Restricted accessResearch articleFirst published online 2025-08
The Relationship Between Metabolic and Inflammatory Parameters at the Time of Diagnosis and Disease Stage and Prognosis in Patients with Pancreatic Cancer
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive tumor often accompanied by various metabolic abnormalities both before and after clinical diagnosis. Diagnosis at advanced stages significantly increases mortality risk. This study aimed to investigate the potential relationship between metabolic and inflammatory parameters at the time of diagnosis and disease stage, and their impact on prognosis in patients with pancreatic cancer.
Materials and Methods:
A total of 89 patients (43.8% male, 56.2% female) diagnosed with PDAC were included in the retrospective, single-center study. Disease stages at diagnosis that were categorized as stages 1–2 (resectable) and stages 3–4 (locally advanced and metastatic), height, weight, accompanying diseases, body mass index (BMI), inflammatory parameters (C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), and metabolic parameters (glucose, HbA1c %, triglyceride, High-Density Lipoprotein [HDL]-cholesterol, Low-Density Lipoprotein [LDL]-cholesterol) were recorded. These parameters were compared between early and advanced stage patients, and their effect on one-year survival was evaluated.
Results:
The mean age of the patients was 62.7 years; 45.1% of the patients were in stages 1–2, while 48.3% were in stage 4. The one-year overall mortality rate was 32.6%, and the mortality rate was 52.1% in advanced stage (stages 3–4) patients and 9.8% in early stage (stages 1–2) patients. Mean CRP and NLR levels were significantly higher in patients who died compared to those who survived (7.4 vs. 4.4, p = 0.001; p = 0.000, respectively). Mean HDL-cholesterol level was lower in patients who died compared to survivors (34 mg/dL vs. 47.2 mg/dL, p = 0.001). Mean fasting blood glucose and HbA1c levels were higher in patients who died compared to survivors (167 mg/dL vs. 135 mg/dL, 7.5% vs. 6.6%; p = 0.008; p = 0.037, respectively). There were no significant differences in gender, BMI, presence of co-morbidities, triglyceride, or LDL-cholesterol levels between the groups.
Conclusion:
Recognizing clinical biomarkers predicting prognosis in PDAC could significantly contribute to disease management.
SiegelRL, MillerKD, JemalA. Cancer statistics, 2020. CA Cancer J Clin, 2020; 70(1):7–30; doi: 10.3322/caac.21590
4.
JohansenD, StocksT, JonssonH, et al.Metabolic factors and the risk of pancreatic cancer: A prospective analysis of almost 580,000 men and women in the metabolic syndrome and cancer project. Cancer Epidemiol Biomarkers Prev, 2010; 19(9):2307–2317; doi: 10.1158/1055-9965
5.
BracciPM. Obesity and pancreatic cancer: Overview of epidemiologic evidence and biologic mechanisms. Mol Carcinog, 2012; 51(1):53–63; doi: 10.1002/mc.20778
6.
Quoc LamB, ShrivastavaSK, ShrivastavaA, et al.The impact of obesity and diabetes mellitus on pancreatic cancer: Molecular mechanisms and clinical perspectives. J Cell Mol Med, 2020; 24(14):7706–7716; doi: 10.1111/jcmm.15413
7.
BosettiC, RosatoV, LiD, et al.Diabetes, antidiabetic medications, and pancreatic cancer risk: An analysis from the International Pancreatic Cancer Case-Control Consortium. Ann Oncol, 2014; 25(10):2065–2072; doi: 10.1093/annonc/mdu276
8.
DanknerR, BoffettaP, BalicerRD, et al.Time-Dependent risk of cancer after a diabetes diagnosis in a cohort of 2.3 million adults. Am J Epidemiol, 2016; 183(12):1098–1106; doi: 10.1093/aje/kwv290
9.
DouglasJB, SilvermanDT, WeinsteinSJ, et al.Serum C-reactive protein and risk of pancreatic cancer in two nested, case-control studies. Cancer Epidemiol Biomarkers Prev, 2011; 20(2):359–369; doi: 10.1158/1055-9965
10.
YangJJ, HuZG, ShiWX, et al.Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: A meta-analysis. World J Gastroenterol, 2015; 21(9):2807–2815; doi: 10.3748/wjg.v21.i9.28072807.
11.
JeonCY, LiD, ClearyS, et al.The association of recentlydiagnosed diabetes and long-term diabetes with survival in pancreatic cancer patients: A pooled analysis. Pancreas, 2018; 47(3):314–320; doi: 10.1097/MPA.0000000000000989
12.
PangY, KartsonakiC, GuoY, et al.Diabetes, plasma glucose and incidence of pancreatic cancer: A prospective study of 0.5 million Chinese adults and a meta-analysis of 22 cohort studies. Int J Cancer, 2017; 140(8):1781–1788; doi: 10.1002/ijc.30599
13.
MaglianoDJ, DavisWA, ShawJE, et al.Incidence and predictors of all-cause and site-specific cancer in type 2 diabetes: The fremantle diabetes study. Eur J Endocrinol, 2012; 167(4):589–599; doi: 10.1530/EJE-12-0053
14.
ChenY, WuF, SaitoE, et al.Association between type 2 diabetes and risk of cancer mortality: A pooled analysis of over 771,000 individuals in the Asia Cohort Consortium. Diabetologia, 2017; 60(6):1022–1032; doi: 10.1007/s00125-017-4229-z
15.
GantiAK, PottiA, KochM, et al.Predictive value of clinical features at initial presentation in pancreatic adenocarcinoma: A series of 308 cases. Med Oncol, 2002; 19(4):233–237; doi: 10.1385/MO:19:4:233
16.
BenQ, XuM, JiangY, et al.Clinical profiles and long-term outcomes of patients with pancreatic ductal adenocarcinoma and diabetes mellitus. Diabetes Metab Res Rev, 2012; 28(2):169–176; doi: 10.1002/dmrr.1284
17.
ToriolaAT, Stolzenberg-SolomonR, DalidowitzL, et al.Diabetes and pancreatic cancer survival: A prospective cohort-based study. Br J Cancer, 2014; 111(1):181–185.
18.
CannonRM, LeGrandR, ChagparRB, et al.Multi-institutional analysis of pancreatic adenocarcinoma demonstrating the effect of diabetes status on survival after resection. HPB (Oxford), 2012; 14(4):228–235.
19.
ChuCK, MazoAE, GoodmanM, et al.Preoperative diabetes mellitus and long-term survival after resection of pancreatic adenocarcinoma. Ann Surg Oncol, 2010; 17(2):502–513.
20.
WakasugiH, FunakoshiA, IguchiH. Clinical observations of pancreatic diabetes caused by pancreatic carcinoma, and survival period. Int J Clin Oncol, 2001; 6(1):50–54.
21.
YuanC, RubinsonDA, QianZR, et al.Survival among patients with pancreatic cancer and long-standing or recent-onset diabetes mellitus. J Clin Oncol, 2015; 33(1):29–35.
22.
LiD, MaoY, ChangP, et al.Impacts of new-onset and long-term diabetes on clinical outcome of pancreatic cancer. Am J Cancer Res, 2015; 5(10):3260–3269.
23.
PelucchiC, GaleoneC, PoleselJ, et al.Smoking and body mass index and survival in pancreatic cancer patients. Pancreas, 2014; 43(1):47–52.
24.
LingS, BrownK, MikszaJK, et al.Association of type 2 diabetes with cancer: A meta-analysis with bias analysis for unmeasured confounding in 151 cohorts comprising 32 million people. Diabetes Care, 2020; 43(9):2313–2322; doi: 10.2337/dc20-0204
25.
RoyA, SahooJ, KamalanathanS, et al.Diabetes and pancreatic cancer: Exploring the two-way traffic. World J Gastroenterol, 2021; 27(30):4939–4962; doi: 10.3748/wjg.v27.i30.4939
26.
GiovannucciE, HarlanDM, ArcherMC, et al.Diabetes and cancer: A consensus report. CA Cancer J Clin, 2010; 60(4):207–221; doi: 10.3322/caac.20078
27.
García-JiménezC, Gutiérrez-SalmerónM, Chocarro-CalvoA, et al.From obesity to diabetes and cancer: Epidemiological links and role of therapies. Br J Cancer, 2016; 114(7):716–722; doi: 10.1038/bjc.2016.37Mar 29
28.
SunamiY, RebeloA, KleeffJ. Lipid metabolism and lipid droplets in pancreatic cancer and stellate cells. Cancers (Basel), 2017; 10(1):3; doi: 10.3390/cancers1001000323
29.
PirhonenJ, SzkalisityÁ, HagströmJ, et al.Lipid metabolic reprogramming extends beyond histologic tumor demarcations in operable human pancreatic cancer. Cancer Res, 2022; 82(21):3932–3949; doi: 10.1158/0008-5472.CAN-22-0396
30.
SouchekJJ, BaineMJ, LinC, et al.Unbiased analysis of pancreatic cancer radiation resistance reveals cholesterol biosynthesis as a novel target for radiosensitisation. Br J Cancer, 2014; 111(6):1139–1149; doi: 10.1038/bjc.2014.385
31.
GuillaumondF, BidautG, OuaissiM, et al.Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma. Proc Natl Acad Sci U S A, 2015; 112(8):2473–2478; doi: 10.1073/pnas.1421601112
32.
JafriH, Alsheikh-AliAA, KarasRH. Baseline and on-treatment high-density lipoprotein cholesterol and the risk of cancer in randomized controlled trials of lipid-altering therapy. J Am Coll Cardiol, 2010; 55(25):2846–2854; doi: 10.1016/j.jacc.2009.12.069
33.
OberleR, KuhrerK, OsterreicherT, et al.The HDL particle composition determines its antitumor activity in pancreatic cancer. Life Sci Alliance, 2022; 5(9):e202101317; doi: 10.26508/lsa.202101317May 16
34.
JuarezD, FrumanDA. Targeting the mevalonate pathway in cancer. Trends Cancer, 2021; 7(6):525–540; doi: 10.1016/j.trecan.2020.11.008
35.
Di BelloE, ZwergelC, MaiA, et al.The Innovative Potential of Statins in Cancer: New Targets for New Therapies. Front Chem, 2020; 8:516; doi: 10.3389/fchem.2020.005162020
36.
PadoanA, PlebaniM, BassoD. Inflammation and pancreatic cancer: Focus on metabolism, cytokines, and ımmunity. Int J Mol Sci, 2019; 20(3):676; doi: 10.3390/ijms20030676
37.
SzkanderaJ, StotzM, AbsengerG, et al.Validation of C-reactive protein levels as a prognostic indicator for survival in a large cohort of pancreatic cancer patients. Br J Cancer, 2014; 110(1):183–188; doi: 10.1038/bjc.2013.701
38.
LiuZ, JinK, GuoM, et al.Prognostic value of the CRP/Alb Ratio, a novel ınflammation-based score in pancreatic cancer. Ann Surg Oncol, 2017; 24(2):561–568; doi: 10.1245/s10434-016-5579-3
39.
MroczkoB, GroblewskaM, GrykoM, et al.Diagnostic usefulness of serum interleukin 6 (IL-6) and C-reactive protein (CRP) in the differentiation between pancreatic cancer and chronic pancreatitis. J Clin Lab Anal, 2010; 24(4):256–261; doi: 10.1002/jcla.20395
40.
YamadaS, FujiiT, YabusakiN, et al.Clinical ımplication of ınflammation-based prognostic score in pancreatic cancer: Glasgow prognostic score ıs the most reliable parameter. Medicine (Baltimore), 2016; 95(18):e3582; doi: 10.1097/MD.0000000000003582May
41.
LesinaM, KurkowskiMU, LudesK, et al.Stat3/Socs3 activation by IL-6 transsignaling promotes progression of pancreatic intraepithelial neoplasia and development of pancreatic cancer. Cancer Cell, 2011; 19(4):456–469; doi: 10.1016/j.ccr.2011.03.009
42.
YuanC, Morales-OyarvideV, KhalafN, et al.Prediagnostic ınflammation and pancreatic cancer survival. J Natl Cancer Inst, 2021; 113(9):1186–1193; doi: 10.1093/jnci/djab040Sep 4
43.
KuwadaY, SasakiT, MorinakaK, et al.Potential involvement of IL-8 and its receptors in the invasiveness of pancreatic cancer cells. Int J Oncol, 2003; 22(4):765–771.
44.
FogarP, SpertiC, BassoD, et al.Decreased Total Lymphocyte counts in pancreatic cancer: an ındex of adverse outcome. Pancreas, 2006; 32(1):22–28; doi: 10.1097/01.mpa.0000188305.90290.50
45.
PointerDT, RoifeD, PowersBD, et al.Neutrophil to lymphocyte ratio, not platelet to lymphocyte or lymphocyte to monocyte ratio, is predictive of patient survival after resection of early-stage pancreatic ductal adenocarcinoma. BMC Cancer, 2020; 20(1):750; doi: 10.1186/s12885-020-07182-9
46.
AquilaniR, BrugnatelliS, MaestriR, et al.Peripheral blood lymphocyte percentage may predict chemotolerance and survival in patients with advanced pancreatic cancer. Association between adaptive ımmunity and nutritional state. Curr Oncol, 2021; 28(5):3280–3296; doi: 10.3390/curroncol28050285
