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2.
Article in English | MEDLINE | ID: mdl-38839368

ABSTRACT

Esophagogastric junction cancer (EGJC) is a rare malignant disease that occurs in the gastroesophageal transition zone. In recent years, its incidence has been rapidly increasing not only in Western countries but also in East Asia, and it has been attracting the attention of both clinicians and researchers. EGJC has a worse prognosis than gastric cancer (GC) and is characterized by complex lymphatic drainage pathways in the mediastinal and abdominal regions. EGJC was previously treated in the same way as GC or esophageal cancer, but, in recent years, it has been treated as an independent malignant disease, and treatment focusing only on EGJC has been developed. A recent multicenter prospective study revealed the frequency of lymph node metastasis by station and established the optimal extent of lymph node dissection. In perioperative treatment, the combination of multi-drug chemotherapy, radiation therapy, molecular targeted therapy, and immunotherapy is expected to improve the prognosis. In this review, we summarize previous clinical trials and their important evidence on surgical and perioperative treatments for EGJC.


Subject(s)
Esophageal Neoplasms , Esophagectomy , Esophagogastric Junction , Humans , Esophagogastric Junction/surgery , Esophagogastric Junction/pathology , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Esophageal Neoplasms/mortality , Esophageal Neoplasms/therapy , Treatment Outcome , Esophagectomy/adverse effects , Esophagectomy/mortality , Gastrectomy/mortality , Gastrectomy/adverse effects , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Lymph Node Excision , Chemotherapy, Adjuvant , Lymphatic Metastasis , Risk Factors , Neoadjuvant Therapy/adverse effects , Neoadjuvant Therapy/mortality
3.
Front Immunol ; 15: 1370367, 2024.
Article in English | MEDLINE | ID: mdl-38840920

ABSTRACT

Because of the considerable tumor heterogeneity in gastric cancer (GC), only a limited group of patients experiences positive outcomes from immunotherapy. Herein, we aim to develop predictive models related to glycosylation genes to provide a more comprehensive understanding of immunotherapy for GC. RNA sequencing (RNA-seq) data and corresponding clinical outcomes were obtained from GEO and TCGA databases, and glycosylation-related genes were obtained from GlycoGene DataBase. We identified 48 differentially expressed glycosylation-related genes and established a prognostic model (seven prognosis genes including GLT8D2, GALNT6, ST3GAL6, GALNT15, GBGT1, FUT2, GXYLT2) based on these glycosylation-related genes using the results from Cox regression analysis. We found that these glycosylation-related genes revealed a robust correlation with the abundance of Tumor Infiltrating Lymphocytes (TILs), especially the GLT8D2 which is associated with many TILs. Finally, we employed immunohistochemistry and Multiplex Immunohistochemical to discover that GLT8D2 serves as a valuable prognostic biomarker in GC and is closely associated with macrophage-related markers. Collectively, we established a prognostic model based on glycosylation-related genes to provide a more comprehensive understanding of prediction for GC prognosis, and identified that GLT8D2 is closely correlated with adverse prognosis and may underscore its role in regulating immune cell infiltration in GC patients.


Subject(s)
Biomarkers, Tumor , Lymphocytes, Tumor-Infiltrating , Stomach Neoplasms , Humans , Stomach Neoplasms/immunology , Stomach Neoplasms/genetics , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Biomarkers, Tumor/genetics , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Prognosis , Glycosylation , Female , Male , Gene Expression Regulation, Neoplastic , Middle Aged , Tumor Microenvironment/immunology
4.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 605-609, 2024 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-38825907

ABSTRACT

Objective: To investigate the clinicopathological features of children with metachronous or synchronous primary tumors and to identify related genetic tumor syndromes. Methods: The clinicopathological data of 4 children with multiple primary tumors diagnosed in the Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from 2011 to 2023 were collected. The histological, immunophenotypic and molecular characteristics were examined using H&E staining, immunohistochemical staining, PCR, Sanger sequencing and next-generation sequencing (NGS). The patients were followed up. Results: Case 1 was an 8-year-old boy with the adrenal cortical carcinoma, and 5 years later a poorly differentiated gastric adenocarcinoma was detected. Case 2 was a 2-year-old boy, presented with a left ventricular choroid plexus carcinoma, and a hepatoblastoma was detected 8 months later. Case 3 was a 9-month-old girl, diagnosed with renal rhabdoid tumor first and intracranial atypical teratoid/rhabdoid tumor (AT/RT) 3 months later. Case 4 was a 7-year-old boy and had a sigmoid colon adenocarcinoma 3 years after the diagnosis of a glioblastoma. The morphology and immunohistochemical features of the metachronous or synchronous primary tumors in the 4 cases were similar to the corresponding symptom-presenting/first-diagnosed tumors. No characteristic germ line mutations were detected in cases 1 and 2 by relevant molecular detection, and the rhabdoid tumor predisposition syndrome was confirmed in case 3 using NGS. Case 4 was clearly related to constitutional mismatch repair deficiency as shown by the molecular testing and clinical features. Conclusions: Childhood multiple primary tumors are a rare disease with histological morphology and immunophenotype similar to the symptom-presenting tumors. They are either sporadic or associated with a genetic (tumor) syndrome. The development of both tumors can occur simultaneously (synchronously) or at different times (metachronously). Early identification of the children associated with genetic tumor syndromes can facilitate routine tumor screening and early treatment.


Subject(s)
Hepatoblastoma , Kidney Neoplasms , Liver Neoplasms , Neoplasms, Multiple Primary , Rhabdoid Tumor , Stomach Neoplasms , Humans , Male , Child , Female , Child, Preschool , Neoplasms, Multiple Primary/genetics , Neoplasms, Multiple Primary/pathology , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Kidney Neoplasms/pathology , Kidney Neoplasms/genetics , Infant , Stomach Neoplasms/pathology , Stomach Neoplasms/genetics , Rhabdoid Tumor/genetics , Rhabdoid Tumor/pathology , Hepatoblastoma/genetics , Hepatoblastoma/pathology , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma/diagnosis , Choroid Plexus Neoplasms/genetics , Choroid Plexus Neoplasms/pathology , Choroid Plexus Neoplasms/diagnosis , Adrenocortical Carcinoma/genetics , Adrenocortical Carcinoma/pathology , Adrenal Cortex Neoplasms/pathology , Adrenal Cortex Neoplasms/genetics , Teratoma/pathology , Teratoma/genetics , Teratoma/surgery , Brain Neoplasms/genetics , Brain Neoplasms/pathology , SMARCB1 Protein/genetics , MutL Protein Homolog 1/genetics , Neoplasms, Second Primary/pathology , Neoplasms, Second Primary/genetics , High-Throughput Nucleotide Sequencing , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/pathology
5.
Zhonghua Yi Xue Za Zhi ; 104(21): 2003-2006, 2024 Jun 04.
Article in Chinese | MEDLINE | ID: mdl-38825945

ABSTRACT

To investigate the clinical characteristics of metastatic tumors in small intestine. The clinical manifestations, imaging and endoscopic findings, treatment methods and follow-up of patients with small bowel metastatic tumors admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to December 31, 2022 were retrospectively analyzed. A total of 10 patients were included, including 7 males and 3 females, aged 33-77 (56.4±12.6) years. The main clinical manifestations were intestinal obstruction (8 cases), such as abdominal pain, abdominal distension, nausea, vomiting, and reduced defecation. Some patients had intussusception (abdominal pain, vomiting, black stool and other symptoms, 1 case) or gastrointestinal bleeding (1 case) with early symptoms imperceptible. The primary tumors include gastric cancer (3 cases), malignant melanoma (2 cases), ovarian cancer (2 cases), colon cancer (1 case), rectal cancer (1 case), and lung cancer (1 case). Most of the primary tumors were poorly differentiated (6 cases) or moderately to poorly differentiated (2 cases). The median time from primary tumor surgery to detection of small bowel metastasis [M (Q1, Q3)] was 22 (18, 28) months.The metastatic lesions were single (6 cases) or multiple (4 cases), in both jejunum and ileum. Positron emission tomography-computed tomography (PET-CT, 3 cases) and endoscopy (2 cases) were helpful for detection of small intestinal metastases. The main treatment methods were surgical resection (9 cases), supplemented by radiotherapy, targeted drugs, immunotherapy, etc. Postoperative recurrence and metastasis occurred in some patients (5 cases). Most patients died within 4 to 29 months after diagnosis. Metastatic tumors in small intestine are rare in clinical practice with atypical early symptoms. The patients often present with complications such as intestinal obstruction, which is prone to delayed diagnosis and poor prognosis.


Subject(s)
Intestinal Neoplasms , Intestine, Small , Humans , Female , Middle Aged , Male , Aged , Intestine, Small/pathology , Adult , Retrospective Studies , Intestinal Neoplasms/pathology , Intestinal Obstruction/etiology , Melanoma/pathology , Stomach Neoplasms/pathology
6.
Pak J Pharm Sci ; 37(2(Special)): 443-450, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38822548

ABSTRACT

Gastric cancer remains a global health concern, driving the exploration of natural products with anticancer potential. This study investigated the antiproliferative activity and chemical composition of a 70% ethanolic extract from Melissa officinalis L. against human gastric cancer cells. The extract was prepared and evaluated for total phenolic content, antioxidant capacity and flavonoid content. The MTT test checked how well it stopped the growth of human gastric adenocarcinoma (AGS) and normal dermal fibroblast (HDF) cells. Data analysis (SPSS Statistics) determined viable cell percentages and performed regression analysis (p<0.05). The extract exhibited significant antiproliferative activity against AGS cells compared to normal cells (p<0.05), with decreasing IC50 values (564.3, 258.0 and 122.5 µg/ml) over 24, 48 and 72 hours. It also displayed antioxidant activity (IC50=16.8±1.41µg/ml) and contained substantial phenolics (225.76±4.1 mg GAE/g) and flavonoids (22.36±2.6 mg RUT/g). This study suggests the 70% ethanolic extract of M. officinalis effectively suppresses AGS cell growth and possesses promising antioxidant properties, highlighting its potential as a natural source of anticancer and antioxidant agents, deserving further investigation.


Subject(s)
Adenocarcinoma , Antineoplastic Agents, Phytogenic , Antioxidants , Cell Proliferation , Melissa , Phenols , Plant Extracts , Stomach Neoplasms , Humans , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Melissa/chemistry , Phenols/pharmacology , Phenols/analysis , Cell Line, Tumor , Antioxidants/pharmacology , Antioxidants/isolation & purification , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , Flavonoids/pharmacology , Flavonoids/analysis , Cell Survival/drug effects
7.
Langenbecks Arch Surg ; 409(1): 174, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38837064

ABSTRACT

BACKGROUND: Despite being oncologically acceptable for esophagogastric junction adenocarcinoma with an esophageal invasion length of 3-4 cm, the transhiatal approach has not yet become a standard method given the difficulty of reconstruction in a narrow space and the risk of severe anastomotic leakage. This study aimed to clarify the safety and feasibility of the open left diaphragm method during the transhiatal approach for esophagogastric junction adenocarcinoma. METHODS: This retrospective study compared the clinical outcomes of patients who underwent proximal or total gastrectomy with lower esophagectomy for Siewert type II/III adenocarcinomas with esophageal invasion via the laparoscopic transhiatal approach with or without the open left diaphragm method from April 2013 to December 2021. RESULTS: Overall, 42 and 13 patients did and did not undergo surgery with the open left diaphragm method, respectively. The median operative time was only slightly shorter in the open left diaphragm group than in the non-open left diaphragm group (369 vs. 482 min; P = 0.07). Grade ≥ II postoperative respiratory complications were significantly less common in the open left diaphragm group than in the non-open left diaphragm group (17% vs. 46%, P = 0.03). Neither group had grade ≥ IV anastomotic leakage, and two cases of anastomotic leakage requiring reoperation were drained using the left diaphragmatic release technique. CONCLUSIONS: Transhiatal lower esophagectomy with gastrectomy using the open left diaphragm method is safe, highlighting its advantages for Siewert type II/III esophagogastric junction adenocarcinoma with an esophageal invasion length of ≤ 4 cm.


Subject(s)
Adenocarcinoma , Diaphragm , Esophageal Neoplasms , Esophagectomy , Esophagogastric Junction , Gastrectomy , Laparoscopy , Stomach Neoplasms , Humans , Esophagogastric Junction/surgery , Adenocarcinoma/surgery , Adenocarcinoma/pathology , Female , Male , Retrospective Studies , Middle Aged , Laparoscopy/methods , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Aged , Gastrectomy/methods , Esophagectomy/methods , Diaphragm/surgery , Stomach Neoplasms/surgery , Stomach Neoplasms/pathology , Plastic Surgery Procedures/methods
8.
Cancer Rep (Hoboken) ; 7(6): e2101, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38831124

ABSTRACT

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is a rare and aggressive subtype of gastric cancer (GC), accounting for less than 1% of all cases. It is characterized by frequent liver metastasis recurrence and a poorer prognosis than conventional GC. However, established treatment guidelines for HAS are currently not available.In this report, we present the results of a clinicopathological study of 19 patients diagnosed with HAS, including seven patients with liver metastasis, conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO) between 2016 and 2018. AIMS: The aim of the study was to retrospectively observe the outcomes of HAS with gastrectomy and hepatectomy for liver metastasis and determine relevant prognostic factor. We also examined the criteria and outcomes of hepatectomy for liver metastasis and aimed to suggest the optimal treatment for HAS, including chemotherapy. METHODS AND RESULTS: A total of 2147 patients underwent gastrectomy for GC at HiSCO-affiliated institutions during the study period; 19 patients, all male with a mean age of 70.9 years, were diagnosed with HAS by hematoxylin-eosin and immunohistochemical staining. Patients underwent gastrectomy at varying pathological stages: six at Stage I, three at Stage II, seven at Stage III, and three at Stage IV. Ten patients received postoperative chemotherapy and the 5-year survival rate was 67.7% after gastrectomy. Among the seven patients with pre or postoperative liver metastasis, five patients underwent hepatectomy. Although one patient had recurrence, the 3-year survival rate was 100% after hepatectomy. CONCLUSION: Contrary to previous reports suggesting a 3-year survival rate of approximmately 30% for HAS, our findings indicate that the prognosis for HAS may not be as poor as reported previously. This study contributes valuable insights into the management and potential treatment strategies for HAS.


Subject(s)
Adenocarcinoma , Gastrectomy , Hepatectomy , Liver Neoplasms , Stomach Neoplasms , Humans , Male , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Stomach Neoplasms/surgery , Retrospective Studies , Aged , Middle Aged , Adenocarcinoma/pathology , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Adenocarcinoma/surgery , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/mortality , Liver Neoplasms/therapy , Prognosis , Survival Rate , Aged, 80 and over , Neoplasm Staging , Neoplasm Recurrence, Local/pathology , Female
9.
Cancer Immunol Immunother ; 73(8): 144, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832979

ABSTRACT

BACKGROUND: The beneficial effects of first-line programmed death-1 (PD-1) inhibitors plus chemotherapy in patients with low programmed death-ligand 1 (PD-L1)-expressing advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma are controversial. METHODS: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with PD-1 inhibitors plus chemotherapy between October 2017 and May 2022. The primary outcomes were objective response rate (ORR) and progression-free survival (PFS). SPSS software V27.0 was used for data analysis. RESULTS: Of 345 enrolled patients, 290 had measurable lesions. The overall ORR was 59.3%. PD-L1 status was available in 171 patients, and 67.8% of them were considered as low PD-L1 expression level (combined positive score (CPS) < 5). Patients with PD-L1 CPS < 5 showed a lower response rate (51.1% vs 70.8%, P = 0.024) and a worse PFS (P = 0.009) compared to those with PD-L1 CPS ≥ 5. In the PD-L1 low-expression cohort, patients with non-diffuse type, GEJ cancer, synchronous metastasis, distant lymph node metastasis, liver metastasis, non-peritoneal metastasis, and HER2 positive were significantly associated with higher response rates to PD-1 inhibitors plus chemotherapy (P < 0.05). The presence of peritoneal metastasis (P = 0.028) and diffuse type (P = 0.046) were identified as independent predictors of poor PFS in multivariate analysis of the PD-L1 CPS < 5 subgroup. When evaluated for correlation with overall survival (OS) in the PD-L1 low-expression subgroup, peritoneal metastasis was found to be the only independent prognostic factor of an increased risk of death (hazard ratio: 2.31, 95% CI 1.09-4.90; P = 0.029). CONCLUSIONS: PD-L1 CPS ≥ 5 is significantly associated with improved response and extended PFS in G/GEJ cancer patients treated with a combination of PD-1 inhibitors and chemotherapy. Specific subgroups within the low PD-L1-expressing population, such as those with non-diffuse-type tumors and without peritoneal metastases, may also benefit from immunotherapy combined with chemotherapy.


Subject(s)
Adenocarcinoma , Antineoplastic Combined Chemotherapy Protocols , B7-H1 Antigen , Biomarkers, Tumor , Esophageal Neoplasms , Esophagogastric Junction , Immune Checkpoint Inhibitors , Stomach Neoplasms , Humans , Male , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Female , Middle Aged , Esophagogastric Junction/pathology , Esophagogastric Junction/metabolism , Adenocarcinoma/drug therapy , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/pathology , B7-H1 Antigen/metabolism , B7-H1 Antigen/antagonists & inhibitors , Aged , Retrospective Studies , Biomarkers, Tumor/metabolism , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Immune Checkpoint Inhibitors/therapeutic use , Aged, 80 and over , Prognosis
10.
BMC Cancer ; 24(1): 681, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834966

ABSTRACT

BACKGROUND: Our previous studies have indicated that mRNA and protein levels of PPIH are significantly upregulated in Hepatocellular Carcinoma (LIHC) and could act as predictive biomarkers for patients with LIHC. Nonetheless, the expression and implications of PPIH in the etiology and progression of common solid tumors have yet to be explored, including its potential as a serum tumor marker. METHODS: We employed bioinformatics analyses, augmented with clinical sample evaluations, to investigate the mRNA and protein expression and gene regulation networks of PPIH in various solid tumors. We also assessed the association between PPIH expression and overall survival (OS) in cancer patients using Kaplan-Meier analysis with TCGA database information. Furthermore, we evaluated the feasibility and diagnostic efficacy of PPIH as a serum marker by integrating serological studies with established clinical tumor markers. RESULTS: Through pan-cancer analysis, we found that the expression levels of PPIH mRNA in multiple tumors were significantly different from those in normal tissues. This study is the first to report that PPIH mRNA and protein levels are markedly elevated in LIHC, Colon adenocarcinoma (COAD), and Breast cancer (BC), and are associated with a worse prognosis in these cancer patients. Conversely, serum PPIH levels are decreased in patients with these tumors (LIHC, COAD, BC, gastric cancer), and when combined with traditional tumor markers, offer enhanced sensitivity and specificity for diagnosis. CONCLUSION: Our findings propose that PPIH may serve as a valuable predictive biomarker in tumor patients, and its secreted protein could be a potential serum marker, providing insights into the role of PPIH in cancer development and progression.


Subject(s)
Biomarkers, Tumor , Humans , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Prognosis , Female , Liver Neoplasms/genetics , Liver Neoplasms/blood , Liver Neoplasms/mortality , Gene Expression Regulation, Neoplastic , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/diagnosis , Neoplasms/genetics , Neoplasms/blood , Neoplasms/mortality , Neoplasms/diagnosis , Male , Computational Biology/methods , RNA, Messenger/genetics , RNA, Messenger/metabolism , Kaplan-Meier Estimate , Breast Neoplasms/genetics , Breast Neoplasms/blood , Breast Neoplasms/mortality , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Stomach Neoplasms/genetics , Stomach Neoplasms/blood , Stomach Neoplasms/diagnosis , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Colonic Neoplasms/genetics , Colonic Neoplasms/blood , Colonic Neoplasms/diagnosis , Colonic Neoplasms/pathology , Colonic Neoplasms/mortality , Gene Regulatory Networks
11.
Hum Genomics ; 18(1): 55, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822443

ABSTRACT

BACKGROUND: Although CDKN2A alteration has been explored as a favorable factor for tumorigenesis in pan-cancers, the association between CDKN2A point mutation (MUT) and intragenic deletion (DEL) and response to immune checkpoint inhibitors (ICIs) is still disputed. This study aims to determine the associations of CDKN2A MUT and DEL with overall survival (OS) and response to immune checkpoint inhibitors treatment (ICIs) among pan-cancers and the clinical features of CDKN2A-altered gastric cancer. METHODS: This study included 45,000 tumor patients that underwent tumor sequencing across 33 cancer types from four cohorts, the MSK-MetTropism, MSK-IMPACT, OrigiMed2020 and TCGA cohorts. Clinical outcomes and genomic factors associated with response to ICIs, including tumor mutational burden, copy number alteration, neoantigen load, microsatellite instability, tumor immune microenvironment and immune-related gene signatures, were collected in pan-cancer. Clinicopathologic features and outcomes were assessed in gastric cancer. Patients were grouped based on the presence of CDKN2A wild type (WT), CDKN2A MUT, CDKN2A DEL and CDKN2A other alteration (ALT). RESULTS: Our research showed that CDKN2A-MUT patients had shorter survival times than CDKN2A-WT patients in the MSK MetTropism and TCGA cohorts, but longer OS in the MSK-IMPACT cohort with ICIs treatment, particularly in patients having metastatic disease. Similar results were observed among pan-cancer patients with CDKN2A DEL and other ALT. Notably, CDKN2A ALT frequency was positively related to tumor-specific objective response rates to ICIs in MSK MetTropism and OrigiMed 2020. Additionally, individuals with esophageal carcinoma or stomach adenocarcinoma who had CDKN2A MUT had poorer OS than patients from the MSK-IMPACT group, but not those with adenocarcinoma. We also found reduced levels of activated NK cells, T cells CD8 and M2 macrophages in tumor tissue from CDKN2A-MUT or DEL pan-cancer patients compared to CDKN2A-WT patients in TCGA cohort. Gastric cancer scRNA-seq data also showed that CDKN2A-ALT cancer contained less CD8 T cells but more exhausted T cells than CDKN2A-WT cancer. A crucial finding of the pathway analysis was the inhibition of three immune-related pathways in the CDKN2A ALT gastric cancer patients, including the interferon alpha response, inflammatory response, and interferon gamma response. CONCLUSIONS: This study illustrates the CDKN2A MUT and DEL were associated with a poor outcome across cancers. CDKN2A ALT, on the other hand, have the potential to be used as a biomarker for choosing patients for ICI treatment, notably in esophageal carcinoma and stomach adenocarcinoma.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p16 , Stomach Neoplasms , Tumor Microenvironment , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/immunology , Cyclin-Dependent Kinase Inhibitor p16/genetics , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Male , Female , Immune Checkpoint Inhibitors/therapeutic use , Middle Aged , Biomarkers, Tumor/genetics , Aged , Prognosis , DNA Copy Number Variations/genetics , Mutation/genetics , Microsatellite Instability
12.
JCO Precis Oncol ; 8: e2400230, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38822761

ABSTRACT

PURPOSE: The clinical application of PD-L1 immunohistochemistry (IHC) testing is complicated by the availability of multiple IHC assays, scoring algorithms, and cutoffs. This study assessed the analytical comparability of three commercially available PD-L1 assays and two scoring algorithms used to assess PD-L1 status in gastric cancer (GC) samples. METHODS: Serial sections of 100 resected GC samples, with PD-L1 expression levels across the dynamic range, were stained with three in vitro diagnostic-grade PD-L1 assays (28-8, 22C3, and SP263). Three trained pathologists blindly and independently scored slides using combined positive score (CPS) and tumor area positivity (TAP) algorithms. Comprehensive statistical analyses were performed to evaluate analytical concordance. Digital image analysis (DIA) was used to objectively compare the technical performance of each assay by simulating CPS and TAP. RESULTS: Comparable staining patterns were observed with these three PD-L1 assays. Despite discernible variation in staining intensity, reproducible evaluations of PD-L1 positivity were observed. Inter- and intra-assay assessments of all three assays, using either CPS or TAP and the same PD-L1 cutoffs, demonstrated moderate to almost-perfect (interassay Cohen's kappa [κ] range, 0.47-0.83) and substantial to almost-perfect (intra-assay κ range, 0.77-1.00) agreement. Interpathologist assessment exhibited a significant level of concordance (intraclass correlation coefficient ≥0.92). No difference in technical performance was observed using DIA. CONCLUSION: This study highlights analytical concordance in PD-L1 testing between three major PD-L1 assays when TAP and CPS are applied. Comparability of the technical assay performance was further supported by independent DIA. These observations support cross-application flexibility of the different PD-L1 assays and scoring algorithms to characterize PD-L1 expression in GC.


Subject(s)
B7-H1 Antigen , Immunohistochemistry , Stomach Neoplasms , Humans , Stomach Neoplasms/pathology , Stomach Neoplasms/metabolism , B7-H1 Antigen/analysis , Immunohistochemistry/methods , Male , Female , Algorithms
13.
Cancer Med ; 13(11): e7326, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38826114

ABSTRACT

BACKGROUND: Optimal adjuvant chemotherapy after laparoscopic surgery in gastric cancer (GC) patients is still undefined. We aimed to evaluate the efficacy of S-1 plus oxaliplatin (SOX) and capecitabine plus oxaliplatin (CAPOX) in patients with GC after laparoscopic gastrectomy. METHODS: A non-inferiority randomized controlled clinical trial was performed in China. Patients with advanced GC who underwent laparoscopic D2 gastrectomy were randomly assigned to receive SOX and CAPOX regimens. RESULTS: In total, 191 patients were screened between May 2018 and June 2019, and 140 (73.3%) were included in the modified intent-to-treat analysis (mITT), of whom 69 and 71 were assigned to the SOX and CAPOX groups, respectively. The SOX group had similar 3-year overall survival (OS) and disease-free survival to the CAPOX group. Subgroup analysis revealed significantly better OS in the SOX group for male patients ([HR] = 0.395; 95% [CI], 0.153-1.019; p = 0.045), age >60 (HR = 0.219; 95% [CI], 0.064-0.753; p = 0.016), tumors in the gastric antrum (HR = 0.273; 95% [CI], 0.076-0.981; p = 0.047), and moderately differentiated tumors (HR = 0.338; 95% [CI], 0.110-1.041; p = 0.041). There were no significant differences observed in terms of adverse events and recurrence patterns between the two groups. CONCLUSION: Adjuvant SOX was non-inferior to CAPOX treatments for patients with GC who underwent curative laparoscopic D2 gastrectomy. For male patients, aged >60 years, tumors in the gastric antrum, and moderately differentiated tumors, adjuvant SOX may achieve an improvement compared with CAPOX.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Capecitabine , Drug Combinations , Gastrectomy , Laparoscopy , Oxaliplatin , Oxonic Acid , Stomach Neoplasms , Tegafur , Humans , Stomach Neoplasms/surgery , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/mortality , Male , Gastrectomy/methods , Female , Middle Aged , Laparoscopy/methods , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Oxaliplatin/therapeutic use , Oxaliplatin/administration & dosage , Tegafur/therapeutic use , Tegafur/administration & dosage , Oxonic Acid/therapeutic use , Oxonic Acid/administration & dosage , Chemotherapy, Adjuvant/methods , Capecitabine/administration & dosage , Capecitabine/therapeutic use , Aged , Adult
14.
J Pathol Clin Res ; 10(4): e12387, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38860888

ABSTRACT

Gastric poorly cohesive carcinoma (PCC) manifests with a diffuse pattern and diverse tumor cell morphologies, often indicating a more unfavorable prognosis. Recent consensus has reclassified PCC based on the proportion of signet-ring cells (SRCs) in tumors for research purposes. The two most distinct subtypes, poorly cohesive carcinoma not otherwise specified (PCC-NOS) and signet-ring cell carcinoma (SRCC), are characterized by less than 10% and more than 90% SRCs, respectively. However, research comparing the clinicopathological and transcriptomic differences between these subtypes remains limited. In this study, we conducted a comparative analysis of clinicopathological features in 55 advanced-stage PCCs, consisting of 43 PCC-NOS and 12 SRCC cases. Subsequently, 12 PCC-NOS and 5 SRCC cases were randomly selected for initial cancer-related gene expression profiling and pathway enrichment analysis using the GeoMx digital spatial profiler, followed by validation in a separate validation group comprising 16 PCC-NOS and 6 SRCC cases. These transcriptomic findings were then correlated with tumor morphology and clinicopathological data. PCC-NOS cases exhibited larger tumor size, a higher prevalence of pathological N3 disease, and a worse 1-year progression-free survival rate compared to SRCC cases. Clustering of PCC-NOS and SRCC was successfully achieved using the GeoMx Cancer Transcriptome Atlas. Among all studied genes, only MMP7 showed differential expression, with its overexpression significantly associated with the PCC-NOS subtype, increased perineural invasion, and earlier disease progression. Pathway analysis revealed significantly enriched pathways in PCC-NOS related to vesicle-mediated transport, adaptive immune systems, oncogenic signaling, and extracellular matrix organization, while SRCC displayed significant enrichment in pathways associated with respiratory electron transport and the cell cycle. In conclusion, this study compares and correlates clinicopathological features and transcriptomic data between PCC-NOS and SRCC at advanced stages, employing the latest consensus classification and a novel platform for analysis.


Subject(s)
Carcinoma, Signet Ring Cell , Gene Expression Profiling , Stomach Neoplasms , Transcriptome , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Male , Female , Middle Aged , Aged , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/genetics , Gene Expression Regulation, Neoplastic , Adult , Biomarkers, Tumor/genetics , Aged, 80 and over , Progression-Free Survival , Prognosis
15.
Sci Rep ; 14(1): 13127, 2024 06 07.
Article in English | MEDLINE | ID: mdl-38849404

ABSTRACT

Improvement in the survival rate of gastric cancer, a prevalent global malignancy and the leading cause of cancer-related mortality calls for more avenues in molecular therapy. This work aims to comprehend drug resistance and explore multiple-drug combinations for enhanced therapeutic treatment. An endogenous network modeling clinic data with core gastric cancer molecules, functional modules, and pathways is constructed, which is then transformed into dynamics equations for in-silicon studies. Principal component analysis, hierarchical clustering, and K-means clustering are utilized to map the attractor domains of the stochastic model to the normal and pathological phenotypes identified from the clinical data. The analyses demonstrate gastric cancer as a cluster of stable states emerging within the stochastic dynamics and elucidate the cause of resistance to anti-VEGF monotherapy in cancer treatment as the limitation of the single pathway in preventing cancer progression. The feasibility of multiple objectives of therapy targeting specified molecules and/or pathways is explored. This study verifies the rationality of the platform of endogenous network modeling, which contributes to the development of cross-functional multi-target combinations in clinical trials.


Subject(s)
Stomach Neoplasms , Stomach Neoplasms/drug therapy , Stomach Neoplasms/pathology , Stomach Neoplasms/metabolism , Humans , Drug Resistance, Neoplasm , Models, Biological , Molecular Targeted Therapy/methods , Cluster Analysis , Principal Component Analysis , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Signal Transduction/drug effects
16.
BMC Cancer ; 24(1): 711, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858653

ABSTRACT

BACKGROUND: Inflammatory factors have increasingly become a more cost-effective prognostic indicator for gastric cancer (GC). The goal of this study was to develop a prognostic score system for gastric cancer patients based on inflammatory indicators. METHODS: Patients' baseline characteristics and anthropometric measures were used as predictors, and independently screened by multiple machine learning(ML) algorithms. We constructed risk scores to predict overall survival in the training cohort and tested risk scores in the validation. The predictors selected by the model were used in multivariate Cox regression analysis and developed a nomogram to predict the individual survival of GC patients. RESULTS: A 13-variable adaptive boost machine (ADA) model mainly comprising tumor stage and inflammation indices was selected in a wide variety of machine learning models. The ADA model performed well in predicting survival in the validation set (AUC = 0.751; 95% CI: 0.698, 0.803). Patients in the study were split into two sets - "high-risk" and "low-risk" based on 0.42, the cut-off value of the risk score. We plotted the survival curves using Kaplan-Meier analysis. CONCLUSION: The proposed model performed well in predicting the prognosis of GC patients and could help clinicians apply management strategies for better prognostic outcomes for patients.


Subject(s)
Biomarkers, Tumor , Nomograms , Stomach Neoplasms , Humans , Stomach Neoplasms/mortality , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology , Female , Male , Prognosis , China/epidemiology , Middle Aged , Aged , Inflammation , Machine Learning , Cohort Studies , Kaplan-Meier Estimate , Adult , Neoplasm Staging , Proportional Hazards Models
17.
Biomed Eng Online ; 23(1): 53, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858706

ABSTRACT

BACKGROUND: Metastasis is one of the main factors leading to the high mortality rate of gastric cancer. The current monitoring methods are not able to accurately monitor gastric cancer metastasis. METHODS: In this paper, we constructed a new type of hollow Mn 3 O 4 nanocomposites, Mn 3 O 4 @HMSN-Cy7.5-FA, which had a size distribution of approximately 100 nm and showed good stability in different liquid environments. The in vitro magnetic resonance imaging (MRI) results show that the nanocomposite has good response effects to the acidic microenvironment of tumors. The acidic environment can significantly enhance the contrast of T 1 -weighted MRI. The cellular uptake and endocytosis results show that the nanocomposite has good targeting capabilities and exhibits good biosafety, both in vivo and in vitro. In a gastric cancer nude mouse orthotopic metastatic tumor model, with bioluminescence imaging's tumor location information, we realized in vivo MRI/fluorescence imaging (FLI) guided precise monitoring of the gastric cancer orthotopic and metastatic tumors with this nanocomposite. RESULTS: This report demonstrates that Mn 3 O 4 @HMSN-Cy7.5-FA nanocomposites is a promising nano-diagnostic platform for the precision diagnosis and therapy of gastric cancer metastasis in the future. CONCLUSIONS: In vivo MRI/FLI imaging results show that the nanocomposites can achieve accurate monitoring of gastric cancer tumors in situ and metastases. BLI's tumor location information further supports the good accuracy of MRI/FLI dual-modality imaging. The above results show that the MHCF NPs can serve as a good nano-diagnostic platform for precise in vivo monitoring of tumor metastasis. This nanocomposite provides more possibilities for the diagnosis and therapy of gastric cancer metastases.


Subject(s)
Folic Acid , Magnetic Resonance Imaging , Nanocomposites , Neoplasm Metastasis , Stomach Neoplasms , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Animals , Nanocomposites/chemistry , Mice , Cell Line, Tumor , Humans , Folic Acid/chemistry , Manganese Compounds/chemistry , Optical Imaging , Mice, Nude , Oxides
18.
Mol Cancer ; 23(1): 124, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849840

ABSTRACT

BACKGROUND: Intestinal metaplasia (IM) is classified into complete intestinal metaplasia (CIM) and incomplete intestinal metaplasia (IIM). Patients diagnosed with IIM face an elevated susceptibility to the development of gastric cancer, underscoring the critical need for early screening measures. In addition to the complexities associated with diagnosis, the exact mechanisms driving the progression of gastric cancer in IIM patients remain poorly understood. OLFM4 is overexpressed in several types of tumors, including colorectal, gastric, pancreatic, and ovarian cancers, and its expression has been associated with tumor progression. METHODS: In this study, we used pathological sections from two clinical centers, biopsies of IM tissues, precancerous lesions of gastric cancer (PLGC) cell models, animal models, and organoids to explore the role of OLFM4 in IIM. RESULTS: Our results show that OLFM4 expression is highly increased in IIM, with superior diagnostic accuracy of IIM when compared to CDX2 and MUC2. OLFM4, along with MYH9, was overexpressed in IM organoids and PLGC animal models. Furthermore, OLFM4, in combination with Myosin heavy chain 9 (MYH9), accelerated the ubiquitination of GSK3ß and resulted in increased ß-catenin levels through the Wnt signaling pathway, promoting the proliferation and invasion abilities of PLGC cells. CONCLUSIONS: OLFM4 represents a novel biomarker for IIM and could be utilized as an important auxiliary means to delimit the key population for early gastric cancer screening. Finally, our study identifies cell signaling pathways involved in the progression of IM.


Subject(s)
Disease Progression , Glycogen Synthase Kinase 3 beta , Metaplasia , Myosin Heavy Chains , beta Catenin , Humans , Metaplasia/metabolism , Metaplasia/pathology , Metaplasia/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Animals , beta Catenin/metabolism , beta Catenin/genetics , Mice , Myosin Heavy Chains/metabolism , Myosin Heavy Chains/genetics , Stomach Neoplasms/pathology , Stomach Neoplasms/metabolism , Stomach Neoplasms/genetics , Female , Wnt Signaling Pathway , Cell Proliferation , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Disease Models, Animal , Male , Organoids/metabolism , Organoids/pathology
19.
Arch Iran Med ; 27(6): 341-345, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38855804

ABSTRACT

Macroscopic tumor implants in the hernia sac are a very rare condition. They occur as a result of the implantation of malignant cells in the malignant ascites from the inguinal canal to the hernia sac. In this case report, we share the clinical and radiological findings of the macroscopic tumoral implants in the hernia sac at the level of the inguinal canal and scrotum in a male patient aged 65 years with a history of total gastrectomy for gastric adenocarcinoma and developing malignant ascites six months after the surgery.


Subject(s)
Adenocarcinoma , Hernia, Inguinal , Stomach Neoplasms , Humans , Male , Stomach Neoplasms/pathology , Stomach Neoplasms/diagnostic imaging , Hernia, Inguinal/diagnostic imaging , Hernia, Inguinal/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Aged , Gastrectomy , Tomography, X-Ray Computed , Ascites/etiology , Ascites/diagnostic imaging
20.
BMC Cancer ; 24(1): 685, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840106

ABSTRACT

BACKGROUND: Gastric cancer is one of the most common tumors worldwide, and most patients are deprived of treatment options when diagnosed at advanced stages. PRDM14 has carcinogenic potential in breast and non-small cell lung cancer. however, its role in gastric cancer has not been elucidated. METHODS: We aimed to elucidate the expression of PRDM14 using pan-cancer analysis. We monitored the expression of PRDM14 in cells and patients using quantitative polymerase chain reaction, western blotting, and immunohistochemistry. We observed that cell phenotypes and regulatory genes were influenced by PRDM14 by silencing PRDM14. We evaluated and validated the value of the PRDM14-derived prognostic model. Finally, we predicted the relationship between PRDM14 and small-molecule drug responses using the Connectivity Map and The Genomics of Drug Sensitivity in Cancer databases. RESULTS: PRDM14 was significantly overexpressed in gastric cancer, which identified in cell lines and patients' tissues. Silencing the expression of PRDM14 resulted in apoptosis promotion, cell cycle arrest, and inhibition of the growth and migration of GC cells. Functional analysis revealed that PRDM14 acts in epigenetic regulation and modulates multiple DNA methyltransferases or transcription factors. The PRDM14-derived differentially expressed gene prognostic model was validated to reliably predict the patient prognosis. Nomograms (age, sex, and PRDM14-risk score) were used to quantify the probability of survival. PRDM14 was positively correlated with sensitivity to small-molecule drugs such as TPCA-1, PF-56,227, mirin, and linsitinib. CONCLUSIONS: Collectively, our findings suggest that PRDM14 is a positive regulator of gastric cancer progression. Therefore, it may be a potential therapeutic target for gastric cancer.


Subject(s)
DNA-Binding Proteins , Gene Expression Regulation, Neoplastic , Stomach Neoplasms , Transcription Factors , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Stomach Neoplasms/drug therapy , Stomach Neoplasms/metabolism , Humans , Transcription Factors/genetics , Transcription Factors/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Prognosis , Cell Line, Tumor , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Female , Male , Nomograms , Apoptosis , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Proliferation , Epigenesis, Genetic
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