A Nomogram Model Involving Preoperative Fibrinogen and Prognostic Nutritional Index Score for Predicting Postoperative Outcome in Patients with Gastric Cancer.

BACKGROUND: Inflammation and nutrition play vital roles in the development of gastric cancer (GC). We combined the preoperative fibrinogen with prognostic nutritional index (PNI) to create a novel scoring system named as the fibrinogen and prognostic nutritional index (FPNI) score and establish a more effective model. PATIENTS AND METHODS: A total of 689 patients with gastric adenocarcinoma who underwent gastrectomy from January 2012 to December 2016 were reviewed. We measured correlations between FPNI score and clinicopathological variables and overall survival (OS). A nomogram predicting OS was constructed. Its predictive performance was verified using the concordance index, calibration curves, receiver operating characteristic curves, decision curve analysis and time-dependent receiver operating characteristic analysis. RESULTS: We observed that the FPNI score was an independent predictor of OS in patients with gastric cancer (P < 0.05). A high FPNI score was significantly related to older age at surgery, tumor size ≥4.6 cm, high ASA score, advanced TNM stage and poor outcome (both P < 0.05). And the FPNI score remained an independent indicator at various TNM stages (P < 0.05). Ultimately, the nomogram based on FPNI score, age, tumor size, histological grade and TNM stage showed a better predictive ability than TNM alone. CONCLUSION: The preoperative FPNI score is a novel, simple, and effective predictor of OS in patients with GC. Furthermore, the nomogram involving FPNI score will help clinicians to optimize individualized treatment plans.

A nomogram combining plasma fibrinogen and systemic immune­inflammation index predicts survival in patients with resectable gastric cancer.

Hyperfibrinogenemia and cancer-associated systemic inflammatory response are strongly associated with cancer progression and prognosis. We aimed to develop a novel prognostic score (F-SII score) on the basis of preoperative fibrinogen (F) and systemic immunoinflammatory index (SII), and evaluate its predictive value in patients with resectable gastric cancer (GC). Patients diagnosed with GC between January 2012 and December 2016 were reviewed. The F-SII score was 2 for patients with a high fibrinogen level (≥ 3.37 g/L) and a high SII (≥ 372.8), whereas that for patients with one or neither was 1 or 0, respectively. A high F-SII score was significantly associated with older patient age, a high ASA score, large tumor size, large proportion of perineural invasion, and late TNM stage. Multivariate analysis indicated that the F-SII score, histological grade, and TNM stage were independent factors for overall survival (OS). The Harrell's concordance index (C-index) of a nomogram based on the F-SII score and several clinicopathological manifestations was 0.72, which showed a better predictive ability for OS than the TNM stage alone (0.68). In conclusion, preoperative F-SII may serve as a useful predictive factor for OS and refine outcome prediction for patients with resectable GC combined with traditional clinicopathological analysis.

Intracellular Nampt impairs esophageal squamous cell carcinoma neo-adjuvant chemotherapy response independent of eNampt.

Nampt consists of iNampt and eNampt, might contribute to modulating obesity-related malignancies and impairing response to chemotherapy in a range of cancers. This study explored the role of Nampt and adiposity in the progression and response to neo-adjuvant chemotherapy of esophageal squamous cell carcinoma (ESCC). Patients with ESCC were treated with 2 cycles of neo-adjuvant chemotherapy, then evaluated for surgery. Tumor regression grading (TRG) and prognosis of these patients were collected. Anthropometry was well utilized. Serum eNampt was determined by enzyme-linked immunosorbent assay, iNampt expression in tissues were assessed by PCR, western blot and immunohistochemistry. eNampt in sera elevated significantly in these over-weight or obese patients, and was positively associated with body mass index (BMI), waist circumference, visceral fat area (VFA), subcutaneous fat area (SFA) and total fat area (TFA) (P<0.05). iNampt expression in the mRNA and protein levels were up-regulated in ESCC compared to their adjacent non-tumor specimens (P<0.05). iNampt protein staining revealed mainly in the cytoplasm and nuclei, while it was not related to serum eNampt, BMI, waist circumference, VFA, SFA and TFA (P>0.05). Pre-treatment iNampt, BMI, SFA, TFA and age significantly correlated with neo-adjuvant chemotherapy response, and iNampt expression and age were independent predictors (P<0.05). Pre-treatment iNampt, ypT, ypN, ypTNM stage and TRG were associated with the survival of ESCCs, and ypN stage and TRG were independent prognostic factors (P<0.05). In conclusion, iNampt impaired ESCC response to neo-adjuvant chemotherapy independent of eNampt, targeting iNampt to increase ESCC response to neo-adjuvant chemotherapy would improve the prognosis of ESCCs.

Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway.

Obesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vitro. Diet-induced obese and lean nude mice were inoculated with TE-1 cells, then studied for 4 weeks. Serum glucose, insulin, leptin, and visfatin levels were assayed. Sera of nude mice were obtained and then utilized to culture TE-1. MTT, migration and invasion assays, RT-PCR, and Western blotting were used to analyze endocrine effect of obesity on cell proliferation, migration, invasion, and related genes expression of TE-1. Obese nude mice bore larger tumor xenografts than lean animals, and were hyperglycemic and hyperinsulinemic with an elevated level of leptin and visfatin in sera, and also were accompanied by a fatty liver. As for the subcutaneous tumor xenograft model, tumors were more aggressive in obese nude mice than lean animals. Tumor weight correlated positively with mouse body weight, liver weight of mice, serum glucose, HOMA-IR, leptin, and visfatin. Obesity prompted significant TE-1 cell proliferation, migration, and invasion by endocrine mechanisms and impacted target genes. The expression of AMPK and p-AMPK protein decreased significantly (P < 0.05); MMP9, total YAP, p-YAP, and nonphosphorylated YAP protein increased significantly (P < 0.05) in the cells cultured with conditioned media and xenograft tumor from the obese group; the mRNA expression of AMPK decreased significantly (P < 0.05); YAP and MMP9 mRNA expression increased significantly (P < 0.05) in the cells exposed to conditioned media from the obese group. In conclusion, the altered adipokine milieu and metabolites in the context of obesity may promote ESCC growth in vivo; affect proliferation, migration, and invasion of ESCC cells in vitro; and regulate MMP9 and AMPK-YAP signaling pathway through complex effects including the endocrine effect.