Detection of Pancreatic Cancer Biomarkers Using Mass Spectrometry

Background Pancreatic cancer is the fourth leading cause of cancer-related deaths. Therefore, in order to improve survival rates, the development of biomarkers for early diagnosis is crucial. Recently, diabetes has been associated with an increased risk of pancreatic cancer. The aims of this study were to search for novel serum biomarkers that could be used for early diagnosis of pancreatic cancer and to identify whether diabetes was a risk factor for this disease. Methods Blood samples were collected from 25 patients with diabetes (control) and 93 patients with pancreatic cancer (including 53 patients with diabetes), and analyzed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/MS). We performed preprocessing, and various classification methods with imputation were used to replace the missing values. To validate the selection of biomarkers identified in pancreatic cancer patients, we measured biomarker intensity in pancreatic cancer patients with diabetes following surgical resection and compared our results with those from control (diabetes-only) patients. Results By using various classification methods, we identified the commonly splitting protein peaks as m/z 1,465, 1,206, and 1,020. In the follow-up study, in which we assessed biomarkers in pancreatic cancer patients with diabetes after surgical resection, we found that the intensities of m/z at 1,465, 1,206, and 1,020 became comparable with those of diabetes-only patients.

Download Full-text

Effect of body mass index (BMI) on outcomes after surgical resection and adjuvant therapy for pancreatic cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.185 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 185-185

Author(s):

M. R. Khawaja ◽

N. Zyromski ◽

M. Yu ◽

H. R. Cardenes ◽

C. M. Schmidt ◽

...

Keyword(s):

Pancreatic Cancer ◽

Adjuvant Therapy ◽

Cancer Patients ◽

Surgical Resection ◽

Survival Rates ◽

Disease Free Survival ◽

University Hospital ◽

Rank Test ◽

Kaplan Meier ◽

Significant Difference

185 Background: Obesity is one of the factors commonly associated with pancreatic cancer risk, but its prognostic role for survival is debatable. This study aimed to determine the role of BMI in treatment outcomes of pancreatic cancer patients (pts) undergoing surgical resection followed by adjuvant therapy. Methods: We retrospectively reviewed 165 consecutive pts with pancreatic cancer undergoing pancreaticoduodenectomy at Indiana University Hospital between 2004 and 2008. Fifty-three pts who received adjuvant treatment [gemcitabine alone (C-group): n=19; gemcitabine + radiotherapy (CRT-group): n=34] at our institution were included in the analysis. The Kaplan-Meier method was used to estimate the disease-free survival (DFS) and overall survival (OS); log-rank test was used to compare these outcomes between BMI groups (normal 18.5-24.99 kg/m2 vs. overweight/obese ≥ 25 kg/m2). Results: The sample comprised 53 pts (28 males; median age 62 yrs) with a median follow-up of 18.6 months (mos). Thirty pts (56.6%) had their BMIs recorded before the date of surgery, and 23 pts prior to starting adjuvant therapy. Two (3.8%) pts were underweight, 21 (39.6%) had a normal BMI and 30 (56.6%) were overweight/obese. There was no statistically significant difference in the median DFS of obese/overweight and normal BMI pts irrespective of adjuvant therapy (C or CRT) (14.47 vs. 11.80 mos; p= 0.111). Obese/overweight pts had a better median OS [25.2 vs. 14.6 mos; p=0.045 overall (25.7 vs. 16.9 mos; p= 0.143 for the CRT-group and 17.3 vs. 13.4 mos; p= 0.050 for the C-group)], 1-year survival [96.7% vs. 61.9%; p < 0.0001 overall (95% vs. 64.3%; p= 0.001 for the CRT-group, and 90% vs. 57.1%; p=0.016 with C)], and 2-year survival [52.6% vs. 25.4%; p < 0.0001 overall (60.0% vs. 30.0%; p=0.0001 for the CRT-group and 37.5% vs. 14.3%; p=0.0002 for the C-group)] than patients with normal BMI. Conclusions: In our experience, overweight/obese pts undergoing surgery followed by adjuvant therapy have better survival rates than patients with normal BMI. [Table: see text] No significant financial relationships to disclose.

Download Full-text

Differential secretome of pancreatic cancer cells in serum-containing conditioned medium reveals CCT8 as a new biomarker of pancreatic cancer invasion and metastasis

Cancer Cell International ◽

10.1186/s12935-019-0980-1 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Peng Liu ◽

Lingming Kong ◽

Haoyi Jin ◽

Yunhao Wu ◽

Xiaodong Tan ◽

...

Keyword(s):

Mass Spectrometry ◽

Pancreatic Cancer ◽

Early Diagnosis ◽

Western Blot ◽

Cancer Patients ◽

Cancer Cell ◽

Liquid Biopsy ◽

Pancreatic Cancer Cell ◽

Secreted Proteins ◽

Invasion And Metastasis

Abstract Background Pancreatic cancer is a malignancy with a very poor prognosis. The emergence of liquid biopsy is expected to achieve accurate early diagnosis through detection of tumor-derived secreted proteins in the blood. Early diagnosis and treatment of pancreatic cancer could help to improve prognosis. Methods The pretreatment approach of samples can have a major effect on downstream analysis. In this study, we used a pair of homologous pancreatic cancer cell supernatants with different capacities for invasion and metastasis to examine secreted proteins in the conditioned media without the removal of fetal bovine serum, namely through size exclusion chromatography combined with high-abundance protein affinity chromatography to enrich low-concentration protein, followed by mass spectrometry using triple dimethyl labeling. Identification of proteins was performed using an online public database and western blot. Results Mass spectrometry data revealed 77 proteins with quantitative properties, of which 12 proteins had over a 1.5-fold difference (in the supernatant of the highly invasive pancreatic cancer cell line PC-1.0, the expression of 8 proteins were increased and the expression of 4 proteins were decreased). Bioinformatics analysis results showed that CCT8, CTSL, SAA1, IGF2 are secreted via the exosome pathway. According to the literature, with the exception of CCT8, the other three proteins can be detected in blood samples of pancreatic cancer patients, and they can be used as prognostic markers. Western blot results were used to validate consistency with MS results. Conclusion This study found that CCT8 can be used as a liquid biopsy marker to assess the prognosis of pancreatic cancer patients.

Download Full-text

Microbial Associations with Pancreatic Cancer: A New Frontier in Biomarkers

Cancers ◽

10.3390/cancers13153784 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3784

Author(s):

Mark Stasiewicz ◽

Marek Kwaśniewski ◽

Tomasz M. Karpiński

Keyword(s):

Pancreatic Cancer ◽

Helicobacter Pylori ◽

Survival Rates ◽

Health Concern ◽

Current State ◽

Increased Risk ◽

Microbial Biomarkers ◽

New Frontier ◽

Microbial Associations ◽

Fungal Genus

Pancreatic cancer (PC) remains a global health concern with high mortality and is expected to increase as a proportion of overall cancer cases in the coming years. Most patients are diagnosed at a late stage of disease progression, which contributes to the extremely low 5-year survival rates. Presently, screening for PC remains costly and time consuming, precluding the use of widespread testing. Biomarkers have been explored as an option by which to ameliorate this situation. The authors conducted a search of available literature on PubMed to present the current state of understanding as it pertains to the use of microbial biomarkers and their associations with PC. Carriage of certain bacteria in the oral cavity (e.g., Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Streptococcus sp.), gut (e.g., Helicobacter pylori, Synergistetes, Proteobacteria), and pancreas (e.g., Fusobacterium sp., Enterobacteriaceae, Pseudomonadaceae) has been associated with an increased risk of developing PC. Additionally, the fungal genus Malassezia has likewise been associated with PC development. This review further outlines potential oncogenic mechanisms involved in the microbial-associated development of PC.

Download Full-text

Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging

PLoS Medicine ◽

10.1371/journal.pmed.1002108 ◽

2016 ◽

Vol 13 (8) ◽

pp. e1002108 ◽

Cited By ~ 41

Author(s):

Livia S. Eberlin ◽

Katherine Margulis ◽

Ivette Planell-Mendez ◽

Richard N. Zare ◽

Robert Tibshirani ◽

...

Keyword(s):

Mass Spectrometry ◽

Pancreatic Cancer ◽

Surgical Resection ◽

Mass Spectrometry Imaging ◽

Resection Margins ◽

Molecular Assessment

Download Full-text

Metformin in diabetic pancreatic cancer patients: Benefit or not—Multicenter experience.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e15110 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e15110-e15110 ◽

Cited By ~ 1

Author(s):

Onur Esbah ◽

Berna Oksuzoglu ◽

Tulay Eren ◽

Kaan Helvaci ◽

Tunc Guler ◽

...

Keyword(s):

Diabetes Mellitus ◽

Pancreatic Cancer ◽

Cancer Patients ◽

Pancreas Cancer ◽

Tumour Size ◽

Pancreas Carcinoma ◽

Number Of Patients ◽

Stage 4 ◽

Patients With Diabetes ◽

Stage 1

e15110 Background: Risk factors for the pancreatic cancer are cigarette smoking, obesity, family history, chronic pancreatitis and type 2 diabetes mellitus. Diabetes mellitus is associated with 2-3 fold increase in the risk of pancreas cancer development. Down-regulation of mTOR pathway which begins with the insulin signaling is the possible protective effect of metformin in the oncogenesis of pancreatic cancer. In this study, we aimed to evaluate whether the use of metformin in diabetic pancreas cancer patients has an advantage or not. Methods: The data of 467 patients with the diagnosis of pancreas cancer in from 2003 to 2012 were analyzed, retrospectively. Results: Four hundred and sixty seven patients with the median age of 62 (20-85) were reviewed Median tumour size was 42 mm (14-145 mm). According to 2010 TNM staging, 23 patients had stage 1 (4.9%), 97 patients stage 2 (20.8%), 70 patients stage 3 (15%) and 277 patients had stage 4 disease (59.3%). Diabetes mellitus was detected in 173 (37%) patients. In this group 23 patients had stage 1 (4.9%), 97 patients stage 2 (20.8%), 70 patients stage 3 (15%) and 98 patients had stage 4 disease (56.6%). Thirty seven percent (64 patients) of the patients with diabetes were using metformin. Median time for metformin usage was 14±2,3 months. Median follow-up time was 7 months (1-88 months). Median overall survival (OS) of all pancreas cancer patients was 8 months. Surprisingly, median OS of diabetic pancreas cancer patients and non-diabetics was 9 and 8 months, respectively (statistically not significant). Median OS of diabetic patient subgroup who use metformin or not was 7 versus 10 months, respectively (statistically not significant). In the subgroup of stage 3 pancreatic cancer patients with diabetes mellitus, the median OS were 16 months and 10 months according to metformin usage or not, respectively (p=02). Conclusions: In this study, the median OS of diabetic pancreas cancer patients was superior from the non-diabetics. Multi-center prospective trials including large number of patients are needed to understand well enough the benefit of metformin in diabetic pancreas carcinoma patients.

Download Full-text