Postoperative serum CEA and CA125 levels are supplementary to perioperative CA19-9 levels in predicting operative outcomes of pancreatic ductal adenocarcinoma.

BACKGROUND: Carbohydrate antigen (CA19-9) is a well-established marker to monitor disease status after resection of pancreatic cancer. However, few serum markers have been reported to improve the prognostic ability of postoperative CA19-9, especially in patients with normal postoperative CA19-9. METHODS: A total of 353 patients with pancreatic ductal adenocarcinoma treated by radical resection were reviewed retrospectively, and a prospective cohort including 142 patients with resectable pancreatic head carcinoma was analyzed as a validation cohort. Perioperative CA19-9 and postoperative serum markers (CEA, CA242, CA72-4, CA50, CA125, CA153, and AFP) were investigated. RESULTS: Patients with postoperative normalization of CA19-9 had improved survival times (recurrence-free survival: 11.9 months; overall survival: 22.5 months) compared with those with decreased but still elevated postoperative CA19-9 (recurrence-free survival: 6.8 months, P < .001; overall survival: 13.5 months, P < .001) or those with increased postoperative CA19-9 (recurrence-free survival: 3.5 months, P < .001; overall survival: 7.9 months, P < .001), which was similar to those with consistently normal CA19-9 during perioperative periods (recurrence-free survival: 10.6 months, P = .799; overall survival: 24.1 months, P = .756). Normal postoperative CA19-9 levels were an independent indicator for a positive outcome after operation, regardless of preoperative CA19-9 levels. Elevated postoperative CEA and CA125 were identified further as independent risk factors for patients with normal postoperative CA19-9, while elevated postoperative CA125 and nondecreased postoperative CA19-9 were independent prognostic markers for patients with elevated postoperative CA19-9. CONCLUSION: The postoperative monitoring of CEA and CA125 provided prognostic significance to the measurement of CA19-9 in pancreatic cancer after resection.

Mutant p53 determines pancreatic cancer poor prognosis to pancreatectomy through upregulation of cavin-1 in patients with preoperative serum CA19-9 ≥ 1,000 U/mL.

Patients with pancreatic ductal adenocarcinoma (PDAC) and preoperative CA19-9 ≥ 1,000 U/mL that does not decrease postresection have the worst prognosis, but the mechanism is unclear. Here, we elucidated the relationship between this signature and driver-gene mutations, and the cavins/caveolin-1 axis. Four major driver-genes (KRAS, TP53, CDKN2A/p16, and SMAD4/DPC4) that are associated with PDAC and five critical molecules (cavin-1/-2/-3/-4 and caveolin-1) in the cavins/caveolin-1 axis were screened by immunohistochemistry in tumor tissue microarrays. Additionally, six pancreatic cancer cell lines and a spleen subcapsular inoculation nude mouse model were also used. Overexpression of mutant p53 was the major mutational event in patients with the CA19-9 signature. Cavin-1 was also overexpressed, and mutant p53 correlated directly with high cavin-1 expression in pancreatic cancer cell lines and tumor specimens (P < 0.01). Furthermore, mutant p53(R172H) upregulated cavin-1 and promoted invasiveness and metastasis of pancreatic cancer cells in vitro and in vivo. Finally, combination of mutant p53 and high cavin-1 density indicated the shortest survival for patients with PDAC after resection (P < 0.001). Mutant p53-driven upregulation of cavin-1 represents the major mechanism of poor outcome for PDAC patients with the CA19-9 signature after resection, indicating that inhibition of cavin-1 may improve the long-term efficacy of pancreatectomy.

Serum CA125 is a novel predictive marker for pancreatic cancer metastasis and correlates with the metastasis-associated burden.

This study evaluated potential of serum tumor markers to predict the incidence and intensity of pancreatic cancer metastasis as well as patient survival. Retrospective records from 905 patients and prospective data from 142 patients were collected from two high-volume institutions. The levels of eight serum tumor markers (CA19-9, CEA, CA242, CA72-4, CA50, CA125, CA153, and AFP) commonly used in gastroenterological cancer were analyzed in all stages of pancreatic cancer. Serum CA125 levels were the most strongly associated with pancreatic cancer metastasis and were higher in patients with metastatic disease than those without. CA125 levels increased with increasing metastasis to lymph nodes and distant organs, especially the liver. High baseline CA125 levels predicted early distant metastasis after pancreatectomy and were associated with the presence of occult metastasis before surgery. An optimal CA125 cut-off value of 18.4 U/mL was identified; patients with baseline CA125 levels of 18.4 U/mL or higher had poor surgical outcomes. In addition, high serum CA125 levels coincided with the expression of a metastasis-associated gene signature and with alterations in "driver" gene expression involved in pancreatic cancer metastasis. CA125 may therefore be a promising, noninvasive, metastasis-associated biomarker for monitoring pancreatic cancer prognosis.