Expression of S100a2 Calcium-Binding Protein Predicts Response to Pancreatectomy for Pancreatic Cancer

Biankin, Andrew V.; Kench, James G.; Colvin, Emily K.; Segara, Davendra; Scarlett, Christopher J.; Nguyen, Nam Q.; Chang, David K.; Morey, Adrienne; Lee, C.-S.; Pinese, Mark; Kuo, Samuel; Susanto, Johana M.; Cosman, Peter H.; Lindeman, GJ; Visvader, JE; Merrett, Neil D.; Musgrove, Elizabeth A.; Henshall, Susan M.; Sutherland, R. L.

doi:10.1097/01.mpa.0000335385.14896.99

Cited by 20 publications

(33 citation statements)

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“…Detailed clinicopathologic and outcome data were collected for 260 consecutive patients who had a histopathologic diagnosis of pancreatic ductal adenocarcinoma and recorded CA19.9 levels from hospitals associated with the New South Wales Pancreatic Cancer Network, Australia (NSWPCN; www.pancreaticcancer.net.au), as previously described [10, 11]. This cohort of patients was retrospectively and then prospectively recruited when the database was established in 1999.…”

Section: Methodsmentioning

confidence: 99%

The prognostic and predictive value of serum CA19.9 in pancreatic cancer

et al. 2012

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BackgroundCurrent staging methods for pancreatic cancer (PC) are inadequate, and biomarkers to aid clinical decision making are lacking. Despite the availability of the serum marker carbohydrate antigen 19.9 (CA19.9) for over two decades, its precise role in the management of PC is yet to be defined, and as a consequence, it is not widely used.MethodsWe assessed the relationship between perioperative serum CA19.9 levels, survival and adjuvant chemotherapeutic responsiveness in a cohort of 260 patients who underwent operative resection for PC.ResultsBy specifically assessing the subgroup of patients with detectable CA19.9, we identified potential utility at key clinical decision points. Low postoperative CA19.9 at 3 months (median survival 25.6 vs 14.8 months, P = 0.0052) and before adjuvant chemotherapy were independent prognostic factors. Patients with postoperative CA 19.9 levels >90 U/ml did not benefit from adjuvant chemotherapy (P = 0.7194) compared with those with a CA19.9 of ≤90 U/ml (median 26.0 vs 16.7 months, P = 0.0108). Normalization of CA19.9 within 6 months of resection was also an independent favorable prognostic factor (median 29.9 vs 14.8 months, P = 0.0004) and normal perioperative CA19.9 levels identified a good prognostic group, which was associated with a 5-year survival of 42%.ConclusionsPerioperative serum CA19.9 measurements are informative in patients with detectable CA19.9 (defined by serum levels of >5 U/ml) and have potential clinical utility in predicting outcome and response to adjuvant chemotherapy. Future clinical trials should prioritize incorporation of CA19.9 measurement at key decision points to prospectively validate these findings and facilitate implementation.

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Section: Methodsmentioning

confidence: 99%

The prognostic and predictive value of serum CA19.9 in pancreatic cancer

et al. 2012

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“…Survival after PDA resection has been associated with many factors including stage (tumor size and nodal involvement) and grade (degree of differentiation) 13 , but no one factor has been consistently prognostic 14,15 . We found that stratification by PDA transcriptional subtype provided useful prognostic information in one PDA dataset (UCSF) for which clinical annotation was available.…”

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confidence: 99%

Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy

Collisson

Sadanandam

Olson

et al. 2011

Nat Med

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1,790

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“…Importantly, moderate/high expression of S100A2 gene in pancreatic cancer contributes to gemcitabine resistance and inhibition of apoptosis due to BNIP3 repression activity 44. In addition, in a second study on patients with pancreatic cancer, S100A2 over‐expression was also associated with a poor prognosis,39 which remained prognostic following interrogation in a validation cohort 45. On the other hand, the ability of S100A proteins to predict response to chemotherapy was also observed in patients with stage IB‐IIA cervical cancer, with S100A8 and S100A9 immunohistochemical expression correlating with tumor response 38.…”

Section: Discussionmentioning

confidence: 95%

Gene‐expression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5′fluoruracil‐based adjuvant chemotherapy

Giraldez

Lozano

Cuatrecasas

et al. 2012

Intl Journal of Cancer

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Although receiving adjuvant chemotherapy after radical surgery, a disappointing proportion of patients with colorectal cancer will develop tumor recurrence. Probability of relapse is currently predicted from pathological staging, there being a need for additional markers to further select high-risk patients. This study was aimed to identify a gene-expression signature to predict tumor recurrence in patients with Stages II and III colon cancer treated with 5 0 fluoruracil (5FU)-based adjuvant chemotherapy. Two-hundred and twenty-eight patients diagnosed with Stages II-III colon cancer and treated with surgical resection and 5FU-based adjuvant chemotherapy were included. RNA was extracted from formalin-fixed, paraffin-embedded tissue samples and expression of 27 selected candidate genes was analyzed by RT-qPCR. A tumor recurrence predicting model, including clinico-pathological variables and gene-expression profiling, was developed by Cox regression analysis and validated by bootstrapping. The regression analysis identified tumor stage and S100A2 and S100A10 gene expression as independently associated with tumor recurrence. The risk score derived from this model was able to discriminate two groups with a highly significant different probability of tumor recurrence (HR, 2.75; 95%CI, 1.71-4.39; p 5 0.0001), which it was maintained when patients were stratified according to tumor stage. The algorithm was also able to distinguish two groups with different overall survival (HR, 2.68; 95%CI, 1.12-6.42; p 5 0.03). Identification of a new gene-expression signature associated with a high probability of tumor recurrence in patients with Stages II and III colon cancer receiving adjuvant 5FU-based chemotherapy, and its combination in a robust, easy-to-use and reliable algorithm may contribute to tailor treatment and surveillance strategies.

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Expression of S100a2 Calcium-Binding Protein Predicts Response to Pancreatectomy for Pancreatic Cancer

Cited by 20 publications

References 0 publications

The prognostic and predictive value of serum CA19.9 in pancreatic cancer

The prognostic and predictive value of serum CA19.9 in pancreatic cancer

Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy

Gene‐expression signature of tumor recurrence in patients with stage II and III colon cancer treated with 5′fluoruracil‐based adjuvant chemotherapy

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