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A Novel Four-Gene Score to Predict Pathologically Complete (R0) Resection and Survival in Pancreatic Cancer.

ABSTRACT: Pathologically complete (R0) resection is essential for prolonged survival in pancreatic cancer. Survival depends not only on surgical technique, but also on cancer biology. A biomarker to predict survival is a critical need in pancreatic treatment. We hypothesized that this 4-gene score, which was reported to reflect cell proliferation, is a translatable predictive biomarker for pancreatic cancer. A total of 954 pancreatic cancer patients from multiple cohorts were analyzed and validated. Pancreatic cancer had the 10th highest median score of 32 cancers in The Cancer Genome Atlas (TCGA) cohort. The four-gene score significantly correlated with pathological grade and MKI67 expression. The high four-gene score enriched cell proliferation-related and cancer aggressiveness-related gene sets. The high score was associated with activation of KRAS, p53, transforming growth factor (TGF)-?, and E2F pathways, and with high alteration rate of KRAS and CDKN2A genes. The high score was also significantly associated with reduced CD8⁺ T cell infiltration of tumors, but with high levels of interferon-? and cytolytic activity in tumors. The four-gene score correlated with the area under the curve of irinotecan and sorafenib in primary pancreatic cancer, and with paclitaxel and doxorubicin in metastatic pancreatic cancer. The high four-gene score was associated with significantly fewer R0 resections and worse survival. The novelty of the study is in the application of the four-gene score to pancreatic cancer, rather than the bioinformatics technique itself. Future analyses of inoperable lesions are expected to clarify the utility of our score as a predictive biomarker of systemic treatments.

SUBMITTER: Oshi M

PROVIDER: S-EPMC7761977 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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A Novel Four-Gene Score to Predict Pathologically Complete (R0) Resection and Survival in Pancreatic Cancer.

Oshi Masanori M Tokumaru Yoshihisa Y Patel Ankit A Yan Li L Matsuyama Ryusei R Endo Itaru I Katz Matthew H G MHG Takabe Kazuaki K

Cancers 20201204 12

Pathologically complete (R0) resection is essential for prolonged survival in pancreatic cancer. Survival depends not only on surgical technique, but also on cancer biology. A biomarker to predict survival is a critical need in pancreatic treatment. We hypothesized that this 4-gene score, which was reported to reflect cell proliferation, is a translatable predictive biomarker for pancreatic cancer. A total of 954 pancreatic cancer patients from multiple cohorts were analyzed and validated. Pancr ...[more]

PMID: 33291601

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Project description:Background:To assess the ability of preoperative positron emission tomography/computed tomography (PET/CT) scans to predict postoperative residual disease in advanced epithelial ovarian cancer (AEOC). Methods:Thirty-one women with suspected AEOC were enrolled in our prospective study before surgery from July 2016 to December 2017. Complete resection was determined as no residual disease (R0) after surgery. A PET/CT scan was obtained within 2 weeks before surgery in our hospital. The PET score was the sum of each score of the radiological criteria from Suidan's model. The correlations between the PET score and tumor burden and surgical complexity were evaluated by Pearson correlation analysis. T-test or Fisher's exact test was used to compare differences in the variables between the complete and incomplete resection groups. Receiver operating characteristic (ROC) curve analysis was performed to assess the accuracy of the PET score for predicting complete postoperative resection. Results:The median [range] of PET score was 2 [0-8], and the PET score in 20 (65%) patients was less than 3. Complete resection was achieved in 11 (35.5%) patients after surgery, including 10 (90.91%) with low PET scores and only 1 (9.09%) with a high score. The PET score had a significant positive correlation with tumor burden [Eisenkop: r=0.603, P<0.001; peritoneal cancer index (PCI): r=0.522, P=0.003] but not with surgery complexity (Aletti: r=0.291, P=0.113). Patients with lower PET scores (P=0.046) and tumor burdens (Eisenkop: P=0.013; PCI: P=0.012) had higher rates of complete resection. The PET score and tumor burden were effective for predicting complete resection. The AUCPET, AUCEisenkop, and AUCPCI were 0.797 (95% CI: 0.633-0.961, P=0.01), 0.847 (95% CI: 0.707-0.988, P=0.003), and 0.811 (95% CI: 0.653-0.969, P=0.007), respectively. However, surgery complexity was not useful for assessing complete resection. Conclusions:The preoperative PET score can noninvasively reflect tumor burden and helps predict complete resection after surgery in AEOC patients.

Project description:BackgroundPrevious studies have shown that the all-cause mortality and non-colorectal cancer mortality of patients with fecal occult blood test (FOBT) positivity are significantly increased, implying that FOBT results may have more prognostic value.MethodsRetrospective analysis was performed for gastric cancer (GC) patients who underwent R0 gastrectomy from July 2007 to July 2014 at our hospital. Propensity score matching (PSM) was used to reduce confounding bias and a computerized technique for the nearest available score matching without replacement was applied. The cumulative survival rate was calculated using the Kaplan-Meier method and a log-rank test. Cox proportional hazards regression and logistic regression was used to determine the independent prognostic factors associated with survival and postoperative complications, respectively. The expression level of tumor-associated macrophages (TAMs) and proinflammatory cytokines (TNF-α, IL-6) were evaluated by immunohistochemical (IHC).ResultsA total of 3,003 patients were included and 246 patients (8.2%) were in preoperative FOBT positive status. There was no significant difference in demographic data between preoperative FOBT positive and negative group after a 1:4 PSM. The overall postoperative complications, major complications, and anastomotic leakage were significantly higher in the preoperative FOBT-positive group than in the preoperative FOBT-negative group. Moreover, preoperative FOBT-positivity was an independent risk factor for 5-year overall survival (OS) (HR: 1.32, p = 0.005). For stage II/III patients, the postoperative adjuvant chemotherapy (PAC) benefit was found in preoperative FOBT-negative group (5-year OS: 49.9 vs. 36.8%, p = 0.001), whereas the PAC benefit was lost in preoperative FOBT-positive groups (5-year OS: 40.8 vs. 37.7% p = 0.896). Finally, IHC found that preoperative FOBT-positivity in patients was significantly associated with higher TAMs infiltration and higher expression of IL-6 and TNF-α in tumor tissues than in the preoperative FOBT-negative group.ConclusionAs a simple and low-cost method, preoperative FOBT results can predict both complications and survival after R0 gastrectomy for GC. More importantly, stage II/III GC patients with FOBT-positive seem not benefit from PAC alone. Further exploration is warranted.

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A Novel Four-Gene Score to Predict Pathologically Complete (R0) Resection and Survival in Pancreatic Cancer.

Publications

A Novel Four-Gene Score to Predict Pathologically Complete (R0) Resection and Survival in Pancreatic Cancer.

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