Postoperative serum CA19-9, YKL-40, CRP and IL-6 in combination with CEA as prognostic markers for recurrence and survival in colorectal cancer

Background In colorectal cancer (CRC) patients, guidelines only recommend measurement of preoperative carcinoembryonic antigen (CEA), although postoperative CEA may be more informative. However, the sensitivity of both preoperative and postoperative CEA in identifying relapse is limited. We studied whether CA19-9, YKL-40, C-reactive protein (CRP) and interleukin (IL)-6 add prognostic information combined with postoperative CEA. Material and methods This post-hoc analysis included 147 radically resected stage II (n = 38), III (n = 91) and IV (n = 18) CRC patients treated with adjuvant 5-fluorouracil (5-FU)-based therapy in the phase III LIPSYT study (ISRCTN98405441). We collected postoperative blood samples a median of 48 days after surgery. We analysed relapses, sensitivity, positive predictive value (PPV) and disease-free (DFS) and overall survival (OS) by bootstrap, Kaplan-Meier and adjusted Cox-models in the elevated vs. normal biomarker groups. Results Elevated postoperative CEA associated with impaired DFS (HR 7.23; CI(95%)3.85-13.58), impaired OS (HR 7.16; CI(95%)3.76-13.63), and more relapses (HR 7.9; CI(95%)3.4-18.2); but sensitivity for CEA in finding relapses was only 31% (CI(95%)21-48%). Normal CEA combined with an elevated YKL-40 or elevated CRP showed more relapses (HR for YKL-40 2.13 [CI(95%)1.10-4.13], HR for CRP 3.14 [CI(95%)1.21-8.16]), impaired DFS (HR 2.18 [CI(95%)1.12-4.24] or 3.23 [CI(95%)1.34-7.82]), and impaired OS (2.33 [CI(95%)1.24-4.40] or 2.68 [CI(95%)1.12-6.44]). Elevated CEA combined with a concomitantly elevated CA19-9, YKL-40, CRP or IL-6 showed a respective PPV of 100, 90, 100, and 100%. Conclusion In radically operated stage II to IV CRC patients who received adjuvant 5-FU-based chemotherapy, a postoperatively elevated CEA alone or in combination with CA19-9, YKL-40, CRP, or IL-6, or a normal CEA combined with an elevated YKL-40 or with an elevated CRP, may indicate patients at high risk of relapse.Peer reviewe

Tissue MicroRNA profiles as diagnostic and prognostic biomarkers in patients with resectable pancreatic ductal adenocarcinoma and periampullary cancers

BACKGROUND: The aim of this study was to validate previously described diagnostic and prognostic microRNA expression profiles in tissue samples from patients with pancreatic cancer and other periampullary cancers. METHODS: Expression of 46 selected microRNAs was studied in formalin-fixed paraffin-embedded tissue from patients with resected pancreatic ductal adenocarcinoma (n = 165), ampullary cancer (n=59), duodenal cancer (n = 6), distal common bile duct cancer (n = 21), and gastric cancer (n = 20); chronic pancreatitis (n = 39); and normal pancreas (n = 35). The microRNAs were analyzed by PCR using the Fluidigm platform. RESULTS: Twenty-two microRNAs were significantly differently expressed in patients with pancreatic cancer when compared to healthy controls and chronic pancreatitis patients; 17 miRNAs were upregulated (miR-21-5p, −23a-3p, −31-5p, −34c-5p, −93-3p, −135b-3p, −155-5p, −186-5p, −196b-5p, −203, −205-5p, −210, −222-3p, −451, −492, −614, and miR-622) and 5 were downregulated (miR-122-5p, −130b-3p, −216b, −217, and miR-375). MicroRNAs were grouped into diagnostic indices of varying complexity. Ten microRNAs associated with prognosis were identified (let-7 g, miR-29a-5p, −34a-5p, −125a-3p, −146a-5p, −187, −205-5p, −212-3p, −222-5p, and miR-450b-5p). Prognostic indices based on differences in expression of 2 different microRNAs were constructed for pancreatic and ampullary cancer combined and separately (30, 5, and 21 indices). CONCLUSION: The study confirms that pancreatic cancer tissue has a microRNA expression profile that is different from that of other periampullary cancers, chronic pancreatitis, and normal pancreas. We identified prognostic microRNAs and microRNA indices that were associated with shorter overall survival in patients with radically resected pancreatic cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40364-017-0087-6) contains supplementary material, which is available to authorized users

Plasma YKL-40 is associated with prognosis in patients with metastatic pancreatic cancer receiving immune checkpoint inhibitors in combination with radiotherapy

BackgroundYKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is a secreted glycoprotein produced by various cell types including stromal, immune, and cancer cells. It contributes to cancer progression through tumor-promoting inflammation and has been shown to inhibit the cytotoxicity of T and NK lymphocytes. In vivo studies have demonstrated synergistic anti-cancer effects of blocking YKL-40 in combination with immune checkpoint inhibitors (ICIs). Biomarkers for the prediction of the response to ICIs are highly needed. We investigated the association between plasma YKL-40 and clinical benefit and survival in patients with metastatic pancreatic cancer (mPC) receiving ICIs and stereotactic body radiotherapy (SBRT).MethodsBlood samples were collected from 84 patients with mPC who participated in the randomized phase II CheckPAC study, in which patients received nivolumab with or without ipilimumab combined with a single fraction of SBRT. Plasma YKL-40 was measured using a commercial ELISA kit.ResultsElevated baseline plasma YKL-40 was an independent predictor of shorter overall survival (OS) (HR 2.19, 95% CI 1.21–3.95). A ≥ 40% decrease in plasma YKL-40 during treatment was associated with longer progression-free survival (p = 0.009) and OS (p = 0.0028). There was no correlation between plasma YKL-40 and the tumor burden marker CA19-9 at baseline or during treatment.ConclusionThis study contributes new knowledge regarding YKL-40 as a predictor of clinical benefit from ICIs and radiotherapy. These exploratory results warrant further investigation of YKL-40 as a biomarker for patients treated with immunotherapies.Clinical trial registrationClinicaltrials.gov, identifier NCT02866383

Additional file 1 of Levels of type XVII collagen (BP180) ectodomain are elevated in circulation from patients with multiple cancer types and is prognostic for patients with metastatic colorectal cancer

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