Circulating Exosomal MicroRNA Signature Predicts Peritoneal Metastasis in Patients with Advanced Gastric Cancer.

BACKGROUND: Despite a radical operation, about half of gastric cancer (GC) patients with advanced GC experience peritoneal metastasis (PM), and the patients with PM have a poor prognosis. However, because staging laparoscopy was a highly invasive procedure for patients, identification of PM using a liquid biopsy can be useful for patients with GC. METHODS: This study analyzed two genome-wide miRNA expression profiling datasets (GSE164174 and TCGA). The study prioritized biomarkers in pretreatment plasma specimens from clinical training and validation cohorts of patients with GC. The authors developed an integrated exosomal miRNA panel and established a risk-stratification model, which was combined with the miRNA panel and currently used tumor markers (CEA, CA19-9, CA125, and CA72-4 levels). RESULTS: The comprehensive discovery effort identified a four-miRNA panel that robustly predicted the metastasis with excellent accuracy in the TCGA dataset (area under the curve [AUC] 0.86). A circulating exosomal miRNA panel was established successfully with remarkable diagnostic accuracy in the clinical training (AUC 0.85) and validation (AUC 0.86) cohorts. Moreover, the predictive accuracy of the panel was significantly superior to that of conventional clinical factors (P < 0.01), and the risk-stratification model was dramatically superior to the panel and currently used clinical factors for predicting PM (AUC 0.94; univariate: odds ratio [OR] 77.00 [P < 0.01]; multivariate OR 57.71 [P = 0.01]). CONCLUSIONS: The novel risk-stratification model for predicting PM has potential for clinical translation as a liquid biopsy assay for patients with GC. The study findings highlight the potential clinical impact of the model for improved selection and management of patients with GC.

Undetectable circulating tumor DNA confirms the inability of pseudomyxoma peritonei to systemic dissemination.

The study of circulating tumor DNA (ctDNA) plays a pivotal role in advancing precision oncology, providing valuable information for individualized patient care and contributing to the ongoing effort to improve cancer diagnosis, treatment, and management. However, its applicability in pseudomyxoma peritonei (PMP) remains unexplored. In this multicenter retrospective study involving 21 PMP patients, we investigated ctDNA presence in peripheral blood using three distinct methodologies. Despite mucinous tumor tissues exhibiting KRAS and GNAS mutations, ctDNA for these mutations was undetectable in blood samples. In this pilot study, circulating tumor DNA was not detected in blood when the tumor harbored mutations of known significance. In the future, a study with a larger sample size is needed to confirm these findings and to determine whether ctDNA could identify patients at risk for early recurrence and/or systemic metastases.

Utility of Circulating Tumor DNA Assessment in Characterizing Recurrence Sites after Optimal Resection for Metastatic Colorectal Cancer.

BACKGROUND: Plasma circulating tumor DNA (ctDNA) is a promising biomarker for metastatic colorectal cancer (mCRC); however, its role in characterizing recurrence sites after mCRC resection remains poorly understood. This single-institution study investigated the timing of ctDNA detection and its levels in the context of recurrence at different sites after mCRC resection. STUDY DESIGN: Patients who underwent optimal resection of CRC metastases involving the peritoneum, distant lymph nodes, or liver, with serial postoperative tumor-informed ctDNA assessments (Signatera) were included. Recurrence sites, as defined by surveillance imaging or laparoscopy, were categorized as peritoneal-only and other distant sites (liver, lung, lymph nodes, or body wall). RESULTS: Among the 31 included patients, ctDNA was detected in all 26 (83.4%) patients with postoperative recurrence and was persistently undetectable in 5 patients who did not experience recurrence. At 3 months postsurgery, ctDNA was detected in 2 (25%) of 8 patients with peritoneal-only recurrence and 17 (94.4%) of 18 patients with distant recurrence (p < 0.001). Beyond 3 months, ctDNA was detected in the remaining 6 patients with peritoneal-only disease and 1 patient with distant disease. ctDNA detection preceded the clinical diagnosis of recurrence by a median of 9 weeks in both groups. At recurrence, peritoneal-only recurrent cases exhibited lower ctDNA levels (median 0.4 mean tumor molecules/mL, interquartile range 0.1 to 0.8) compared with distant recurrence (median 5.5 mean tumor molecules/mL, interquartile range 0.8 to 33.3, p = 0.004). CONCLUSIONS: Peritoneal-only recurrence was associated with delayed ctDNA detection and low levels of ctDNA after optimal resection for mCRC. ctDNA testing may effectively characterize recurrence sites and may help guide subsequent treatments specific to the disease sites involved.

Levels of CEA and Ca 19 - 9 in the sera and peritoneal cavity in patients with gastric and pancreatic cancers / Níveis de CEA e Ca 19 - 9 em soro e cavidade peritoneal em pacientes com câncer do estômago e pâncreas

PURPOSE: Tumor markers are substances found in blood and other biological fluids if tumor is present in the body. They can be produced by tumor itself or can be results of cancer - body relation. They may be used in the follow-up of cancer patients to identify tumor recurrence. Pre-treatment levels have prognostic tool and could signalize persistence of minimal residual disease despite radical surgery. METHODS: We operated on 52 patients with upper GI malignancy (32 with gastric cancer and 20 with pancreatic cancer). Blood samples were taken before surgery and peritoneal samples immediately after laparotomy before any manipulation with tumor. All samples were examined by standard biochemical technique and the level was compared with a stage of the disease. RESULTS: Patients suffering from gastric carcinoma of stage I and II had higher level of both markers in sera then in the peritoneal cavity, however most of them were within physiological range. Patients in stage III and IV had average marker levels in the peritoneal cavity higher than in sera. Number of positive findings was increasing according to the stage of the disease. The peritoneal levels of both markers varied extremely in higher stages. In patients suffering from pancreatic carcinoma the CEA levels both in sera and peritoneal cavity were parallel but peritoneal levels were slightly higher in stages III and IV. Ca 19 - 9 was more sensitive for pancreatic cancer. The percentage of positive findings was higher in sera but the level of Ca 19 - 9 was higher in the peritoneal cavity. The number of positive findings again correlated with the stage of the disease. CONCLUSIONS: Levels of tumor markers in sera could signalize inoperability of tumor (Ca 19 - 9 in cases of pancreatic carcinoma); peritoneal levels could predict R1 resection especially in gastric cancer patients and risk of early peritoneal recurrence of the disease. Difference between the levels in the peritoneum and sera may signalize the route of dissemination (hematogenous and intraperitoneal).

OBJETIVO: Os marcadores tumorais são substâncias encontradas no sangue e outros fluidos biológicos em pacientes com doenças oncológicas. São produzidos pelo próprio tumor ou ser resultado da interação entre o tumor e o organismo. Podem ser usados no seguimento de pacientes com câncer para identificar recidiva tumoral. Os níveis pré-tratamento têm valor prognóstico e podem sinalizar persistência de doença residual mínima após cirurgia radical.. MÉTODOS: Foram operados 52 pacientes com tumores do trato gastroinstestinal superior (32 com câncer do estômago e 20 do pâncreas). Amostras sanguineas foram colhidas no préoperatório e amostras peritoneais imediatamente após a laparotomia, antes de qualquer manipulação do tumor. Todas as amostras foram examinadas bioquímicamente e os resultados foram comparados entre si e em face ao progresso da doença. RESULTADOS: Os pacientes com câncer de estômago nos estadios I e II apresentaram níveis sanguineos mais elevados de ambos os marcadores tumorais do que no peritônio, mas a maioria dos valores encontrava-se dentro dos limites fisiológicos. Já nos estadios III e IV os níveis dos marcadores tumorais foram mais elevados no peritônio do que no sangue. O número de exames positivos aumentou de acordo com o estadio da doença. Nos estádios avançados, observou-se elevada variabilidade nos níveis de ambos os marcadores analisados no peritônio. Os doentes com carcinoma de pâncreas tiveram níveis de CEA semelhantes no sangue e no peritônio, mas os níveis peritoneais foram ligeiramente mais elevados nos estadios III e IV. Ca 19 - 9 foi muito mais sensível para o câncer do pâncreas. A porcentagem de exames positivos foi mais elevada no sangue, mas o níveis do Ca19-9 foram mais elevados no peritônio.A porcentagem de exames positivos também teve correlação com o estadio da doença. CONCLUSÕES: Os níveis de marcadores tumorais no sangue podem indicar inoperabilidade do tumor. No peritônio podem indicar o tipo de ressecção, especialmente nos doentes com câncer gástrico, e o risco de recidiva peritoneal precoce. A diferença entre os níveis no peritônio e sangue podem sinalizar a via de disseminação, hematogênica ou intra-peritoneal.