Correlation Between RAB27B and p53 Expression and Overall Survival in Pancreatic Cancer

Abstract

ObjectivesRAB27B is a member of the Rab family GTPases involved in vesicle trafficking, and p53 has recently been implicated in regulating the exosome secretion pathway. Because exosome secretion plays an important role in modulating tumor microenvironment and invasive growth, we hypothesized that RAB27B and p53 expression might be associated with the aggressive behavior in pancreatic ductal adenocarcinoma, one of the most deadly human malignancies.MethodsWe determined protein expression of RAB27B and p53 in 260 pancreatic tissues (186 malignant and 74 normal or benign) by immunohistochemistry analysis on tissue microarray and their correlation with patients' clinical parameters and overall survival.ResultsWe found that a high RAB27B protein expression (RAB27B+) was significantly associated with perineural and vascular invasion, as well as distant metastasis. Patients with a high RAB27B expression had significantly poorer overall survival in both univariate and multivariate analyses. A significant correlation between RAB27B and p53 expression was observed.ConclusionsOur data indicate that RAB27B expression is an independent prognostic marker for pancreatic ductal adenocarcinoma and suggest that RAB27B-regulated exosome secretion pathway represents a novel therapeutic target in pancreatic cancer.

Exosomes: Navigating a New Route in Pancreatic Cancer

“…Moreover, RAB27A expression was shown to be an independent prognostic marker for PDAC, indicating that the RAB27A-regulated exosome secretion pathway may represent a novel therapeutic target in pancreatic cancer. Consistent with these data, another study showed that RAB27B and p53 expression are negatively correlated with the overall survival of pancreatic cancer patients [79,80]. Together, as per Table 1, these surprising results predict a promising future for improved early diagnosis of patients with pancreatic cancer, and motivate continued exploration into using exosomes as a source of novel biomarkers.…”

YKT6 expression, exosome release, and survival in non-small cell lung cancer

“…Although these preliminary results require further validation with a greater number of plasma samples, they provide the first indications that YKT6 levels in the tumor may act as a surrogate of exosome levels in plasma. Of note, other genes related to exosome release have also been previously related to cancer; for example, high Rab27B levels have been linked to poor prognosis in bladder [29], pancreatic [30] and colorectal cancer [31] and hepatocellular carcinoma [26]. …”

Effect of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in pancreatic cancer

“…Increasing evidence demonstrates that the overexpression of CCNB1 is observed in certain number of human cancers including colorectal cancer, breast cancer, and PC (Fang et al, ; Nimeus‐Malmstrom et al, ; Zhou et al, ). Located on chromosome 17p, p53 regulates DNA repair, cell cycle, apoptosis, and senescence and therefore plays an important role in genomic stability maintenance and tumor prevention (J. Liu, Zhang, Hu, & Feng, ; Zhao et al, ). The p53 tumor suppressor gene mutates in more than 50% of human malignancies (Zhao et al, ) and is mutated in 50–75% of PC cells (Morton et al, ).…”

“…Located on chromosome 17p, p53 regulates DNA repair, cell cycle, apoptosis, and senescence and therefore plays an important role in genomic stability maintenance and tumor prevention (J. Liu, Zhang, Hu, & Feng, ; Zhao et al, ). The p53 tumor suppressor gene mutates in more than 50% of human malignancies (Zhao et al, ) and is mutated in 50–75% of PC cells (Morton et al, ). Moreover, the p53 tumor suppressor pathway is also pivotal in mediating the response of commonly used cancer therapies (Grochola, Zeron‐Medina, Meriaux, & Bond, ).…”