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Scent test using Caenorhabditis elegans to screen for early-stage pancreatic cancer.

ABSTRACT: Although early detection and diagnosis are indispensable for improving the prognosis of patients with pancreatic cancer, both have yet to be achieved. Except for pancreatic cancer, other cancers have already been screened through scent tests using animals or microorganisms, including Caenorhabditis elegans. While such a method may greatly improve the prognosis of pancreatic cancer, no studies have investigated the same, mainly given the difficulty of collecting suitable samples from patients with early-stage pancreatic cancer. In this study, we organized a nationwide study group comprising high-volume centers throughout Japan to collect patients with very-early-stage pancreatic cancer (stage 0 or IA). We initially performed an open-label study involving 83 cases (stage 0-IV), with subsequent results showing significant differences after surgical removal in stage 0-IA (×10 dilution: p < 0.001; ×100 dilution: p < 0.001). Thereafter, a blinded study on 28 cases (11 patients with stage 0 or IA disease and 17 healthy volunteers) was conducted by comparing very-early-stage pancreatic cancer patients with healthy volunteers to determine whether C. elegans could detect the scent of cancer for the diagnosis of early-stage pancreatic cancer. Preoperative urine samples had a significantly higher chemotaxis index compared to postoperative samples in patients with pancreatic cancer [×10 dilution: p < 0.001, area under the receiver operating characteristic curve (AUC) = 0.845; ×100 dilution: p < 0.001, AUC = 0.820] and healthy volunteers (×10 dilution: p = 0.034; ×100 dilution: p = 0.088). Moreover, using the changes in preoperative and postoperative chemotaxis index, this method had a higher sensitivity for detecting early pancreatic cancer compared to existing diagnostic markers. The clinical application C. elegans for the early diagnosis of cancer can certainly be expected in the near future.

SUBMITTER: Asai A

PROVIDER: S-EPMC8378769 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundOne of the most significant challenges in colorectal cancer (CRC) management is the use of compliant early stage population-based diagnostic tests as adjuncts to confirmatory colonoscopy. Despite the near curative nature of early clinical stage surgical resection, mortality remains unacceptably high-as the majority of patients diagnosed by faecal haemoglobin followed by colonoscopy occur at latter stages. Additionally, current population-based screens reliant on fecal occult blood test (FOBT) have low compliance (~ 40%) and tests suffer low sensitivities. Therefore, blood-based diagnostic tests offer survival benefits from their higher compliance (≥ 97%), if they can at least match the sensitivity and specificity of FOBTs. However, discovery of low abundance plasma biomarkers is difficult due to occupancy of a high percentage of proteomic discovery space by many high abundance plasma proteins (e.g., human serum albumin).MethodsA combination of high abundance protein ultradepletion (e.g., MARS-14 and an in-house IgY depletion columns) strategies, extensive peptide fractionation methods (SCX, SAX, High pH and SEC) and SWATH-MS were utilized to uncover protein biomarkers from a cohort of 100 plasma samples (i.e., pools of 20 healthy and 20 stages I-IV CRC plasmas). The differentially expressed proteins were analyzed using ANOVA and pairwise t-tests (p < 0.05; fold-change > 1.5), and further examined with a neural network classification method using in silico augmented 5000 patient datasets.ResultsUltradepletion combined with peptide fractionation allowed for the identification of a total of 513 plasma proteins, 8 of which had not been previously reported in human plasma (based on PeptideAtlas database). SWATH-MS analysis revealed 37 protein biomarker candidates that exhibited differential expression across CRC stages compared to healthy controls. Of those, 7 candidates (CST3, GPX3, CFD, MRC1, COMP, PON1 and ADAMDEC1) were validated using Western blotting and/or ELISA. The neural network classification narrowed down candidate biomarkers to 5 proteins (SAA2, APCS, APOA4, F2 and AMBP) that had maintained accuracy which could discern early (I/II) from late (III/IV) stage CRC.ConclusionMS-based proteomics in combination with ultradepletion strategies have an immense potential of identifying diagnostic protein biosignature.

Project description:ImportanceValue-based care is increasingly important, with rising health care costs and advances in cancer treatment leading to greater survival for patients with cancer. Regionalization of surgical care for pancreatic cancer has been extensively studied as a strategy to improve perioperative outcomes, but investigation of long-term outcomes relative to health care costs (ie, value) is lacking.ObjectiveTo identify patient and hospital characteristics associated with improved overall survival, decreased costs, and greater value among patients with pancreatic cancer undergoing curative resection.Design, setting, and participantsThis retrospective cohort study identified 2786 patients with stages I to II pancreatic cancer who underwent pancreatic resection at 157 hospitals from January 1, 2004, through December 31, 2012. The study used the California Cancer Registry, which collects data from all California residents newly diagnosed with cancer, linked to the Office of Statewide Health Planning and Development database, which collects administrative data from all California licensed hospitals. Data were analyzed from November 11, 2017, through September 4, 2018.ExposuresPancreatic resection at high-volume and/or National Cancer Institute (NCI)-designated cancer centers.Main outcomes and measuresThe primary outcomes were overall survival, surgical hospitalization costs, and value. High value was defined as the fourth quintile or higher for survival and the second quintile or less for costs. Costs were calculated from charges using cost-charge ratios and adjusted for geographic variation and inflation. Multivariable regression models were used to determine factors associated with overall survival, costs, and high value.ResultsAmong the 2786 patients included (1394 [50.0%] male; mean [SD] age, 67.0 [10.7] years), postoperative chemotherapy (adjusted hazard ratio [aHR], 0.71; 95% CI, 0.64-0.79; P < .001) and high-volume centers (aHR, 0.78; 95% CI, 0.61-0.99; P = .04) were associated with greater overall survival. Higher Elixhauser comorbidity index scores (estimate, 0.006; 95% CI, 0.003-0.008), complications (estimate, 0.22; 95% CI, 0.17-0.27), readmissions (estimate, 0.34; 95% CI, 0.29-0.39), and longer lengths of stay (estimate, 0.03; 95% CI, 0.03-0.04) were associated with higher costs (P < .001), whereas postoperative chemotherapy was associated with lower costs (estimate, -0.06; 95% CI, -0.11 to -0.02; P = .006). National Cancer Institute-designated and high-volume centers were not associated with costs. Although grades III and IV tumors (odds ratio [OR], 0.65; 95% CI, 0.39-0.91; P = .001), T3 category disease (OR, 0.71; 95% CI, 0.46-0.95; P = .005), complications (OR, 0.68; 95% CI, 0.49-0.86; P < .001), readmissions (OR, 0.64; 95% CI, 0.44-0.84; P < .001), and length of stay (OR, 0.82; 95% CI, 0.78-0.85; P < .001) were inversely associated with high-value care, NCI designation (OR, 1.07; 95% CI, 0.66-1.49; P = .74) and high-volume centers (OR, 1.08; 95% CI, 0.54-1.61; P = .07) were not.Conclusions and relevanceIn this study, high-value care was associated with important patient characteristics and postoperative outcomes. However, NCI-designated and high-volume centers were not associated with greater value. These data suggest that targeted measures to enhance value may be needed in these centers.

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Scent test using Caenorhabditis elegans to screen for early-stage pancreatic cancer.

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