Predictors of Long-Term Survival in Pancreatic Ductal Adenocarcinoma after Pancreatectomy: TP53 and SMAD4 Mutation Scoring in Combination with CA19-9

Masato Ono, Yusuke Ono, Toru Nakamura, Takahiro Tsuchikawa, Tomotaka Kuraya, Shota Kuwabara, Yoshitsugu Nakanishi, Toshimichi Asano, Aya Matsui, Kimitaka Tanaka, Yuma Ebihara, Yo Kurashima, Takehiro Noji, Soichi Murakami, Toshiaki Shichinohe, Tomoko Mitsuhashi, Yuko Omori, Toru Furukawa, Kenzui Taniue, Mayumi SuzukiAyumu Sugitani, Hidenori Karasaki, Yusuke Mizukami, Satoshi Hirano

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Background: Pancreatic ductal adenocarcinoma (PDA) is a fatal cancer for which even unfavorable clinicopathological factors occasionally fail to preclude long-term survival. We sought to establish a scoring system that utilizes measurable pre-intervention factors for predicting survival following surgical resection. Methods: We retrospectively analyzed 34 patients who died from short-term recurrences and 32 long-term survivors among 310 consecutively resected patients with PDA. A logistic regression model was used to define factors related to clinical parameters, molecular profiles of 18 pancreatic cancer-associated genes, and aberrant expression of major tumor suppressors. Results: Carbohydrate antigen 19-9 (CA19-9) had the best ability to classify patients with short-term recurrence and long-term survivors [odds ratio 21.04, 95% confidence interval (CI) 4.612–96.019], followed by SMAD4 and TP53 mutation scoring (odds ratio 41.322, 95% CI 3.156–541.035). Missense TP53 mutations were strongly associated with the nuclear expression of p53, whereas truncating mutations were associated with the absence of nuclear p53. The former subset was associated with a worse prognosis. The combination of aberrant SMAD4 and mutation types of TP53 exhibited a better resolution for distinguishing patients with short-term recurrences from long-term survivors (compared with the assessment of the number of mutated KRAS, CDKN2A, TP53, and SMAD4 genes). Calibration of mutation scores combined with CA19-9 in a logistic regression model setting demonstrated a practical effect in classifying long survivors and patients with early recurrence (c-statistic = 0.876). Conclusions: Genetic information, i.e., TP53 mutation types and SMAD4 abnormalities, combined with CA19-9, will be a valuable tool for improving surgical strategies for pancreatic cancer.

Original languageEnglish
Pages (from-to)5007-5019
Number of pages13
JournalAnnals of Surgical Oncology
Issue number8
Publication statusPublished - 2022 Aug
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Oncology


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