MicroRNA-21 ISH analysis to predict DFS in pancreatic cancer patients undergoing adjuvant gemcitabine after curative surgery.

Abstract

234 Background: Overexpression of microRNA-21(miR-21) in pancreatic cancer has been reported to be associated with tumor cell proliferation, invasion, and also resistance to gemcitabine (GEM) chemotherapy. The aim of this study was to evaluate whether miR-21 expression, determined by microRNA ISH, was associated with clinical outcomes of pancreatic cancer patients who underwent adjuvant gemcitabine chemotherapy after curative surgery. Methods: Expression levels of miR-21 were semi quantitatively analyzed for staining intensity and distribution of positive tumor cells, by microRNA ISH in formalin-fixed paraffin embedded tissue arrays from 41 pancreatic cancer patients who underwent adjuvant GEM chemotherapy after curative resection at Kanagawa Cancer Center. The staining intensity for the miR-21 was assigned a score from 1 to 3 based on staining with1+: weakly, 2+: moderately, and 3+: strongly positive. The percentage of positive tumor cells was scored as follows, 1+: < 50% positive cells, 2+: 50-80% positive cells, and 3+: ³a 81% positive cells. A composite score was obtained by calculating the sum of these two scores. Results: 27 patients were assigned to low miR-21 expression group (score <4) and 14 patients to high miR-21 group (score 4,5,6). High miR-21 expression group had a significantly shorter DFS (P = 0.039, by log-rank test). The median DFS was 9.8 months (95% CI, 6.9-12.6) in the low miR-21 group, and 7.9 months (95% CI, 6.1-9.8) in the high miR-21 group. The median OS was 19.6 months (95% CI, 6.3-32.8) in the low miR-21 group, and 15.1 months (95% CI, 11.7-18.5) in the high miR-21 group, but was not significant. Multivariate analysis including miR-21 expression, microscopic lymphatic invasion and microscopic perineural invasion, indicated that miR-21 expression (p = 0.024) and microscopic lymphatic invasion (p = 0.035) were the independent predictor for DFS. Conclusions: A high level of miR-21 expression in pancreatic cancer was significantly associated with shorter DFS in patients who received adjuvant GEM after curative resection. miR-21 ISH analysis may serve as a significant predictor for GEM resistance in adjuvant setting.

Prognostic nutritional score based on pretreatment lymphocyte, platelet, and prealbumin predicts prognosis in patients with pancreatic cancer

“…Researchers usually assess nutritional status by weight loss, body mass index, albumin, prealbumin, PNI, and Glasgow prognostic score 25–27 . With a relatively short half‐life, prealbumin is a more sensitive biomarker than albumin for assessing the nutritional status 10 .…”

“…Researchers usually assess nutritional status by weight loss, body mass index, albumin, prealbumin, PNI, and Glasgow prognostic score. [25][26][27] With a relatively short half-life, prealbumin is a more sensitive biomarker than albumin for assessing the nutritional status. 10 Prealbumin has been affirmed to be a useful predictor of survival in various malignancies, including esophageal, hepatocellular, and gastric cancers, [14][15][16] however, its prognostic role in PC has not been investigated.…”

Advances in Chemotherapy for Pancreatic Cancer

“…[11] Randomized controlled clinical trials and meta-analyses suggest a significant OS benefit from chemotherapy alone following resection of a pancreatic cancer. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Current standard of care is Gemcitabine alone for 6 months postsurgery given the interpretations from the ESPAC-3 study which showed that though there was not a survival advantage with Gemcitabine compared to 5-FU, toxicities were significantly less with Gemcitabine. [16] Table 1 shows the key studies of adjuvant therapy in pancreatic cancer.…”

“…[2] In advanced disease progress has been made with newer combination regimens with prolongation of survival but it still has not gone beyond a year. [3] Extensive research is ongoing into newer biological agents which are being combined with chemotherapy and markers of drug resistance like human equilibrative nucleoside transporter-1 (hENT1), [4] MMP-7 [5] and micro RNA21 (miR-21) [6] are being looked into so that treatment of each patient can be individualised. This review focuses on the current status of chemotherapy in all settings -neoadjuvant, adjuvant and metastatic for patients with pancreatic cancer.…”