Colorectal cancer (CRC) is the leading cause of cancer-related morbidity and mortality globally. Despite the established link between mitochondrial dysfunction and various cancers, including CRC, the precise role of mitochondrial genes remains unclear. This study aimed to elucidate the influence of mitochondrial-related genes on CRC through a multi-omics approach. The MitoCarta3.0 database, methylation quantitative trait loci (mQTL), expression QTL (eQTL), and protein QTL (pQTL) data from multiple sources were utilized. CRC-related genetic data were obtained from the IEU OpenGWAS project and FinnGen database. The MR analysis employed five regression models. Integration of the results from three levels of gene regulation revealed significant associations between mitochondrial-related gene regulation and CRC. We identified 21 genes that exhibit multi-omics evidence associated with CRC. Tier 1 gene PNKD showed significant associations with CRC across multiple omics levels. Tier 2 genes, RBFA, COX15, TXN2, and ACSF3, were linked to CRC at the mQTL-eQTL level. Sixteen tier 3 genes were also identified. A total of eight genes, including COX15, had been identified as potential therapeutic and drug targets. A total of eight genes, including COX15, had been identified as potential drug targets. Additionally, the final structures of the corresponding eight proteins and their respective drugs had been successfully determined. The multi-omics approach identified several mitochondrial-related genes significantly associated with CRC risk, providing new insights into the role of mitochondrial dysfunction in CRC pathogenesis, and potentially providing further investigation and future therapeutic strategies targeting mitochondrial pathways in CRC management.

Background Gastric cancer (GC) is the fifth most common cancer and the third most common cause of cancer death worldwide. Plant homeodomain (PHD)-finger domain protein PHF5A has been demonstrated to play a promoting role in a variety of cancers. This study aimed to clarify the role of PHF5A in the progression of GC and its potential mechanism of action. Methods Immunohistochemical staining experiments were performed based on tissues from clinical GC patients to reveal PHF5A expression. A series of functional experiments in vitro and in vivo were used to clarify the role of PHF5A in GC. Results Clinically, PHF5A was abundantly expressed in GC and existed clinical value indicating poor prognosis. In addition, GC cells with knockdown of PHF5A expression showed slowed proliferation, enhanced sensitivity to apoptosis and inhibition of migration. Mechanically, knockdown of PHF5A led to decreased protein stability of FOS, which was mediated ubiquitination of E3 ubiquitin ligase S-phase kinase-associated protein 2 (SKP2). Moreover, downregulation of FOS attenuated the promotion of PHF5A overexpression on GC cells. Consistently, Pladienolide B (PHF5A inhibitor) treatment reversed the induction of PHF5A overexpression on the malignant phenotypes and tumor formation of GC cells. Conclusion Knockdown of PHF5A inhibited the progression of GC through SKP2-mediated ubiquitination of FOS, which may be a promising candidate target with potential therapeutic value.

Periostin (POSTN) is involved in many biological processes and is associated with the occurrence and development of several cancers, while its role in gastric cancer is not clear. We aimed to demonstrate the relationship between POSTN and gastric cancer based on publicly available data from The Cancer Genome Atlas (TCGA) database. POSTN expression data and corresponding clinical information were downloaded from TCGA database. We compared the expression of POSTN in gastric cancer samples and normal samples. POSTN-related differentially expressed genes (DEGs) were identified for further functional enrichment analysis. In addition, the relationships between POSTN expression and clinicopathological features and survival in patients with gastric cancer were also investigated through univariate and multivariate Cox regression analyses. Furthermore, a nomogram was constructed to predict the survival probability of gastric cancer patients. POSTN expression in gastric cancer was significantly higher than that in normal gastric tissues (p < 0.001). High POSTN expression in gastric cancer was significantly related to poor prognostic features, including greater tumor extent (odds ratio [OR] = 1.638 for T3 and T4 vs. T1 and T2), worse histological type (OR = 0.329 for diffuse type vs. tubular type), and advanced histological grade (OR = 1.646 for grade 3 vs. grades 1 and 2) (all p < 0.05). The 118 identified DEGs were primarily enriched in pathways related to tumorigenesis and tumor progression, including the TGF-β signaling pathway, the WNT signaling pathway, and the signaling by VEGF. POSTN expression was positively correlated with the enrichment of the macrophages (r = 0.599, p < 0.001), helper T2 cells (r = 0.146, p = 0.005), and CD8 + T cells (r = 0.190, p < 0.001), but negatively correlated with the enrichment of Th17 cells (r =  − 0.130, p = 0.012) and NK CD56bright cells. Kaplan–Meier survival analysis showed that high POSTN expression is associated with a short overall survival (hazard ratio [HR] = 1.54; p = 0.011). In the multivariate cox regression analysis, high POSTN expression was confirmed to be an independent predictor of poor overall survival (HR = 1.681; p = 0.017). The constructed nomogram can well predict the 1 and 3 years overall survival probability of patients with GC (0.696 [95% CI, 0.671–0.721]). POSTN plays an important role in the progression and prognosis of gastric cancer, and it may serve as a useful biomarker to predict survival in gastric cancer patients.

BackgroundColon cancer (CC) is the second most common gastrointestinal malignancy. About one in five patients have already developed distant metastases at the time of initial diagnosis, and up to half of patients develop distant metastases from initial local disease, which leads to a poor prognosis for CC patients. Necroptosis plays a key role in promoting tumor growth in different tumors. The purpose of this study was to construct a prognostic model composed of necroptosis-related genes (NRGs) in CC.MethodsThe Cancer Genome Atlas was used to obtain information on clinical features and gene expression. Gene expression differential analysis, weighted gene co-expression network analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator regression algorithm were utilized to identify prognostic NRGs. Thereafter, a risk scoring model was established based on the NRGs. Biological processes and pathways were identified by gene ontology and gene set enrichment analysis (GSEA). Further, protein-protein interaction and ceRNA networks were constructed based on mRNA-miRNA-lncRNA. Finally, the effect of necroptosis related risk score on different degrees of immune cell infiltration was evaluated.ResultsCALB1, CHST13, and SLC4A4 were identified as NRGs of prognostic significance and were used to establish a risk scoring model. The time-dependent receiver operating characteristic curve analysis revealed that the model could well predict the 1-, 3-, and 5-year overall survival (OS). Further, GSEA suggested that the NRGs may participate in biological processes, such as the WNT pathway and JAK-Stat pathway. Eight key hub genes were identified, and a ceRNA regulatory network, which comprised 1 lncRNA, 5 miRNAs and 3 mRNAs, was constructed. Immune infiltration analysis revealed that the low-risk group had significantly higher immune-related scores than the high-risk group. A nomogram of the model was constructed based on the risk score, necroptosis, and the clinicopathological features (age and TNM stage). The calibration curves implied that the model was effective at predicting the 1-, 3-, and 5-year OS of CC.ConclusionOur NRG-based prognostic model can assist in the evaluation of CC prognosis and the identification of therapeutic targets for CC.

There are few reports on disease-specific survival (DSS) prediction systems for resected gastric cancer (GC) patients. The aim of this study was to create a nomogram based on the log odds of the negative lymph node/T stage ratio (LONT) for individual risk prediction. We applied the Surveillance, Epidemiology, and End Results (SEER) Program database released in 2021 to screen GC patients from 2010 to 2015. Using a competitive risk model, we plotted the cumulative risk curve of variables for gastric cancer–specific death and death from other causes at each time point. According to the minimum BIC, we constructed and assessed a nomogram for the 12-month, 36-month, and 60-month cumulative mortality probabilities assessed by time-dependent ROC curves (time-AUCs), the C-index, Brier scores, decision curve analysis (DCA), and calibration curves. A total of 3895 patients were ultimately included and randomly assigned to two sets: the training set (n = 2726, 70%) and the validation set (n = 1169, 30%). The LONT was a remarkable independent predictor of gastric cancer–specific death (high versus low: 0.705, 95% CI 0.524–0.95, p = 0.021). The variables selected based on the minimum BIC were as follows: location, AJCC, AJCC.T, AJCC.N, radiotherapy, LONT.cat, and chemotherapy. According to the time-AUC, C-index, Brier score, DCA, and calibration curves, the nomogram risk score had excellent survival prediction ability for DSS. A low LONT was associated with a high cumulative incidence of DSS. A prognostic nomogram model based on the LONT could effectively predict DSS for resectable GC patients.

Background Colon adenosquamous carcinoma is an extremely rare cancer, especially in young people. No case of colon adenosquamous carcinoma in pediatric patient has been reported so far. Case presentation Here we present the case of a 16-year-old Chinese girl diagnosed with adenosquamous carcinoma of sigmoid colon. We performed laparoscopic sigmoidectomy with lymphadenectomy on the patient. Unfortunately, she developed liver metastasis less than 1 month after surgery. Then we implemented percutaneous radiofrequency ablation of liver mass and 4 cycles of adjuvant chemotherapy on her. However, liver metastasis recurred less than 4 months after radiofrequency ablation. The girl eventurally died in 8 months after surgical resection of sigmoid colon. As far as we know, this girl is the youngest patient with sigmoid colon adenosquamous carcinoma reported so far, and the first reported case of colon adenosquamous carcinoma in pediatrics. Conclusion Only 8 months from detection to death, this case indicates the prognosis of colon adenosquamous carcinoma is poor, and adenosquamous carcinoma of colon may even have worse prognosis in pediatrics than in adults. In addition, cases with liver metastasis have a awfully unfavorable prognosis for colon adenosquamous carcinoma patients.

Double tract reconstruction (DTR) is the main digestive tract reconstruction method after proximal gastrectomy (PG). Single tract jejunal interposition (STJI) derived from the double tract reconstruction is also increasingly used in clinical practice. However, there is still a great controversy as to which of the two reconstruction methods can achieve better results. In this study, we systematically reviewed studies on DTR and STJI after PG and performed a meta-analysis. We searched PubMed, Embase, and Cochrane Library databases for clinical studies comparing DTR and STJI after PG to December 2021 without language restriction. Review Manager (version5.4) software was used to perform meta-analysis on operative outcomes, postoperative complications and nutritional outcomes. The protocol for this meta-analysis was registered with PROSPERO (CRD42022301455). Five randomized controlled trials involving 453 patients were included in the meta-analysis. There were no significant differences between DTR and STJI in terms of intraoperative blood loss, postoperative hospital stay, incidence of reflux esophagitis, anastomotic complications and total complications. The operation time of STJI group was longer than that of DTR group [WMD − 0.79; 95

目的:探讨进展期胃上部癌新辅助化疗(NAC)联合腹腔镜胃癌根治术的可行性.方法:回顾性分析2013年1月至2017年10月在郑州大学附属肿瘤医院接受NAC后行胃癌根治术并D2淋巴清扫的进展期胃上部癌患者193例的临床资料,行腹腔镜手术者76例,行开腹手术者117例;患者均采用SOX或XELOX方案进行NAC.使用倾向性评分匹配法(PSM)对两组进行1:1匹配得到组间协变量均衡的样本,比较两组患者术中情况、术后恢复情况及预后.结果:PSM后,共138例纳入本研究,腹腔镜和开腹组各69例.腹腔镜组较开腹组手术时间长、术后胃肠功能恢复时间快(P<0.05).腹腔镜组和开腹组3 a无复发生存率分别为68.6％、67.1％,3 a总生存率分别为75.8％和77.6％,两组生存曲线比较差异均无统计学意义(P>0.05).结论:NAC联合腹腔镜胃癌根治术治疗进展期胃上部癌安全可行.

Objective: To compare the efficacy between laparoscopic and open proximal gastrectomy with double-tract reconstruction for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) 18 to 80 years old; (2) Siewert II and III AEG was confirmed by preoperative gastroscopy and biopsy, which could not be resected by endoscopy; patients undergoing radical proximal gastrectomy with double-tract reconstruction; (3) contrast-enhanced abdominal CT staging was cT1-2N0M0; (4) Eastern Cooperative Oncology Group (ECOG) physical status score <2 points, American Association of Anesthesiologists (ASA) grade 1 to 2; (5) patients agreed to perform proximal gastrectomy and signed an informed consent. Those who had undergone neoadjuvant radiochemotherapy, suffered from serious mental diseases and had incomplete data were excluded. According to the above criteria, clinical data of 84 consecutive patients with Siewert II and III AEG undergoing surgery at General Surgery Department of The Affiliated Tumor Hospital of Zhengzhou University from October 2010 to December 2018 were collected and analyzed. Of 84 patients, 61 underwent open proximal gastrectomy with double-tract reconstruction (OPG group), while 23 underwent laparoscopic proximal gastrectomy with double-tract reconstruction (LPG group). The perioperative complications and postoperative reflux esophagitis of two groups were compared. A P-value of <0.05 was considered to be statistically significant. Results: Among 84 cases, 74 were male and 10 were female. There were 43 cases of Siewert type II and 41 cases of Siewert type III. There were no significant differences in age, gender, body mass index, comorbidities, Siewert type, and tumor staging between the two groups (all P>0.05). As compared to the OPG group, the LPG group had longer operation duration [(223±21) minutes vs. (161±14) minutes, t=15.352, P<0.001], less intraoperative blood loss [195 (150, 215) ml vs. 208 (192, 230) ml, Z=2.143, P=0.032], and shorter time to flatus [(2.8±0.7) days vs. (3.3±0.9) days, t=2.477, P=0.015]. There were no significant differences in the number of harvested lymph nodes, time to the first meal and postoperative hospital stay between the two groups (all P>0.05). Postoperative complications developed in 2 cases (8.7%, 1 case each for anastomotic leakage and intestinal obstruction) in the LPG group and 5 cases (8.2%, 1 case each for anastomotic leakage, anastomotic bleeding, and anastomotic stenosis, 2 cases of incision infection) in the OPG group (χ(2)=5.603, P=0.231). The median follow-up was 41.2 (12.8-110.5) months. One patient (1.6%,1/61) had obvious reflux symptoms in the OPG group, compared with none in the LPG group (χ(2)=0.644, P=0.422). Esophagitis occurred in 1 case (4.8%, 1/21) in LPG group, compared with 4 patients (7.1%, 4/56) in the OPG group, without significant difference between the two groups (χ(2)=0.505, P=0.477). Conclusion: Laparoscopic proximal gastrectomy with double-tract reconstruction is safe and feasible without increasing the risk of postoperative complication and reflux esophagitis.

Background: To investigate the safety and merits of laparoscopic proximal gastrectomy with double-tract reconstruction (LPG-DT) for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). Methods: Retrospective analysis of the clinical data of 100 consecutive patients with Siewert II and III AEG treated at the Affiliated Tumor Hospital of Zhengzhou University from October 2010 to October 2019 was performed. Out of these patients, 69 underwent open proximal gastrectomy with double-tract reconstruction (OPG-DT), while 31 underwent LPG-DT. The clinicopathological characteristics, perioperative data, and short-term outcomes of the two groups were compared. A P value <0.05 was considered statistically significant. Results: Males accounted for 87% of all patients. Lymph nodes (LNs) count, time to first meal, postoperative length of stay, and postoperative complications were similar between the OPG-DT and LPG DT group. flatus time was significantly shorter in the LPG-DT group (P<0.05), while the duration of operation was significantly shorter in the the OPG-DT group (P<0.001). Furthermore, the LPG-DT group has less blood loss, shorter flatus time, and lower postoperative-day-5 white blood cell (WBC) count and C-reactive protein (CRP) levels (P<0.05). Conclusions: Although LPG-DT took longer to perform, its advantages of reduced blood loss and less surgical stress reflected on inflammatory markers supports an acceptable surgical option for Siewert II and III AEG.

Introduction Gallbladder cancer (GBC), the sixth most common gastrointestinal tract cancer, poses a significant disease burden in China. However, no national representative data are available on the clinical characteristics, treatment and prognosis of GBC in the Chinese population.Methods and analysis The Chinese Research Group of Gallbladder Cancer (CRGGC) study is a multicentre retrospective registry cohort study. Clinically diagnosed patient with GBC will be identified from 1 January 2008 to December, 2019, by reviewing the electronic medical records from 76 tertiary and secondary hospitals across 28 provinces in China. Patients with pathological and radiological diagnoses of malignancy, including cancer in situ, from the gallbladder and cystic duct are eligible, according to the National Comprehensive Cancer Network 2019 guidelines. Patients will be excluded if GBC is the secondary diagnosis in the discharge summary. The demographic characteristics, medical history, physical examination results, surgery information, pathological data, laboratory examination results and radiology reports will be collected in a standardised case report form. By May 2021, approximately 6000 patient with GBC will be included. The clinical follow-up data will be updated until 5 years after the last admission for GBC of each patient. The study aimed (1) to depict the clinical characteristics, including demographics, pathology, treatment and prognosis of patient with GBC in China; (2) to evaluate the adherence to clinical guidelines of GBC and (3) to improve clinical practice for diagnosing and treating GBC and provide references for policy-makers.Ethics and dissemination The protocol of the CRGGC has been approved by the Committee for Ethics of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (SHEC-C-2019–085). All results of this study will be published in peer-reviewed journals and presented at relevant conferences.Trial registration number NCT04140552, Pre-results.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.

目的:探讨ypTNM分期联合肿瘤退缩分级(tumor regression grade,TRG)将当前系统进一步划分和扩展,评估不同亚组患者预后.方法:回顾性分析2012年1月至2016年2月在郑州大学附属肿瘤医院接受新辅助化疗后行手术治疗的局部进展期胃癌患者的临床资料.根据AJCC第8版ypTNM分期以及AJCC-TRG标准对术后组织标本重新评价.根据患者新辅助化疗术后ypTNM分期联合TRG,将该系统分为9个不同亚组.采用Kaplan-Meier生存曲线计算ypTNM各分期联合AJCC-TRG评估相同分期患者的3年、5年总生存(overall survival,OS)率以及中位生存时间(median overall survival,mOS),并根据结果将ypTNM各分期系统进一步划分和扩展,筛选出预后最差亚组患者.结果:共纳入424例患者,其中男性330例,女性94例,中位年龄60岁.中位生存时间为40个月.相同ypTNM分期不同TRG亚组,Kaplan-Meier生存分析结果显示:ypTNM Ⅰ期:TRG1与TRG2患者OS(P=0.715)之间的差异无统计学意义,TRG1与TRG3患者OS(P=0.001)以及TRG2与TRG3患者OS(P=0.001)之间的差异均具有统计学意义,且TRG3组预后最差(mOS为23个月);ypTNMⅡ期:TRG1与TRG2患者OS(P=0.105)之间的差异无统计学意义,TRG1与TRG3患者OS (P＜0.001)以及TRG2与TRG3患者OS (P=0.006)之间的差异均具有统计学意义,且TRG3组预后最差(3个亚组mOS分别为79、52和35个月);ypTNMⅢ期:TRG1与TRG2患者OS (P=0.001)、TRG1与TRG3患者OS (P＜0.001)以及TRG2与TRG3患者OS (P＜0.001)之间的差异均具有统计学意义,且TRG3组预后最差(3个亚组mOS分别为51、23、15个月).结论:ypTNM分期联合AJCC-TRG分级可将相同分期患者进一步划分和扩展,并筛选出预后最差亚组患者,有助于临床医生判断患者病情,给予个体化治疗.

Numerous studies have shown that long uncoded RNA (lncRNA) MSC-AS1 may play an important role in the occurrence and development of some types of cancer. However, its role in gastric cancer has rarely been discussed. This study aimed to clarify the association between lncRNA MSC-AS1 and gastric cancer using The Cancer Genome Atlas (TCGA) database. We determined the expression of MSC-AS1 using the Wilcoxon rank sum test; in addition, logistic regression was applied to evaluate the association between MSC-AS1 and clinicopathological characteristics. Also, Kaplan-Meier and Cox regression were used to evaluate the relationship between MSC-AS1 and survival. A nomogram was conducted to predict the impact of MSC-AS1 on prognosis. Moreover, Gene Set enrichment analysis (GSEA) was performed to annotate the biological function of MSC-AS1. Quantitative analysis of immune infiltration was carried out by single-set GSEA (ssGSEA). The MSC-AS1 level was elevated in gastric cancer tissues. An increased MSC-AS1 level was significantly correlated with T stage (odds ratio [OR] = 2.55 for T3 and T4 vs. T1 and T2), histological type (OR = 5.28 for diffuse type vs. tubular type), histological grade (OR = 3.09 for grade 3 vs. grades 1 and 2), TP53 status (OR = 0.55 for mutated vs. wild type), and PIK3CA status (OR = 0.55 for mutated vs. wild type) (all p < 0.05) by univariate logistic regression. Kaplan-Meier survival analysis showed high MSC-AS1 expression had a poor overall survival [hazard ratio (HR) = 1.75; 95% confidence interval (CI): 1.25–2.45; p = 0.001] and progression-free interval (HR = 1.47; 95% CI: 1.03–2.10; p = 0.034). Multivariate survival analysis revealed that MSC-AS1 expression (HR = 1.681; 95% CI: 1.057–2.673; p = 0.028) was independently correlated with overall survival. GSEA demonstrated that the P38/MAPK pathway, the VEGF pathway, the cell adhesion molecules cams, the NOD-like receptor signaling pathway were differentially enriched in the high MSC-AS1 expression phenotype. SsGSEA and Spearman correlation revealed the relationships between MSC-AS1 and macrophages, NK cells, and Tems were the strongest. Coregulatory proteins were included in the PPI network. Upregulated lncRNA MSC-AS1 might be a potential biomarker for the diagnosis and prognosis of gastric cancer.

The incidence of proximal gastric cancer has shown a rising trend in recent years. Surgery is still the main way to cure proximal gastric cancer. Total gastrectomy with D2 lymph node dissection was considered to be the standard procedure for proximal gastric cancer in the past several decades. However, in recent years, many studies have confirmed that proximal gastrectomy can preserve part of the stomach function and can result in a better quality of life of the patient than total gastrectomy. Therefore, proximal gastrectomy is increasingly used in patients with proximal gastric cancer. Unfortunately, there are some concerns after proximal gastrectomy with traditional esophagogastrostomy. For example, the incidence of reflux esophagitis in patients who underwent proximal gastrectomy with traditional esophagogastrostomy is significantly higher than those patients who underwent total gastrectomy. To solve those problems, various functional digestive tract reconstruction methods after proximal gastrectomy have been proposed gradually. In order to provide some help for clinical treatment, in this article, we reviewed relevant literature and new clinical developments to compare various kinds of functional digestive tract reconstruction methods after proximal gastrectomy mainly from perioperative outcomes, postoperative quality of life and survival outcomes aspects. After comparison and discussion, we drew the conclusion that various functional reconstruction methods have their own advantages and disadvantages; large scale high-level clinical studies are needed to choose an ideal reconstruction method in the future. Besides, in clinical practice, surgeons should consider the condition of the patient for individualized selection of the most appropriate reconstruction method.

Long non-coding RNAs (lncRNAs) regulate a series of biological processes, and their anomalous expression exerts critical roles in progression of multiple malignancies, including colorectal cancer (CRC). The present study was designed to provide new ideas and perspectives for the role of lncRNA MCF2L-AS1 and disclose the underlying mechanism in CRC. Herein, we observed that MCF2L-AS1 expression was enriched in CRC tissues and cell lines. Additionally, silencing of MCF2L-AS1 dramatically impeded cell proliferation, invasion and migration capacities of CRC, and distinctly attenuated the expression of invasion associated targets MMP-2 and MMP-9. Moreover, depletion of MCF2L-AS1 apparently restricted the glucose consumption and lactate production, and downregulated GLUT1 and LDHA expression. More importantly, we predicted and verified that MCF2L-AS1 acted as a molecular sponge for miR-874-3p and inversely regulated miR-874-3p expression. Interesting, FOXM1 was identified as direct target of miR-874-3p, and positively modulated by MCF2L-AS1 through sponging miR-874-3p. Mechanistically, MCF2L-AS1 accelerated cell proliferation, invasion and glycolysis through competitively binding to miR-874-3p, leading to enhance FOXM1 expression. Collectively, these outcomes highlighted that MCF2L-AS1 acted as a motivator by modulating the miR-874-3p/FOXM1 axis, thereby aggravating tumorigenesis and glycolysis progress of CRC, disclosing that MCF2L-AS1 may serve as a valuable and promising therapeutic strategy for CRC.

BACKGROUND:Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate.AIM:To investigate whether RL can improve the prognosis of patients with T1b GBC.METHODS:We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China. The log-rank test and Cox proportional hazards model were used to compare the overall survival (OS) of patients who underwent cholecystectomy (Ch) + RL and those who underwent Ch only. To investigate whether combined hepatectomy (Hep) improved OS in T1b patients, we studied patients who underwent Ch + RL to compare the OS of patients who underwent combined Hep and patients who did not.RESULTS:Of the 121 patients (aged 61.9 ± 10.1 years), 77 (63.6%) underwent Ch + RL, and 44 (36.4%) underwent Ch only. Seven (9.1%) patients in the Ch + RL group had lymph node metastasis. The 5-year OS rate was significantly higher in the Ch + RL group than in the Ch group (76.3% vs 56.8%, P = 0.036). Multivariate analysis showed that Ch + RL was significantly associated with improved OS (hazard ratio: 0.51; 95% confidence interval: 0.26-0.99). Among the 77 patients who underwent Ch + RL, no survival improvement was found in patients who underwent combined Hep (5-year OS rate: 79.5% for combined Hep and 76.1% for no Hep; P = 0.50).CONCLUSION:T1b GBC patients who underwent Ch + RL had a better prognosis than those who underwent Ch. Hep + Ch showed no improvement in prognosis in T1b GBC patients. Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines, RL was only performed in 63.6% of T1b GBC patients. Routine Ch + RL should be advised in T1b GBC.

BACKGROUND:Total gastrectomy and proximal gastrectomy (PG) are both surgical options for the treatment of Siewert type III adenocarcinoma of the esophagogastric junction (AEG). Currently there is no consensus on selecting which procedure to perform; in particular, there are few reports of long-term outcomes for patients with local advanced AEG. The aim of this study was to validate the usefulness of PG with double-tract reconstruction in Siewert type III AEG.METHODS:The clinical data of patients with Siewert type III AEG underwent PG with double-tract reconstruction (PG-DT) or total gastrectomy with Roux-en-Y anastomosis (TG-RY) at our hospital between October 2010 and October 2018. According to the defined inclusion and exclusion criteria, 2,146 cases were enrolled in this study. A 1-to-1 propensity score matching (PSM) was performed to compare the short and long-term outcomes between the 2 groups.RESULTS:The operation time was longer in the PG-DT group, and the proportion rates of complications and recovery time was similar in the 2 groups. The rates of maintaining bodyweight and free-fat mass index were significantly higher in patients who underwent PG-DT compared to those who underwent TG-RY. While complications, recovery time and survival are similar between two groups.CONCLUSIONS:Regarding short-term outcomes, PG-DT seemed to be superior in terms of maintaining body weight and skeletal muscle compared to TG-RY, while both had similar complications. It was found that PG-DT enabled a potentially longer survival of pathological stage II and III Siewert type III AEG, although the finding was statistically insignificant. These results may help surgeons to determine the appropriate surgical approach and strategy for patients with early and locally advanced Siewert type III AEG.