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Background: Immunotherapy brings new hope to patients with advanced gastric cancer. However, liver metastases can reduce the efficacy of immunotherapy in patients. Tumor-associated macrophages (TAMs) may be the cause of this reduction in efficacy. SPP1 + TAMs are considered to have immunosuppressive properties. We aimed to investigate the involvement of SPP1 + TAMs in the metastasis of gastric cancer. Methods: The single-cell transcriptome was combined with batched BULK datasets for analysis. Animal models were used to verify the analysis results. Results: We reveal the interaction of SPP1 + TAMs with CD8 + exhausted T cells in metastatic cancer. Among these interactions, GDF15-TGFBR2 may play a key immunosuppressive role. We constructed an LR score to quantify interactions based on ligands and receptors. The LR score is highly correlated with various immune features and clinical molecular subtypes. The LR score may also guide the prediction of the efficacy of immunotherapy and prognosis. Conclusions: The crosstalk between SPP1 + TAMs and CD8 + exhausted T cells plays a key immunosuppressive role in the gastric metastatic cancer microenvironment. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most prevalent and second most lethal cancer globally, with gene mutations and tumor metastasis contributing to its poor prognosis. Single-cell sequencing technology enables high-throughput analysis of the genome, transcriptome, and epigenetic landscapes at the single-cell level. It offers significant insights into analyzing the tumor immune microenvironment, detecting tumor heterogeneity, exploring metastasis mechanisms, and monitoring circulating tumor cells (CTCs). This article provides a brief overview of the technical procedure and data processing involved in single-cell sequencing. It also reviews the current applications of single-cell sequencing in CRC research, aiming to enhance the understanding of intratumoral heterogeneity, CRC development, CTCs, and novel drug targets. By exploring the diverse molecular and clinicopathological characteristics of tumor heterogeneity using single-cell sequencing, valuable insights can be gained into early diagnosis, therapy, and prognosis of CRC. Thus, this review serves as a valuable resource for identifying prognostic markers, discovering new therapeutic targets, and advancing personalized therapy in CRC. [ABSTRACT FROM AUTHOR]

Protein lysine acetylation affects colorectal cancer (CRC) distant metastasis through multiple pathways. In a previous proteomics screen, we found that isocitrate dehydrogenase 1 (IDH1) is hyperacetylated in CRC primary tumors and liver metastases. Here, we further investigate the function of IDH1 hyperacetylation at lysine 224 in CRC progression. We find that IDH1 K224 deacetylation promotes its enzymatic activity and the production of α‐KG, and we identify sirtuin‐2 (SIRT2) as a major deacetylase for IDH1. SIRT2 overexpression significantly inhibits CRC cell proliferation, migration, and invasion. IDH1 acetylation is modulated in response to intracellular metabolite concentration and regulates cellular redox hemostasis. Moreover, IDH1 acetylation reversely regulates HIF1α‐dependent SRC transcription which in turn controls CRC progression. Physiologically, our data indicate that IDH1 deacetylation represses CRC cell invasion and migration in vitro and in vivo, while the hyperacetylation of IDH1 on K224 is significantly correlated to distant metastasis and poor survival of colorectal cancer patients. In summary, our study uncovers a novel mechanism through which SIRT2‐dependent IDH1 deacetylation regulates cellular metabolism and inhibits liver metastasis of colorectal cancer. Synopsis: SIRT2 inhibits colorectal cancer cell invasion and metastasis by regulating IDH1 acetylation on K224. SIRT2 deacetylates IDH1 on Lys224 in colorectal cancer.IDH1 K224 acetylation activates HIF1α/SRC axis to promote colorectal cancer metastasis.IDH1 acetylation predicts poor prognosis in colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Staging laparoscopy(SL) is a recommended technique for the staging of Gastric Cancer(GC) and provides the indication for a radical surgery. Considering the medical practice in China, the standardized and regular usage of SL is yet to be spread. However, existing guidelines vary and make an ambiguity of indication for SL. Besides, the specific indication for Chinese patients remains a niche. This study aims to the essential, missing information of Chinese patients and tries to normalize the indication of LS in medical practice in China.Methods: The study is a prospective, multicenter cohort study being conducted in China with a total of 450 patients, all diagnosed with locally advanced gastric cancer (cT2-4 N0-3 M0, no evidence of intra-abdominal dissemination) through Computed Tomography(CT) and/or Endoscopic Ultrasonography(EUS). Peritoneal lavage is regularly performed during the SL. Multivariate Cox regression model and receiver-operator characteristic(ROC) analysis will be used to analyze the significant risk factors of intra-abdominal metastasis(including peritoneal dissemination and a positive cytological result).Discussion: This confirmatory study will provide us with the specific positive rate of intraabdominal metastasis of GC in China, compared with empirical evidence of 20%. We expect this trial will contribute to our discovery of the specific risk factors of intra-abdominal metastasis of Chinese patients and to the stimulating and performing of minimally invasive surgical procedures.Trial Registration: ClinicalTrials.gov : registration number NCT02172690 . [ABSTRACT FROM AUTHOR]

Background Extramural venous invasion (EMVI) is defined histologically as the active invasion of tumor cells to the lumens of mesenteric vessels beyond the muscularis propria in advanced gastrointestinal cancer, resulting in distant metastases. Purpose To determine the association between synchronous metastatic disease in patients with T4 gastric cancer and EMVI detected on contrast-enhanced multiple-row detector computed tomography (MDCT). Material and Methods A total of 152 patients with T4 gastric carcinoma were retrospectively reviewed and divided into EMVI-positive and EMVI-negative groups where EMVI, as detected on MDCT, was defined as a tubular or nodular soft tissue thickening extending from the tumor along the vessels of the mesentery. Synchronous metastases were detected by MDCT and/or confirmed by postoperative diagnosis. Logistic regression analyses were performed to analyze the predictive factors of synchronous metastases in gastric cancer. Results Synchronous metastases were found in 47 of 152 (30.9%) patients with T4 gastric cancer. Thirty-one of 77 (40.3%) patients in the EMVI-positive group had evidence of metastases compared to 16 (21.3%) of 75 patients in the EMVI-negative group ( P = 0.019). Synchronous metastases were significantly associated with EMVI with an odds ratio (OR) of 2.250 (95% CI, 1.072-4.724). Conclusion EMVI-positive tumors, as an adverse imaging feature, were significantly associated with synchronous metastases in patients with T4 gastric cancer. [ABSTRACT FROM AUTHOR]

Background and Aim Increasing evidence has indicated that long noncoding ribonucleic acids ( lncRNAs) play a major role in cancers. Although certain lncRNAs has been reported to play a role in gastric cancer ( GC), specific lncRNAs involved in distant metastasis of GC remain unknown. Methods Differentially expressed mRNAs and lncRNAs between stage IV and non-stage IV GC were obtained by microarray. Gene ontology and pathway analysis were used to study functions of differential mRNAs. Algorithms were used to predict potential gene targets of cis or trans-acting lncRNAs. Network analysis was performed to analyze each pair of gene- lncRNA, gene-gene, or lncRNA-lncRNA interactions. Expression of lncRNA special for distant metastasis of GC ( SDMGC) and target gene TRIM16 were tested in GC tissues and cell lines. RNAi and overexpression were used to observe the biological functions of SDMGC and TRIM16 on GC cells. Results 502 mRNAs and 440 lncRNAs were found to be differentially expressed. 74 gene ontology terms and 38 pathways were associated with the dysregulated transcripts. Fourteen core factors were determined by network analysis. Expression of SDMGC and TRIM16 was upregulated in the distant metastasis tissues, compared with primary GC tissues, which were positive correlation. Silencing of SDMGC or TRIM16 was demonstrated to decrease cell invasion and migration, while upregulated of SDMGC or TRIM16 could promote cell invasion and migration. However, little effect on proliferation, cell cycle, colony formation, and apoptosis was found. Conclusions SDMGC is obviously upregulated in stage IV GC and may represent a new marker and therapeutic target for GC treatment. [ABSTRACT FROM AUTHOR]

Multifocal liposarcoma with different histological types is rare, especially that originating from the mesentery. We herein report a case of primary myxoid liposarcoma from the sigmoid mesocolon that was accompanied with well-differentiated liposarcomas in the pelvis. The location, the fat signal and the relationship with adjacent organs of the liposarcomas were well shown in the axial, coronal and sagittal dimensions of MRI, giving a comprehensive and specific image before surgery. To alleviate the patient's symptoms and mental stress, a laparotomy was performed. The tumors were all completely excised with macroscopic free margins. The final histopathological report showed that the tumor in the sigmoid mesocolon was a pure myxoid liposarcoma, while the pelvic tumors were spindle cell liposarcomas, a special type of well-differentiated liposarcoma. According to the AJCC staging system, they were all stage IIB. No further adjuvant therapy was performed. Close follow-up after the surgery has been performed, and the patient has remained healthy without any evidence of recurrence or metastasis for 17 months after the surgery. [ABSTRACT FROM AUTHOR]

N-cadherin is related to the progression and metastases of several solid carcinomas. However, it was still unclear whether N-cadherin is overexpressed in colorectal malignant tumors that have stronger malignant tendency. In this study, we used immunohistochemistry to detect the expression patterns of N-cadherin in both the primary tumors and their normal mucosa tissues of 120 patients with colorectal cancer. We revealed that N-cadherin was expressed in 78.3% (94/120) of colorectal tumor tissues and in only 9.2% (11/120) of paired distant normal mucosa tissues with a significant difference ( P=0.000). The low, moderate, and high expression of N-cadherin protein was 42.5%, 30.8%, and 26.7%, respectively. N-cadherin overexpression was associated with advanced TNM stage, lymph nodes metastasis and distant metastasis ( P<0.05). Patients with N-cadherin overexpressed showed the obvious lower overall survival rate than those with moderate and low expression, and patients with low expression had a better survival rate than those with moderate and high expression ( P<0.05). In conclusion, high N-cadherin expression may lead to tumor aggressiveness and metastatic potential in colorectal cancer, and may prove to be a possible prognostic factor. [ABSTRACT FROM AUTHOR]

Background. As previously demonstrated, tumor associated macrophages (TAMs) infiltration is associated with some cancers invasion and metastasis. However, the role of TAMs in the gastric cancer remains unclear. Methods Three- dimensional dynamic migration imaging system and real time RT-PCR were used to quantitatively investigate the effect of macrophages on the cancer cell mobility and gene expression related to cancer invasion and metastasis, including ADAM8, ADAM9, MMP9, TIMP3, VEGF-A and IL8 genes, in AGS, HGC-27, Hs-746T and NCI-N87 gastric cancer cell lines under normal or hypoxic conditions. Results. Under normal conditions, the cancer cell invasion rate was increased significantly and all six gene expressions were upregulated in all four cancer cell lines by macrophages. Under hypoxia the changes in the cancer cell invasion rate induced by macrophages was negatively correlated to the TIMP3 expression. In non- metastatic cell line AGS, the increase in migration rate induced by macrophages was further elevated under hypoxia with increased ADAM8 and ADAM9 expression and decreased MMP9 and TIMP3 expressions. Under hypoxia, the induction by macrophages for IL-8 expression was increased significantly in distant metastatic cell lines NCI-N87 and HS-746T, VEGF-A was increased in HGC-27 cell line. Conclusions. Both macrophages and hypoxia play an indispensable role in regulating the invasion of gastric cancer cells in vitro; ADAMs, MMP9 and TIMP3 might be involved in TAM induced invasive power of gastric cancer cells. [ABSTRACT FROM AUTHOR]

Abstract: Background: Kindlin-2 has been confirmed as an essential element of bidirectional integrin signaling. In recent years, the relationship between Kindlin-2 expression and cancers has been a focus of interest. However, the relationship between Kindlin-2 expression in gastric cancer and tumor invasion, metastasis, and the outcome of patients have not been studied. Methods: Kindlin-2 expression at protein and RNA levels were detected by Western blot and real-time polymerase chain reaction in 40 pairs of gastric cancer samples. In addition, the correlations between Kindlin-2 expression and clinicopathologic factors as well as the prognosis of the patients were analyzed. Multivariate Cox regression was used to study the effect of Kindlin-2 expression on overall and progression-free survival. Results: We found that Kindlin-2 was up-regulated both at RNA (P = .027) and protein levels (P = .014) in gastric cancer tissues. Tumor samples with high Kindlin-2 expression (Kindlin-2/β-actin:tumor tissue/paraneoplastic tissue, ≥2) was observed in 55% of the patients. Moreover, Kindlin-2 expression had a significant positive correlation with tumor stromal invasion (P = .014), lymph node metastasis (P = .007), and TNM stage (P = .014). Patients with high Kindlin-2 expression had significantly poorer overall survival (P = .012) and progression-free survival (P = .012). High Kindlin-2 expression was an independent risk factor of progression-free survival (hazard ratio, 5.2; 95% confidence interval, 1.1–3.3; P = .032). Conclusions: Kindlin-2 may play an important role in the development of gastric cancer and it is a potential factor that could be used to evaluate the outcome of gastric cancer. Kindlin-2 may shed new light on evaluating the prognosis and targeted therapy of gastric cancer. [Copyright &y& Elsevier]

Objective. N-myc downstream regulated gene-1 (NDRG1) is known as a differentiation-related gene that plays important roles in cell differentiation, organ formation, and embryonic development. NDRG1 was recently found to significantly down regulate in a variety of different neoplasms. Its significance in gastric cancer has not been studied. Materials and methods. NDRG1 was detected at its protein level by immunohistochemistry in formalin-fixed and paraffin-embedded sections with a total of 110 pair gastric cancer specimens including tumor and corresponding paraneoplastic tissues; NDRG1 mRNA was detected by real time-polymerase chain reaction. Meanwhile, the correlations between NDRG1 and clinicopathological factors were observed. Overexpression of NDRG1 has influence on the biological behavior of gastric cancer cell, which was detected by cell growth assay, apoptosis assay, and in vitro motility and invasion assay. Results. NDRG1 protein was down regulated in gastric cancer tissues, and the NDRG1 low expression rate was 73.6% (79/110). Moreover, NDRG1 expression has a significant inverse correlation with tumor stromal invasion, lymph node metastasis, pathological stage, but not with distant metastasis. The patients with low NDRG1 expression had a significantly shorter survival opportunity than those with high NDRG1 expression. In addition, overexpression of NDRG1 induced early apoptosis and inhibited SGC7901 cell proliferation and its motility and invasion capability. Conclusions. NDRG1 plays a significant role in carcinogenesis and preventing the metastasis and invasion of gastric cancer cells. NDRG1 could be developed as a marker contributing to diagnosis and evaluating prognosis in gastric cancer, as well as a potential therapeutic target of gastric cancer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies on how complete mesocolic excision (CME) affects prognosis indicate fundamental limitations that prevent the procedure from being completely accepted in practice. This study evaluated 5-year survival in colon cancer patients who underwent CME in a strict quality-controlled trial. STUDY DESIGN: A prospective, nonrandomized, double-blind, controlled trial recruited patients who underwent open radical resection for colon cancer between November 2012 and November 2017. Third-party experts evaluated whether patients had undergone mesocolic dissection and/or central ligation by looking at photographs of both surgical field and specimen, and then divided patients into CME and non-CME (NCME) groups. The primary outcome was the 5-year local recurrence-free survival rate. Clinicopathological and follow-up data were recorded. RESULTS: There were 261 patients with a median follow-up time of 57 months assigned to the CME group, and 129 patients with a median follow-up time of 59 months were assigned to the NCME group. The 5-year local recurrence-free survival rate of patients with Union Internationale Contre le Cancer stage I to III cancer did not differ significantly between the groups. For stage I to III cancer and stage III cancer, the absolute risk reduction of 5-year cumulative death and disease progression after CME were 9.1% (95% CI 1% to 17%; p = 0.033) and 16.1% (95% CI 1% to 31%; p = 0.040), respectively. Meanwhile, CME also could reduce 14% 5-year cumulative incidence recurrence for Union Internationale Contre le Cancer stage III cancer compared with NCME (CME, 27.3% vs NCME, 41.3%; p = 0.042) after adjusting for the effect of non-cancer-related death. CONCLUSIONS: CME should be considered as a standard surgical procedure in affected patients. [ABSTRACT FROM AUTHOR]