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UCP2 expression may represent a predictive marker of neoadjuvant chemotherapy effectiveness for locally advanced uterine cervical cancer.

ABSTRACT: Concurrent chemoradiotherapy is the standard treatment for locally advanced uterine cervical cancer. However, effective neoadjuvant chemotherapy (NAC) can reduce tumor size and facilitate hysterectomy for locally advanced uterine cervical cancer. NAC treatment could improve the prognosis of patients with locally advanced cervical cancer. However, if NAC is ineffective, radiotherapy must be pursued. This causes a delay in initiating the core treatment and results in a worse prognosis. Therefore, the identification of predictive markers of whether NAC is likely to be effective for the treatment of locally advanced uterine cervical cancer could improve patient prognosis. Uncoupling protein 2 (UCP2) is broadly expressed in cancer cells, and suppresses mitochondrial reactive oxygen species (ROS) production. UCP2 contributes to both carcinogenesis and chemoresistance by reducing ROS. Downregulation of UCP2 results in significantly increased cell death following chemotherapy. The present study investigated the association between UCP2 expression and NAC effectiveness. A total of 58 patients with locally advanced uterine cervical cancer (stage IIIA or IIIB) treated at Osaka City University Hospital between April 1995 and March 2010 were examined. Tumor tissue samples were obtained by punch biopsy prior to NAC. UCP2 expression was examined immunohistochemically and scored using a weighted scoring system. Patients were divided into NAC effective (n=34) and ineffective (n=24) groups. Furthermore, UCP2 expression in human uterine cervical cancer cells was inhibited by genipin, and changes in cisplatin sensitivity were examined. UCP2 weighted score was higher in the NAC ineffective group than in the NAC effective group (P=0.038). Additionally, the low UCP2 expression group was more sensitive to NAC than the high UCP2 expression group (P=0.041). Sensitivity to cisplatin was significantly increased when UCP2 was inhibited in human uterine cervical cancer cells in vitro. UCP2 expression may become a predictive marker of whether NAC is effective for patients with locally advanced uterine cervical cancer, which could improve patient prognosis.

SUBMITTER: Imai K

PROVIDER: S-EPMC5494603 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Project description:BackgroundThe efficacy of neoadjuvant chemotherapy is closely related to the long-term prognosis of colorectal cancer (CRC) patients. Apparent diffusion coefficient (ADC) is an index in dynamic enhanced magnetic resonance imaging (MRI), reflecting the density of tumor cells. ADC has been shown to be related to the efficacy of neoadjuvant chemotherapy in other malignant tumors, but there is still a lack of relevant research in CRC patients.MethodsA total of 128 patients with CRC treated with neoadjuvant chemotherapy in The First Affiliated Hospital of Xiamen University from January 2016 to January 2017 were retrospectively collected. According to the response after neoadjuvant chemotherapy, the patients were divided into an objective response group (n=80) and a control group (n=48). The clinical characteristics and ADC levels of the two groups were compared, and the predictive value of ADC on the efficacy of neoadjuvant chemotherapy was analyzed. The patients were followed up for 5 years to observe the difference of survival rate between the two groups, and further analyzed the correlation between ADC and survival rate.ResultsCompared with the control group, the tumor size in the objective response group was significantly reduced (3.32±1.60 vs. 5.07±2.19 cm, P=0.000); ADC significantly increased (1.23±0.18 vs. 0.98±0.18 ×10-3 mm2/s, P=0.000); albumin significantly increased (39.32±4.14 vs. 37.46±4.18 g/L, P=0.016); the proportion of patients with poorly differentiated or undifferentiated tumor cells was significantly lower (51.25% vs. 72.92%, P=0.016); and the 5-year mortality decreased significantly (40.00% vs. 58.33%, P=0.044). ADC had the highest predictive value of objective response for locally advanced CRC patients after neoadjuvant chemotherapy, and the area under the curve (AUC) was 0.834 [95% confidence interval (CI): 0.765-0.903, P=0.000]; ADC had certain predictive value for the 5-year survival of locally advanced CRC patients, and the AUC was 0.778 (95% CI: 0.696-0.861, P=0.000). ADC >1.055×10-3 mm2/s, tumor size <4.1 cm, and moderately or well differentiated tumors were favorable factors for patients with locally advanced CRC to obtain objective response after neoadjuvant chemotherapy (P<0.05).ConclusionsADC could be used as a predictor of the efficacy of neoadjuvant chemotherapy in locally advanced CRC patients.

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UCP2 expression may represent a predictive marker of neoadjuvant chemotherapy effectiveness for locally advanced uterine cervical cancer.

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