Assessment of the Diagnostic Efficiency of a Liquid Biopsy Assay for Early Detection of Gastric Cancer.

Importance: Noninvasive detection of early-stage disease is a key strategy for reducing gastric cancer (GC)-associated patient mortality. Objective: To establish a novel, noninvasive, microRNA (miRNA)-based signature for the early detection of GC using a comprehensive biomarker discovery approach with retrospective and prospective validation. Design, Setting, and Participants: This diagnostic study was conducted in 4 phases using publicly available genome sequences and tissue samples from patients at an academic medical center in Japan, and validated with retrospective multicenter cohorts of patients with GC. Three tissue miRNA data sets were used to identify a miRNA signature that discriminated GC vs normal tissues. The robustness of this signature was assessed in serum from 2 retrospective cohorts of patients with GC. A risk-scoring model was derived, then the performance of the miRNA signature was evaluated in a prospective cohort of patients with GC. The robustness of the miRNA signature was compared with current blood-based markers, and a cost-effectiveness analysis of the miRNA signature against the current practice of endoscopy was performed. All clinical samples used for this study were collected and data analyzed between April 1997 and March 2018. Main Outcomes and Measures: Assessment of diagnostic efficiency on the basis of area under the curve (AUC), specificity, and sensitivity. Results: The data sets for the genome-wide expression profiling analysis stage included 598 total patient samples (284 [55.4%] from men; mean [SE] patient age, 65.7 [0.5] years). The resulting 10-miRNA signature was validated in 2 retrospective GC serum cohorts (586 patients; 348 [59.4%] men, mean [SE] age, 66.0 [0.7] years), which led to the establishment of a 5-miRNA signature (AUC, 0.90; 95% CI, 0.85-0.94) that also exhibited high levels of diagnostic performance in patients with stage I disease (AUC, 0.89; 95% CI, 0.83-0.94). A risk-scoring model was derived and the assay was optimized to a minimal number of miRNAs. The performance of the resulting 3-miRNA signature was then validated in a prospective cohort of patients with GC (349 patients; 124 [70.5%] men, median [range] age, 66.0 [0.66] years). The final 3-miRNA signature (miR-18a, miR-181b, and miR-335) exhibited high diagnostic accuracy in all stages of patients (AUC, 0.86; 95% CI 0.83-0.90), including in patients with stage I disease (AUC, 0.85; 95% CI, 0.79-0.91). Furthermore, this miRNA signature was superior to currently used blood markers and outperformed the endoscopic screening in a cost-effectiveness analysis (incremental cost-effectiveness ratio, CNY ¥16162.5 per quality-adjusted life-year [USD $2304.80 per quality-adjusted life-year]). Conclusions and Relevance: These results suggest the potential clinical significance of the 3-miRNA signature as a noninvasive, cost-effective, and facile assay for the early detection of GC.

Urban-rural disparity in colorectal cancer incidence and increasing trend in relation to socioeconomic development and urbanization in China.

Objective To study urban-rural disparity in colorectal cancer incidence and the increasing trend in relation to rapid socioeconomic development and urbanization in China. Methods We compared the age-standardized incidence rates (ASRs) of colorectal cancer between rural and urban areas in China in 2012 and analyzed the trend in Shexian County for 2000-2015 using population-based tumor registration data collected in Shijiazhuang city (2012) and Shexian County (2000-2015). Results The ASRs of colorectal cancer in Shijiazhuang (urban) were considerably higher than in Shexian (rural) in both men (22.8 vs. 11.9/100,000) and women (15.0 vs. 9.3/100,000). The difference was similar to that between countries with high and medium human development indices according to GLOBOCAN 2012. In trend analysis, the biennial ASR in Shexian increased from 6.6 in 2000-2001 to 15.9/100,000 in 2014-2015 in men (averaged biennial percent change (ABPC) = +6.0%), and from 4.0 to 11.7/100,000 in women (ABPC=+5.5%). Conclusions The incidence of colorectal cancer in China is rising in parallel with socioeconomic development and urbanization. Integrated efforts should be made to reduce the incidences of overweight and obesity in society to help prevent this increase.

Urban-Rural Disparity in Helicobacter Pylori Infection-Related Upper Gastrointestinal Cancer in China and the Decreasing Trend in Parallel with Socioeconomic Development and Urbanization in an Endemic Area.

BACKGROUND: Globally China has the largest urban-rural disparity in socioeconomic development, and the urban-rural difference in upper gastrointestinal cancer (UGIC) is similar to the difference between developed and developing countries. OBJECTIVES: To describe urban-rural disparity in UGIC and to emphasize prevention by socioeconomic development and urbanization in China. METHODS: Age-standardized incidence rates (ASRs) of cancers in 2012 were compared between urban Shijiazhuang city and rural Shexian County, and trends from 2000-2015 in Shexian County were analyzed. FINDINGS: Compared with urban Shijiazhuang city, the ASR of gastroesophageal cancers in rural Shexian County was 5.3 times higher in men (234.1 vs 44.2/100,000, P < .01) and 9.1 times higher in women (107.7 vs 11.8/100,000, P < .01). This rural-urban disparity in UGIC is associated with differences in socioeconomic development in annual gross domestic product (GDP) per capita of US$2700 vs US$6965, in urbanization rate of 48% vs 100%, and in adult Helicobacter pylori infection prevalence of 75% vs 50%. From 2000-2015, the GDP per capita in Shexian County increased from US$860 to US$3000, urbanization rate increased from 22.4% to 54.8%, and prevalence of H pylori infection among 3- to 10-year-old children decreased from 60% to 46.1% (P < .01). Meanwhile, the biennial ASR of esophagogastric cancer decreased 42% in men, from 313.5 to 182.1 per 100,000 (P < .01), and 57% in women, from 188.6 to 80.4 per 100,000 (P = .00). However, lung, colorectal, and gallbladder cancers and leukemia in both sexes and breast, ovary, thyroid, and kidney cancer in women increased significantly. Despite this offset, ASR of all cancers combined decreased 25% in men (from 378.2 to 283.0/100,000, P = .00) and 19% in women (from 238.5 to 193.6/100,000, P = .00). CONCLUSIONS: Urban-rural disparity in UGIC is related to inequity in socioeconomic development. Economic growth and urbanization is effective for prevention in endemic regions in China and should be a policy priority.