High expression of XPA confers poor prognosis for nasopharyngeal carcinoma patients treated with platinum-based chemoradiotherapy

Abstract

In this study, we tried to explore if xeroderma pigmentosum complementation group-A (XPA) expression is likely a prognostic prediction factor for locally advanced nasopharyngeal carcinoma (NPC) patients treated with platinum-based chemoradiotherapy, which was considered to bring chemotherapy-related severe toxicity compared with radiotherapy alone. Firstly, MTT assay revealed that downregulating XPA expression in NPC HONE1 and CNE1 cells decreased IC50 of cisplatin and sensitized cells to cisplatin. XPA expression was detected by immunohistochemistry in cancer tissues from locally advanced NPC patients treated with platinum-based chemoradiotherapy. The relationships between XPA expression and clinicopathologic features, overall survival and progression-free survival of patients were evaluated. The results showed that XPA expression was not associated with clinicopathologic parameters, but was likely an independent prognostic factor for patient survival. High XPA level predicts a poor prognosis, and the prediction values were higher in subgroups of younger, higher EBV antibody titer, or treated with concurrent chemoradiotherapy. Combining XPA levels and T/N classifications, we successfully classified these patients into low, medium and high risk groups for platinum-based chemoradiotherapy. These findings suggest that XPA levels may be a potential predictor of prognosis in locally advanced NPC patients treated with platinum-based chemoradiotherapy, and helpful for selecting patients likely to need and benefit from this treatment in future.

XPA expression is a predictive marker of the effectiveness of neoadjuvant chemotherapy for locally advanced uterine cervical cancer

“…Therefore, it is likely that upregulation of XPA expression would increase platinum resistance. Indeed, XPA expression has been reported to correlate with the resistance of nasopharyngeal carcinoma and lung cancer cell lines to platinum-based therapy (17,18,25).…”

“…The xeroderma pigmentosum complementation group A (XPA) protein is an indispensable factor for NER. Several reports have shown that XPA recognizes and verifies DNA damage sites, stabilizes repair intermediates, and contributes to the induction of other NER-associated factors (19)(20)(21)(22)(23)(24) (17)(18)(19)(20)(21)(22)(23)(24)(25). However, the role of XPA in the response of uterine cervical cancer cell lines and uterine cervical cancer patients to cisplatin is not clear.…”

The loss-of-function mutations and down-regulated expression of ASB3 gene promote the growth and metastasis of colorectal cancer cells

“…Real-time quantitative PCR (qPCR) analysis was conducted as described previously [23]. Briefly, total RNA was extracted with Trizol Reagent (Invitrogen), reversely transcribed into cDNA with M-MLV reverse transcriptase (Promega, Madison, WI, USA), and sequentially subjected to qPCR analysis with the SYBR Green PCR Kit (Invitrogen) using primers shown in Table 2.…”

“…1a) and the percentage of corresponding positive area (P 1 -P 3 ) were evaluated by two pathologists who were blinded to clinical parameters. The ASB3 protein levels were presented as H score: H score = I 1  × P 1  + I 2 × P 2  + I 3  × P 3 [23, 28, 29]. …”

Overview of Xerodermatic Pigmentsum Mutations, Prognosis, and Treatment

“…In the past, prognosis was a reduced life expectancy as a result of skin cancers or neurological complications [7]. However according to recent research, normal lifespan is possible for patients without neurological problems who are cautious about exposure to UV and protecting the skin.…”