the high‐risk group than in the low‐risk group. And Cox regression analysis showed that risk score was an independent prognostic factor. The nomogram based on risk scores could well predict 1‐, 3‐, and 5‐year survival. P53, Wnt, and hypoxia signaling pathways may be some regulatory mechanisms of hypoxia associated with the tumor microenvironment. In addition, we confirmed the high expression of BGN and low expression of IL‐18 in ESCC tissues. Conclusions Our study determined the prognostic value of a 6‐hypoxia gene signature and a prognostic model, providing potential prognostic predictors and therapeutic targets for ESCC.

Abstract Background PTPRF interacting protein alpha 1 (PPFIA1) is reportedly related to the occurrence and progression of several kinds of malignancies. However, its role in esophageal squamous cell carcinoma (ESCC) is unclear. This current study investigated the prognostic significance and biological functions of PPFIA1 in ESCC. Methods Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), and Gene Expression Omnibus (GEO) were used to investigate PPFIA1 expression in esophageal cancer. The relationship between PPFIA1 expression and clinicopathological characteristics and patient survival was evaluated in GSE53625 dataset, and verified in the cDNA array based on qRT–PCR and tissue microarray (TMA) dataset based on immunohistochemistry. The impact of PPFIA1 on the migration and invasion of cancer cells were investigated by wound-healing and transwell assays, respectively. Results The expression of PPFIA1 was obviously increased in ESCC tissues versus adjacent esophageal tissues according to online database analyses (all P < 0.05). High PPFIA1 expression was closely related to several clinicopathological characteristics, including tumor location, histological grade, tumor invasion depth, lymph node metastasis, and tumor-node-metastasis (TNM) stage. High PPFIA1 expression was related to worse outcomes and was identified as an independent prognostic factor of overall survival in ESCC patients (GSE53625 dataset, P = 0.019; cDNA array dataset, P < 0.001; TMA dataset, P = 0.039). Downregulation of PPFIA1 expression can significantly reduce the migration and invasion ability of ESCC cells. Conclusion PPFIA1 is related to the migration and invasion of ESCC cells, and can be used as a potential biomarker to evaluate the prognosis of ESCC patients.

Ubiquitin-specific protease 4 (USP4) represents a potential oncogene involved in various human cancers. Nevertheless, the biological roles and precise mechanism of USP4 in esophageal squamous cell carcinoma (ESCC) progression are not understood. Here, USP4 expression was found to be markedly upregulated in ESCC tumor tissues and cells. Loss- and gain-of-function assays suggested that USP4 silencing inhibited ESCC cell proliferation, migration, and invasion, while USP4 overexpression promoted these behaviors. Consistently, USP4 silencing repressed tumor growth and metastasis in an ESCC nude mouse model in vivo. As a target molecule of USP4, transforming growth factor-β-activated kinase 1 (TAK1) also showed high expression in ESCC. Moreover, we observed that USP4 specifically interacted with TAK1 and stabilized TAK1 protein levels via deubiquitination in ESCC cells. Importantly, USP4 promotes ESCC proliferation, migration, and invasion via the MEK/ERK signaling pathway and can be inhibited by U0126. Neutral red (NR), an inhibitor of USP4 can suppress ESCC progression in vitro and in vivo. Overall, this study revealed that USP4/TAK1 plays crucial roles in ESCC progression by modulating proliferation, migration, and invasion, and USP4 might be a potential therapeutic target in ESCC.

Esophageal carcinoma (EC) is a common malignant tumor of the upper digestive tract worldwide. An analysis of the latest data from cancer centers in China showed that the incidence of EC and the number of deaths due to EC in China in 2015 were 266,000 and 188,000, respectively, ranking sixth (6.3%) and fourth (8.0%) among all malignant tumors. The early diagnosis and treatment of EC and standardized diagnosis and treatment are important tasks for EC healthcare professionals in various centers across the country. At present, the 8th edition of the EC staging system jointly released by Union for International Cancer Control (UICC) and American Joint Committee on Cancer (AJCC) is the most recent, authoritative and widely used EC staging standard. The EC professional committee of the Chinese Anti-Cancer Association also organizes the "EC Standardization Campaign in China" every year to promote the development of EC diagnostic and treatment norms throughout the country. Since 2011, the EC Committee of the Chinese Anti-Cancer Association has published the Guidelines for Standardized Diagnosis and Treatment of EC. Considering the increasing number of EC clinical studies and the continuous progress in diagnostic and treatment technologies in recent years, the updated Guidelines will include the latest progress in the diagnosis and treatment of EC, with a goal of promoting the forward development of EC diagnosis and treatment in clinical practice.

1 病例介绍 患者男性,37岁,主因"突发头痛、头晕2?d,意识障碍5?h"于2021年5月26日在当地医院就诊.该患者就诊前两天,无明显诱因出现持续性头痛、头晕,伴恶心、喷射性呕吐,呕吐物为胃内容物,无肢体无力及麻木症状,在家中观察逐渐加重,就诊当日中午出现意识障碍,表现为问话不答,偶有遵嘱动作.2021年5月26日15:10急去当地医院就诊,于15:15头颅CT检查结果示小脑梗死(左侧为主)合并脑积水(图1);并行血常规、凝血四项、生化等检查,结果基本正常.因患者病情危重,于当日17:03由120救护车向兴安盟人民医院转运.本院卒中中心在获得抢救通知后,17:15派出第五代移动通信技术移动卒中单元(5th generation mobile communication technology mobile stroke unit,5G MSU)进行对接.5G MSU救治小组人员由卒中中心医师和护士、麻醉科医师、急诊科护士及120车队司机组成.历时2?h车程后,于19:055G MSU与患者乘坐救护车在约全部路程的中点位置进行对接.

C-X-C motif chemokine receptor 4 (CXCR4) belongs to the CXC chemokine receptor family, which mediates the metastasis of tumor cells and promotes the malignant development of cancers. However, its biological role and regulatory mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we found that CXCR4 expression was associated with lymph node metastasis and a poor prognosis. In vitro and in vivo studies demonstrated that CXCR4 overexpression promoted ESCC cell proliferation, migration, invasion, and survival, whereas silencing CXCR4 induced the opposite effects. Mechanically, HIF-1α transcriptionally regulates CXCR4 expression by binding to a hypoxia response element in its promoter. HIF-1α-induced ESCC cell migration and invasion were reversed by CXCR4 knockdown or treatment with MSX-122, a CXCR4 antagonist. Collectively, these data revealed that the HIF-1α/CXCR4 axis plays key roles in ESCC growth and metastasis and indicated CXCR4 as a potential target for ESCC treatment.

Background The tumor microenvironment plays an important role in the occurrence and development of tumors. However, there are gaps in understanding the molecular and cellular interactions between tumor cells and the immune tumor microenvironment (TME). The aim of this study was to identify a novel gene that played an important role in the tumor microenvironment of lung adenocarcinoma (LUAD). Methods The gene expression profile and clinical data for LUAD were downloaded from TCGA database. First, we used the ESTIMATE algorithm to evaluate the immune and stromal scores accordingly. Also, we analyzed differentially expressed immune-related genes (IRGs) in the high and low immune/stromal score groups. Then, we used the protein–protein interaction network (PPI network) and a univariate Cox regression analysis to identify the hub gene. After that, we analyzed the relationship between CSF2RB expression and TNM stage/prognosis. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathway regulated by CSF2RB and the Pearson correlation analysis method was used to analyze the correlation between the CSF2RB and immune cells. Finally, we used Western blot, real-time quantitative PCR (RT-qPCR), and immunohistochemistry (IHC) to validate CSF2RB expression in cancer and para-cancerous tissues. Results We identified that CSF2RB played an important role in the tumor microenvironment of LUAD. The expression of CSF2RB in tumor tissues was lower than that in normal tissues. Furthermore, the Kaplan–Meier plotter showed that a low CSF2RB expression was associated with poor survival and multivariate COX regression analysis revealed that the CSF2RB gene was an independent risk factor for prognosis, independent of whether patients received chemotherapy or radiotherapy. More importantly, a high expression of CSF2RB was related to early T, N, and clinical stages. GSEA analysis revealed that CSF2RB associated with diverse immune-related pathways, including T-cell receptor signaling pathway, Toll-like receptor signaling pathway, and B-cell receptor signaling pathway. CSF2RB expression levels were also positively related with the levels of infiltrating CD4+ T cells, macrophages, NK cells, and monocytes in LUAD. Finally, tumor tissues from LUAD patients were used for the assessment of CSF2RB expression. It was significantly lower in tumor sites than in adjacent normal tissues, which was consistent with data analysis. Conclusion CSF2RB effectively predicted the prognosis of patients with lung adenocarcinoma which could also be a potential target for cancer treatment and prevention. However, further studies are required to elucidate the function and regulatory mechanisms of CSF2RB and to develop some novel treatment strategies.

Abstract Background Patients with esophageal squamous cell carcinoma (ESCC) with lymph node metastasis may be misclassified as pN0 due to an insufficient number of lymph nodes examined (LNE). The purpose of this study was to confirm that patients with ESCC are indeed pN0 and to propose an adequate number for the correct nodal stage using the nodal staging score (NSS) developed by the beta‐binomial model. Methods A total of 1249 patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2017, and 1404 patients diagnosed with ESCC in our database between 2005 and 2018 were included. The NSS was developed to assess the probability of pN0 status based on both databases. The effectiveness of NSS was verified using survival analysis, including Kaplan–Meier curves and Cox models. Results Many patients were misclassified as pN0 based on our algorithm due to insufficient LNE. As the number of LNE increased, false‐negative findings dropped; accordingly, the NSS increased. In addition, NSS was an independent prognostic indicator for pN0 in patients with ESCC in the SEER database (hazard ratio [HR] 0.182, 95% confidence interval [CI] 0.046–0.730, p = 0.016) and our database (HR 0.215, 95% CI 0.055–0.842, p = 0.027). A certain number of nodes must be examined to achieve 90% of the NSS. Conclusions NSS could determine the probability of true pN0 status for patients, and it was sufficient in predicting survival and obtaining adequate numbers for lymphadenectomy.

Background Synchronous multiple primary esophageal squamous cell carcinoma (S-MPESCC) refers to more than one primary esophageal carcinoma detected in a solitary patient at the time of initial presentation. The purpose of this study was to evaluate the clinicopathological features, appropriate surgical approaches and long-term survival in patients with S-MPESCC by comparing with those with solitary esophageal squamous cell carcinoma (SESCC). Methods In total, 567 patients with esophageal squamous cell carcinoma surgically resected in Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2018 were screened for retrospective analysis (50 in the S-MPESCC group and 516 in the SESCC group). Results No significant difference was observed in terms of other characteristics except total alcohol consumption ( P = 0.029). S-MPESCC had higher lymph node rate than SESCC (62.0% and 44.1%, respectively; P = 0.015) especially in upper mediastinal (32.0% and 18.6%, respectively; P = 0.023) and abdominal (38.0% and 22.8%, respectively; P = 0.017) regions. The survival was not different between the two groups, and the 5-year survival rates of S-MPESCC and SESCC were 46.2% and 50.8%, respectively ( P = 0.507). But for patients with pT3-4 cancers, the survival in S-MPESCC was worse than that in SESCC ( P = 0.033). In the multivariate analysis, pT stage of primary cancer was an important independent predictor of prognosis in patients with S-MPESCC (hazard ratio [HR], 3.968; 95% confidence interval [CI], 1.031 to 15.268; P = 0.045). Conclusions S-MPESCC was significantly different from SESCC in terms of clinicopathological characteristics include alcohol intake and pattern of lymphatic metastasis. Furthermore, S-MPESCC showed worse long-term survival than SESCC with increasing depth of primary cancer infiltration.

Obesity is closely related to a poor prognosis in patients with advanced colorectal cancer (CRC), but the mechanisms remain unclear. Ferroptosis is a form of nonapoptotic cell death characterized by lipid reactive oxygen species (ROS) accumulation and iron dependency and is associated with the chemoresistance of tumors. Here, it is shown that adipose-derived exosomes reduce ferroptosis susceptibility in CRC, thus promoting chemoresistance to oxaliplatin. It is found that microsomal triglyceride transfer protein (MTTP) expression is increased in the plasma exosomes of CRC patients with a high body fat ratio, serving as an inhibitor of ferroptosis and reducing sensitivity to chemotherapy. Mechanistically, the MTTP/proline-rich acidic protein 1 (PRAP1) complex inhibited zinc finger E-box binding homeobox 1 expression and upregulated glutathione peroxidase 4 and xCT, leading to a decreased polyunsaturated fatty acids ratio and lipid ROS levels. Moreover, experiments are carried out in organoids, and a tumor implantation model is established in obese mice, demonstrating that the inhibition of MTTP increases the sensitivity to chemotherapy. The results reveal a novel intracellular signaling pathway mediated by adipose-derived exosomes and suggest that treatments targeting secreted MTTP might reverse oxaliplatin resistance in CRC.

We aimed to investigate the expression and clinical value of PTPRF interacting protein alpha 1 (PPFIA1) in esophageal squamous cell carcinoma (ESCC). The Oncomine, GEPIA, and GEO databases were utilized to explore PPFIA1 mRNA expression in esophageal cancer. The associations of PPFIA1 expression with clinicopathological variables and prognosis were evaluated in the GSE53625 dataset and verified in qRT-PCR-based cDNA array and immunohistochemistry-based tissue microarray (TMA) datasets. The interactions between PPFIA1 and other genes based on the protein-protein interaction (PPI) network was analyzed via the STRING website. We found PPFIA1 expression was obviously upregulated in ESCC tissues versus adjacent normal tissues according to online database analyses (P<0.05). High PPFIA1 expression was significantly associated with several clinicopathological features, including tumor size, histological grade, tumor invasion depth, lymph node metastasis, and TNM stage. High PPFIA1 expression was related to worse outcomes and was identified as an independent prognostic indicator of overall survival in ESCC patients (GSE53625 dataset, P=0.004; cDNA array dataset, P<0.001; TMA dataset, P=0.039). PPI analysis demonstrated that PPFIA1 was highly correlated with multiple genes, including UNC13B, RAB3A, PTPRD, and SYT1. In conclusion, PPFIA1 may be associated with ESCC progression and could be used as a biomarker for prognostic evaluation in ESCC patients.