Socioeconomic disparities and the genomic landscape of gastric cancer.

The genomic characteristics of Peruvian patients with gastric adenocarcinoma from diverse socioeconomic backgrounds were examined in consideration of the possibility that patients from different socioeconomic backgrounds may be exposed to different risk factors. We conducted a prospective pilot study in two Peruvian cities (Lima and Ica). This study enrolled 15 patients from low socioeconomic status (LSES) and 15 patients from medium/high socioeconomic status (MHSES). The genomic profiling of gastric adenocarcinoma samples was done through the FoundationOne CDx platform. We compared the genomic characteristics and the need for targeted therapy and immunotherapy between LSES and MHSES. The genes with higher rates of alterations were TP53 (73.3% vs. 50.0%, P = 0.2635); CDH1 (26.7% vs. 28.6%, P = 1); CDKN2A (20.0% vs. 28.6%, P = 1); KRAS (33.3% vs. 7.1%, P = 0.1686); ARID1A (20.0% vs. 14.3%, P = 1); MLL2 (13.3% vs. 21.4%, P = 1) and SOX9 (33.3% vs. 0.0%, P = 0.0421) in LSES versus HMSES, respectively. There was no significant difference in tumor mutational burden (P = 0.377) or microsatellite status (P = 1). The LSES group had a higher need for targeted therapy or immunotherapy according to gene involvement and alterations. A significant genomic difference exists among patients with gastric adenocarcinoma of different socioeconomic status, which may result in a different need for targeted therapy and immunotherapy.

Gastric adenocarcinoma with high­level microsatellite instability: A case report.

Gastric cancer (GC) ranks fifth on the list of the most common malignancies worldwide. In Peru, gastric neoplasms are considered the second leading cause of mortality among males. Among the molecular subgroups of GC, microsatellite instability presents a favorable prognosis due to its hypermutated phenotype, which activates immunosurveillance. The present study describes the case of a 75-year-old patient, who was admitted in the hospital with a history of upper gastrointestinal bleeding and recurrent hospital admission, due to severe anemia. The patient presented with pale skin, normal vital functions, slight swelling of the lower extremities, and abdominal distention and bloating upon a physical examination. An endoscopic examination revealed an infiltrating circular ulcerated lesion. The histopathological analysis identified a moderately differentiated intestinal-type adenocarcinoma with pathological stage T3N0M0. Tumor genomic profiling demonstrated alterations in 15 different genes with a tumor mutational burden of 28 mutations/Mb. Finally, the patient underwent a partial gastrectomy without pre-operative chemotherapy. After 4 days, the patient presented with post-operative complications for which he was re-operated on. The patient did not survive. To the best of our knowledge, in the present case, pernicious anemia was an early sign of GC and a gastroscopy had to be performed. Furthermore, MutS homolog 3 alterations probably conditioned the presence of multiple frame-shift mutations.

Characteristics of gastric cancer around the world.

Gastric cancer is one of the most important malignancies in the world due to the high burden of disease and lethality. In this work, we compared the main characteristics of gastric cancer between different regions of the world. We reviewed public repositories to retrieve epidemiological, molecular, clinicopathological, and risk factor data. Eastern Asia presents the highest incidence of gastric cancer, followed by eastern and central Europe. Intestinal histology was more frequent in Caucasians, while gastric tumors located in the cardias were less frequent in Africa and Latin America. TP53, LRP1B, and ARID1A are consistently the most frequently altered genes in all population groups. Gastric cancer is most frequent in men. African patients tend to be younger and have a higher proportion of women patients. Different patterns can be observed in the presentation of gastric cancer between different regions of the world. More research is needed in Latin America and Africa since these populations are underrepresented.

Influence of Sex in the Molecular Characteristics and Outcomes of Malignant Tumors.

BACKGROUND: Sex is frequently underestimated as a prognostic biomarker in cancer. In this study, we evaluated a large cohort of patients and public datasets to determine the influence of sex on clinical outcomes, mutational status, and activation of immune pathways in different types of cancer. METHODS: A cohort of 13,619 Oncosalud-affiliated patients bearing sex-unrelated cancers was followed over a 20-year period. Hazard ratios (HRs) for death were estimated for female vs. male patients for each cancer type and then pooled in a meta-analysis to obtain an overall HR. In addition, the mutational status of the main actionable genes in melanoma (MEL), colorectal cancer (CRC), and lung cancer was compared between sexes. Finally, a gene set enrichment analysis (GSEA) of publicly available data was conducted, to assess differences in immune processes between sexes in MEL, gastric adenocarcinoma (GC), head and neck cancer (HNC), colon cancer (CC), liver cancer (LC), pancreatic cancer (PC), thyroid cancer (TC), and clear renal cell carcinoma (CCRCC). RESULTS: Overall, women had a decreased risk of death (HR = 0.73, CI95: 8%-42%), with improved overall survival (OS) in HNC, leukemia, lung cancer, lymphoma, MEL, multiple myeloma (MM), and non-melanoma skin cancer. Regarding the analysis of actionable mutations, only differences in EGFR alterations were observed (27.7% for men vs. 34.4% for women, p = 0.035). The number of differentially activated immune processes was higher in women with HNC, LC, CC, GC, MEL, PC, and TC and included cellular processes, responses to different stimuli, immune system development, immune response activation, multiorganism processes, and localization of immune cells. Only in CCRCC was a higher activation of immune pathways observed in men. CONCLUSIONS: The study shows an improved survival rate, increased activation of immune system pathways, and an enrichment of EGFR alterations in female patients of our cohort. Enhancement of the immune response in female cancer patients is a phenomenon that should be further explored to improve the efficacy of immunotherapy.