CLPTM1L expression predicts recurrence of patients with intermediate­ and high­risk stage IB­IIB cervical cancer undergoing radical hysterectomy followed by TP as adjuvant chemotherapy.

According to the National Comprehensive Cancer Network clinical practice guidelines of cervical cancer, concurrent chemoradiotherapy or radiotherapy is suggested for patients who receive radical hysterectomy and have intermediate- and high-risk cervical cancer. However, adjuvant chemotherapy has been increasingly chosen given the adverse events associated with chemoradiotherapy or radiotherapy and the increase in evidence regarding the efficacy of adjuvant chemotherapy. Given that adjuvant chemotherapy is not a standard treatment at present, if recurrence after adjuvant chemotherapy could be predicted, it would assist the decision of gynecological oncologists selecting which adjuvant therapy (chemotherapy or radiation therapy) to use. Cleft lip and palate transmembrane protein 1-like protein (CLPTM1L; also known as cisplatin resistance-related protein 9) is associated with apoptotic mechanisms and is related to the proliferation of the tumor cells and resistance against chemotherapy. In the present study, the association between CLPTM1L expression and recurrence of intermediate- and high-risk stage IB-IIB cervical cancer in patients undergoing radical hysterectomy followed by treatment with cisplatin and paclitaxel (TP) as adjuvant chemotherapy was determined. Patients were divided into two groups: Recurrence group and no-recurrence group. CLPTM1L expression was examined using immunohistochemistry in paraffin-embedded sections using weighted scores. Regarding the characteristics of the patients, a histology of non-squamous cell carcinoma, lymph node metastasis and parametrium invasion were more common in the recurrence group compared with the non-recurrence group. In the recurrence group, CLPTM1L expression was significantly higher than that in the no-recurrence group. Next, patients were divided into low and high-expression groups based on the weighted score with a cut-off value of 6. In the high expression group, patients exhibited a higher rate of recurrence (37.5 vs. 5.1%) and had worse overall survival. Multivariate analysis revealed that high CLPTM1L expression was independently related to recurrence. In in vitro analysis, small interfering RNA-mediated knockdown of CLPTM1L enhanced the sensitivity of cervical cancer cells to cisplatin. In conclusion, the present study revealed that CLPTM1L expression may be a predictive biomarker of recurrence of intermediate- and high-risk stage IB-IIB cervical cancer in patients undergoing radical hysterectomy followed by TP as adjuvant chemotherapy.

Fyn expression is associated with the response of patients with locally advanced uterine cervical squamous cell carcinoma to neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NAC) followed by surgery is the current standard of treatment for locally advanced uterine cervical cancer; however, its value and outcomes remain contested. Identifying biomarkers that allow for the prediction of the effect of NAC efficacy before initiation of treatment is essential, in order to assist in choosing the optimum therapeutic regimen to maximize the beneficial outcomes of treatment. In the present retrospective study, 44 patients with locally advanced uterine cervical squamous cell carcinoma who underwent NAC were divided into two groups: A NAC successful group and a NAC failure group, depending on the efficacy of NAC. Subsequently, the association between Fyn expression, a non-receptor tyrosine kinase that is a member of the Src family kinases, and NAC efficacy was determined; Fyn expression was detected by immunohistochemistry and assessed using a weighted scoring method. Additionally, the effect of Fyn knockdown on the sensitivity of a uterine cervical cancer cell line to cisplatin was determined. Notably, there were no significant differences between the two groups of patients regarding their characteristics. Regarding overall survival, the NAC successful group had a significantly longer survival time than the NAC failure group (P=0.01). Furthermore, the expression levels of Fyn in tumor tissues were significantly lower in the NAC successful group compared with those in the NAC failure group (P=0.003). The patients were subsequently divided into two groups (high expression group and low expression group) according to a cutoff value of 3, which was determined by producing a receiver operating characteristic curve from the weighted scores. The low expression group was significantly more sensitive to NAC than the high expression group (P<0.001). In vitro experiments revealed that Fyn knockdown significantly enhanced the sensitivity of uterine cancer cells to cisplatin (P<0.05). In conclusion, Fyn expression may be a potentially useful biomarker for predicting the response to NAC in patients with locally advanced uterine cervical squamous cell carcinoma, and may also be a promising molecular target for the management of uterine cancer.

T-box 2 expression is a useful indicator of the response to neoadjuvant chemotherapy for patients with locally advanced uterine cervical squamous cell carcinoma.

Platinum-based concurrent chemoradiotherapy is the standard treatment for patients with locally advanced uterine cervical squamous cell carcinoma. Reducing the tumor size by administering neoadjuvant chemotherapy (NAC) is beneficial for successful hysterectomy, resulting in a more favorable prognosis. Therefore, identifying biomarkers that predict the effectiveness of NAC in patients with cervical squamous cell carcinoma remains a priority. Cancer cells widely express T-box 2 (TBX2), which contributes to the resistance to DNA-damaging chemotherapeutic agents. The present study aimed to determine the association between TBX2 protein expression in tumor tissues and the efficacy of NAC in locally advanced uterine cervical squamous cell carcinoma using immunohistochemistry. Data from 46 patients with locally advanced uterine cervical squamous cell carcinoma were classified into two groups based on their effective or ineffective response to NAC treatment. In addition, the effect of small interfering RNA-mediated knockdown of TBX2 on the sensitivity of cervical cancer cells to cisplatin was investigated in vitro. The results revealed that there were no significant differences in patient clinicopathological features between the NAC effective and NAC ineffective groups. The overall survival of the NAC effective group was significantly improved compared with the NAC ineffective group (P=0.007). Tumors from the NAC effective group also had significantly downregulated TBX2 expression levels compared with those from the NAC ineffective group (P=0.0138). Of note, decreased TBX2 expression was indicated to be significantly associated with higher sensitivity to NAC (P=0.009). The low TBX2 expression group had a more favorable overall survival compared with the high TBX2 expression group (P=0.049). Furthermore, knockdown of TBX2 expression significantly increased cancer cell sensitivity to cisplatin in vitro. In conclusion, the results of the present study suggested that TBX2 expression may be a useful predictor of the response to NAC in patients with locally advanced uterine cervical squamous cell carcinoma.

Neutrophil-to-lymphocyte ratio is associated with sensitivity to platinum-based chemotherapy and prognosis in patients with advanced serous ovarian carcinoma.

The role of the neutrophil-to-lymphocyte ratio (NLR) in predicting sensitivity to chemotherapy and prognosis has attracted great interest in several types of cancer. In the present study, the correlation between pre-chemotherapy NLR and sensitivity to platinum-based chemotherapy and prognosis in patients with advanced serous ovarian carcinoma was examined by retrospectively reviewing the medical records of 50 patients with stage III-IV serous ovarian carcinoma from 2005 to 2012. Patients were divided into high-NLR (32 patients) and low-NLR (18 patients) groups according to a cutoff value of 2.47. This cutoff was calculated using a receiver operating characteristic (ROC) curve that demonstrated 84% specificity and 60% sensitivity. Patient characteristics, sensitivity to platinum-based chemotherapy and prognosis were subsequently compared. The results revealed no significant difference in patient characteristics between the two groups. In the low-NLR group, 14 of 18 patients (77.8%) were sensitive to platinum-based chemotherapy, whereas 11 of 32 were sensitive in the high-NLR group (34.4%) (P=0.007). Overall and disease-free survival (DFS) were significantly longer in the low-NLR than in the high-NLR group (P=0.013 and P=0.043, respectively). The current results suggested that pre-chemotherapeutical NLR may serve as a biomarker of sensitivity to platinum-based chemotherapy and prognosis in patients with advanced serous ovarian carcinoma.

PRMT1 expression predicts response to neoadjuvant chemotherapy for locally advanced uterine cervical cancer.

The standard care for patients with locally advanced cervical cancer is concurrent chemoradiotherapy. Successful neoadjuvant chemotherapy (NAC) can reduce tumor size and enable patients to be eligible for a hysterectomy, which can improve their prognosis. Selecting the right candidate for NAC is important since NAC failure results in switching to radiation therapy and can lead to a worse prognosis due to a delay in the initiation of the core therapy. Therefore, the identification of biomarkers that can predict the effect of NAC is essential. Previous reports have suggested a relationship between protein arginine methyltransferase (PRMT1) and chemoresistance in several types of cancer. PRMT1 has been demonstrated to methylate apoptosis signal-regulated kinase 1 and to inhibit its activity, thereby contributing to chemoresistance. The present study investigated the association between PRMT1 expression and the efficacy of NAC in locally advanced cervical cancer. Data from 53 patients with locally advanced uterine cervical cancer who were classified into two groups based on effective (n=28) and ineffective (n=25) responses to NAC treatment were evaluated. PRMT1 expression was investigated by immunohistochemistry and scored using a weighted scoring system. Additionally, the present study investigated the effect of RNA interference-mediated downregulation of PRMT1 on the sensitivity of cervical cancer cells to cisplatin in vitro. The results demonstrated that the NAC effective group had significantly lower weighted PRMT1 scores than the NAC ineffective group (P=0.030). In addition, lower tumor expression levels of PRMT1 were significantly associated with increased sensitivity to NAC (P=0.033). Furthermore, downregulation of PRMT1 expression in cervical cancer cells markedly improved their sensitivity to cisplatin in vitro. The present study suggested that PRMT1 expression has potential as a predictive marker of the efficacy of NAC in patients with locally advanced cervical cancer. This finding can contribute to improvements in the prognosis of these patients.

PRMT1 expression predicts sensitivity to platinum-based chemotherapy in patients with ovarian serous carcinoma.

Patients with ovarian serous carcinoma are generally diagnosed at an advanced disease stage. The standard treatment for these patients is maximal debulking surgery followed by platinum-taxane combination chemotherapy. Despite initially responding well, more than half of patients become refractory to first-line chemotherapy. Upregulation of protein arginine methyltransferase 1 (PRMT1) expression has been demonstrated to methylate apoptosis signal-regulated kinase 1 and inhibit its activity, thereby contributing to chemoresistance. The present study investigated the association between PRMT1 expression and sensitivity to platinum-based chemotherapy in 51 patients with ovarian serous carcinoma (International Federation of Gynecology and Obstetrics stages III and IV), and the effect of RNA interference-mediated downregulation of PRMT1 on the sensitivity of ovarian cancer cells to cisplatin and carboplatin in vitro. Immunohistochemistry of tumor specimens was used to compare the expression levels of PRMT1, a Cell Counting Kit-8 assay and small interfering RNA transfection were performed for chemosensitivity assays, and reverse transcription-quantitative PCR was used to examine PRMT1 mRNA expression. Patients were divided into platinum-sensitive (n=26) and platinum-resistant (n=25) groups. PRMT1 expression was significantly lower in the platinum-sensitive group than in the platinum-resistant group (P=0.019). When patients were categorized according to PRMT1 expression, those in the low PRMT1 expression group were more sensitive to platinum-based chemotherapy than those in the high PRMT1 expression group (P=0.01). Additionally, in vitro experiments revealed that suppression of PRMT1 expression by siRNA significantly increased the sensitivity of human ovarian serous carcinoma cells to cisplatin and carboplatin (P<0.05). In conclusion, PRMT1 expression could predict sensitivity to platinum-based chemotherapy in patients with ovarian serous carcinoma.