Abstract
Objectives: The present study investigated the correlation between α B-crystallin (CRYAB, HSPB5) and p53 expression in ovarian cancer and further analyzed the relationship between their expression and clinicopathology and the prognostic value of their co-expression in ovarian cancer. Methods: CRYAB and p53 expression was assessed using immunohistochemistry on ovarian cancer tumor tissues from 103 cases and validated in an independent group of 103 ovarian cancer patients. Results: High CRYAB and p53 expression rates in ovarian cancer tissues were 61.17% (63/103) and 57.28% (59/103), respectively, and their expression was positively correlated (r = 0.525, P=0.000). High CRYAB expression was significantly correlated with tumor size (P=0.028), lymph node metastasis (P=0.000), distant metastasis (P=0.005), tumor node metastasis (TNM) stage (P=0.002), and survival (P=0.000), while high p53 expression was significantly correlated with tumor size (P=0.006), pathological grade (P=0.023), lymph node metastasis (P=0.001), and survival (P=0.000). Further studies found that the high CRYAB and p53 co-expression was also significantly correlated with pathological grade (P=0.024), lymph node metastasis (P=0.000), Distant metastasis (P=0.015), TNM stage (P=0.013), and survival (P=0.000). High expression of either CRYAB or p53 and high co-expression of CRYAB and p53 were significantly correlated with poor disease-free survival (DFS) and overall survival (OS), respectively (P<0.05). Patients with high CRYAB and p53 co-expression had the worst prognoses among the groups. In addition, multivariate Cox regression models showed that high expression of either CRYAB or p53 and high co-expression of CRYAB and p53 were independent prognostic factors for DFS and OS (P<0.05). Moreover, the positive correlation and prognostic value of CRYAB and p53 expression were verified in another independent dataset. Conclusions: We demonstrated that patients with high CRYAB and p53 co-expression in ovarian cancer have significantly increased risks of recurrence, metastasis, and death compared with other patients. Therefore, more frequent follow-up of patients with high CRYAB and p53 co-expression is required. Our results also suggest that combination therapy with CRYAB inhibitors and p53 blockers may benefit future treatment of ovarian cancer patients with high co-expression of CRYAB and p53.
Highlights
Ovarian cancer is a common malignant gynecological tumor that is difficult to diagnose early, progresses rapidly, and causes high mortality
The α B-crystallin (CRYAB) protein was mainly found in the cell membrane and/or cytoplasm, and p53 was mainly expressed in the nucleus (Figure 1A)
High CRYAB expression in tumor cells was significantly correlated with tumor size (P=0.028), lymph node metastasis (P=0.000), distant metastasis (P=0.005), tumor node metastasis (TNM) stage (P=0.002), and survival (P=0.000), while high p53 expression was significantly correlated with tumor size (P=0.006), pathological grade (P=0.023), lymph node metastasis (P=0.001), and survival (P=0.000)
Summary
Ovarian cancer is a common malignant gynecological tumor that is difficult to diagnose early, progresses rapidly, and causes high mortality. 238,700 new ovarian cancer cases are diagnosed worldwide with 151,900 patient deaths [1]. The numbers of new diagnoses and deaths from ovarian cancer in China are 52,100 and 22,500, respectively [2]. 90% of ovarian cancers are epithelial malignancies. Ovarian cancer has the highest mortality rate and the worst prognosis. Chemotherapy, radiotherapy, and targeted therapy have developed rapidly in recent years, the 5-year survival for patients with ovarian cancer is only 20% [4,5]. New ovarian cancer markers are urgently needed to detect early recurrence and poor prognosis
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