RPA3 is a potential marker of prognosis and radioresistance for nasopharyngeal carcinoma

Abstract

Radioresistance‐induced residual and recurrent tumours are the main cause of treatment failure in nasopharyngeal carcinoma (NPC). Thus, the mechanisms of NPC radioresistance and predictive markers of NPC prognosis and radioresistance need to be investigated and identified. In this study, we identified RPA3 as a candidate radioresistance marker using RNA‐seq of NPC samples. In vitro studies further confirmed that RPA3 affected the radiosensitivity of NPC cells. Specifically, the overexpression of RPA3 enhanced radioresistance and the capacity for DNA repair of NPC cells, whereas inhibiting RPA3 expression sensitized NPC cells to irradiation and decreased the DNA repair capacity. Furthermore, the overexpression of RPA3 enhanced RAD51 foci formation in NPC cells after irradiation. Immunohistochemical assays in 104 NPC specimens and 21 normal epithelium specimens indicated that RPA3 was significantly up‐regulated in NPC tissues, and a log‐rank test suggested that in patients with NPC, high RPA3 expression was associated with shorter overall survival (OS) and a higher recurrence rate compared with low expression (5‐year OS rates: 67.2% versus 86.2%; 5‐year recurrence rates: 14.8% versus 2.3%). Moreover, TCGA data also indicated that high RPA3 expression correlated with poor OS and a high recurrence rate in patients with head and neck squamous cell carcinoma (HNSC) after radiotherapy. Taken together, the results of our study demonstrated that RPA3 regulated the radiosensitivity and DNA repair capacity of NPC cells. Thus, RPA3 may serve as a new predictive biomarker for NPC prognosis and radioresistance to help guide the diagnosis and individualized treatment of patients with NPC.

Germline Polymorphisms and Length of Survival of Nasopharyngeal Carcinoma: An Exome‐Wide Association Study in Multiple Cohorts

“…In addition, previous studies have demonstrated the expression of RPA1 and RPA2 are potential prognostic factors in multiple cancers, [ 17c,19 ] and likewise, RPA3 has been associated with survival of patients with gastric cancer, [ 20 ] hepatocellular cancer, [ 21 ] and NPC. [ 22 ] These findings suggest that RPA1 and other subunits of RPA complex might be important modulators for the progression of several human cancers.…”

MicroRNA‐372 enhances radiosensitivity while inhibiting cell invasion and metastasis in nasopharyngeal carcinoma through activating the PBK‐dependent p53 signaling pathway

“…Nasopharyngeal carcinoma (NPC), a highly metastasizing and invasive cancer, is widespread in southern China and southeast Asia with environmental influence, Epstein‐Barr virus infection, and genetic factors serving as the main inducements . Besides, NPC is often found in epithelial cells with a particular endemic distribution, and its mortality is greatly reduced by effective systemic agents, population screening as well as radiotherapy . Although NPC patients diagnosed at early stages may be effectively cured by radiotherapy, NPC patients at advanced stage still face unsatisfactory treatment efficacy owing to frequently occurred metastasis and local recrudesce .…”

Distinct expression and prognostic values of the replication protein A family in gastric cancer

“…The members of the RPA family are essential components of multiple pathways that influence DNA replication, recombination, repair and damage signaling (4)(5)(6)(7)(8)23,24). Clinical studies have determined that RPAs are upregulated in various cancer types, including hepatocellular and esophageal carcinoma, and colon and bladder cancer (5,(7)(8)(25)(26)(27), and that this frequently correlates with poor prognosis (28)(29)(30). Nonetheless, the influence of RPAs on GC progression is yet to be elucidated.…”