The Expression of ZNF268 and Its Role in The Cisplatin-based Chemoresistance of Breast Cancer.

Objective: Breast cancer is one of the most prevalent cancers in females worldwide and is one of the leading causes of cancer death and disability in women. Multiple therapies have been applied to breast cancer treatment; however, the long-term survival rate remains low. Although cisplatin has been widely utilized for cancer therapy, chemoresistance still influences the outcome. Methods: After collecting the breast cancer cell line MDA-MB-231 treated with or without cisplatin and sample information from The Cancer Genome Atlas Program (TCGA), we screened out their common parameters and influences on the prognoses of patients' potential targets. Surgical excisional tissue sections of patients with breast cancer who were admitted and treated in the Department of Breast and Thyroid Surgery, Liuzhou People's Hospital from 2017 to 2020 was collected and follow up. After a series of assays combined with clinical information, we tested the reliability of the target. Results: We found that a high expression level of ZNF268 in breast cancer cell lines significantly enhances the sensitivity to cisplatin, contrary to the effects of low expression. Furthermore, a significantly worse prognosis was observed in patients with a high expression of ZNF268 after cisplatin chemotherapy. Conclusion: The expression level of ZNF268 in breast cancer patients after cisplatin chemotherapy may become a potential target to predict the chemoresistance of patients to cisplatin. This study provides a novel idea for improving breast cancer treatment and survival rates.

A Novel Pyroptosis-Associated Long Non-coding RNA Signature Predicts Prognosis and Tumor Immune Microenvironment of Patients With Breast Cancer.

Background: Pyroptosis, a kind of programmed cell death characterized by the rupture of cell membranes and the release of inflammatory substances, plays an important role in the occurrence and development of cancer. However, few studies focus on the pyroptosis-associated long non-coding RNAs (lncRNAs) in breast cancer (BC). The prognostic value of pyroptosis-associated lncRNAs and their relationship with tumor microenvironment (TME) in BC remain unclear. The purpose of this study was to explore the prognostic role of pyroptosis-associated lncRNAs and their relationship with TME in BC. Methods: The transcriptome data and clinical data of female BC patients were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 937 patients were randomly assigned to either training set or validation set. A pyroptosis-associated lncRNA signature was constructed in the training set and verified in the validation set. Functional analysis and immune microenvironment analysis related to pyroptosis-associated lncRNAs were performed. A nomogram based on the risk score and clinical characteristics was established. Results: A 9-pyroptosis-associated lncRNA signature was constructed to separate BC patients into two risk groups. High-risk patients had poorer prognosis than low-risk patients. The risk score was proven to be an independent prognostic factor by multivariate Cox regression analysis. Function analysis and immune microenvironment analysis showed that low-risk BC tended to be an immunologically "hot" tumor. A nomogram was constructed with risk score and clinical characteristics. Receiver operating characteristic curve (ROC) analysis demonstrated credible predictive power of the nomogram. The area under time-dependent ROC curve (AUC) reached 0.880 at 1 year, 0.804 at 3 years, and 0.769 at 5 years in the training set, and 0.799 at 1 year, 0.794 at 3 years, and 0.728 at 5 years in the validation set. Conclusion: We identified a novel pyroptosis-associated lncRNA signature that was an independent prognostic indicator for BC patients. Pyroptosis-associated lncRNAs had potential relationship with the immune microenvironment and might be therapeutic targets for BC patients.

CircGFRA1 facilitates the malignant progression of HER-2-positive breast cancer via acting as a sponge of miR-1228 and enhancing AIFM2 expression.

CircRNAs (circular RNA) are reported to regulate onset and progress multiple cancers. Nonetheless, the function along with the underlying mechanisms of circRNAs in HER-2-positive breast cancer (BC) remains unclear. CircRNA microarrays were performed to elucidate expression profiles of HER-2-positive BC cells. circRNA levels were quantified using qRT-PCR assay. Various in vitro along with in vivo assays were employed to further explore the effects of circGFRA1 in the progress of HER-2-positive BC and interactions of circGFRA1, miR-1228 and AIFM2 in Her-2-positive BC. CircGFRA1 was remarkably upregulated in HER-2-positive BC. Knockdown of circGFRA1 could attenuate HER-2-positive BC progression by inhibiting the proliferation, infiltration and migratory ability of HER-2-positive BC cells. Through ceRNA mechanism, circGFRA1 could bind to miR-1228 and alleviate inhibitory activity of miR-1228 on targeted gene AIFM2. In summary, circGFRA1-miR-1228-AIFM2 axis regulates HER-2-positive BC. CircGFRA1 is a novel promising treatment option for HER-2-positive BC.

Age as Indicator in the Selection of Surgery Modalities in Early Glottic Cancer.

PURPOSE: Local failure after endoscopic laryngeal surgery (ELS) for early glottic cancer mounts a challenge to researchers to investigate risk factors of recurrence. The present study was therefore designed to explore the prognostic factors in patients who underwent ELS for early glottic cancer. PATIENTS AND METHODS: We reviewed 328 patients with T1-2N0 glottic cancer who were treated with either ELS or open surgery between 2007 and 2018 at our institution. Survival, univariate and multivariate analyses were performed in different groups (ELS vs open surgery; < 65 vs ≥ 65 years). RESULTS: Age was discovered to be the independent prognostic factor of DFS for patients treated with ELS (HR = 3.673, p = 0.003), but not for patients who underwent open surgery. Survival analysis performed on young patients (< 65 years) showed that survival outcomes between different surgery modalities were significantly different (ELS vs open surgery: five-year DFS: 72.5 vs 84.7%, p = 0.034). Univariate and multivariate analyses further confirmed the finding, whereas these results did not appear in old patients (≥ 65 years). CONCLUSION: Young patients (< 65 years) treated with ELS had less favorable oncologic outcomes than those treated with open surgery. Young patients (< 65 years) are advised to consider open surgery over ELS.

Forkhead box O1 targeting replication factor C subunit 2 expression promotes glioma temozolomide resistance and survival.

BACKGROUND: Additional mechanisms of temozolomide (TMZ) resistance in gliomas remain uncertain. The aim of this study was to identify another DNA repair mechanism involving forkhead box O1 (FoxO1) and replicator C2 (RFC2) in gliomas. METHODS: We established glioma cells against TMZ, U87R, by exposure to TMZ. Proliferation rate Cell counting kit-8 (CCK8) was used, and epithelial-mesenchymal transition (EMT)-related markers were detected by western blot. The association between FoxO1 and RFC2 was analyzed by heat maps and scatter plot, and Real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to detect the effect of FoxO1 on the expression of RFC2. The regulation effect of FoxO1 on RFC2 expression was analyzed by luciferase reporter gene assay. Knockdown of FoxO1/RFC2 was achieved via short hairpin RNA (shRNA), the effect of knockdown on the proliferation was determined by CCK8 assay and colony formation assay, and apoptosis was examined by flow cytometry and immunoblotting. RESULTS: The TMZ-resistant glioma cell line, U87R, was established. The FoxO1 and RFC2 proteins increased significantly in U87R. The expression of FoxO1 and RFC2 were positively related in glioma tissues. We found that FoxO1 contributes to TMZ resistance and cell survival via regulating the expression of RFC2. Moreover, FoxO1 functions as a transcriptional activator to RFC2 by binding to the promoter of RFC2. Furthermore, knockdown of FoxO1/RFC2 suppressed cell proliferation, TMZ resistance, and induced apoptosis in U87R. CONCLUSIONS: The FoxO1/RFC2 signaling pathway promotes glioma cell proliferation and TMZ resistance, suggesting that the FoxO1/RFC2 pathway may be a potential target for TMZ-resistant glioma therapy.

High Pretreatment LDH Predicts Poor Prognosis in Hypopharyngeal Cancer.

BACKGROUND: Elevated pretreatment lactate dehydrogenase (LDH) has been associated with poor prognosis in various malignancies; however, its prognostic role in hypopharyngeal cancer remains elusive. In this study, we aimed to assess the association between pretreatment LDH and clinical outcome of hypopharyngeal cancer. METHODS: We retrospectively collected 198 hypopharyngeal cancer patients treated with surgery in our institution between 2004 and 2018. The prognostic role of pretreatment LDH was explored by using univariate and multivariate analyses. Besides, subgroup analysis was performed based on T stage. RESULTS: Three-year and Five-year of disease-free survival (DFS, 67.0 vs. 57.4%, 65.8 vs. 39.8%, p = 0.007) and overall survival (OS, 74.8 vs. 68.9%, 66.8 vs. 50.8%, p = 0.006) exhibited significant differences between low LDH level and high LDH level groups. Univariate analysis showed that pretreatment elevated serum LDH served as an unfavorable determinant with regard to DFS and OS. Further multivariate analysis also confirmed that LDH was an independent predictor for DFS and OS. Additionally, N status and age were also found to be significantly associated with both DFS and OS. CONCLUSION: Pretreatment elevated serum LDH is an inferior prognostic factor for patients with hypopharyngeal cancer. These results should be validated by more multicenter and prospective studies.

Corrigendum: AFAP1-AS1 Promotes Epithelial-Mesenchymal Transition and Tumorigenesis Through Wnt/ß-Catenin Signaling Pathway in Triple-Negative Breast Cancer.

[This corrects the article DOI: 10.3389/fphar.2018.01248.].

Postoperative adjuvant radiation improves local control in surgically treated FIGO stage I-II small cell carcinoma of the cervix.

OBJECTIVE: To determine the prognostic effect of adjuvant radiation and clinicopathological variables in surgically treated patients with small cell carcinoma of the cervix (SCCC). METHODS: Clinical data of SCCC patients with International Federation of Gynaecology and Obstetrics (FIGO) stage I-II underwent radical surgery from May 2000 to August 2014 at Sun Yat-sen Memorial Hospital were retrospectively reviewed. Forty-three patients with SCCC were included to this study. Chi-square test or Fisher's exact test, Student's t test or Mann-Whitney U test, Kaplan-Meier method and multivariate analysis of Cox proportional hazards regression were used for statistical analysis. P < 0.05 was considered to be statistically significant. RESULTS: Among 43 patients (median age, 49 years old) recruited, 25(58.1%) had stage I, 18(41.9%) had stage II disease. The 5-year overall survival (OS) rate was 39.54%, and the 5-year disease free survival (DFS) was 27.91%. Distant metastasis was the main cause of treatment failure (71.9%). Patients with adjuvant chemoradiation displayed lower rate of local recurrence than those with adjuvant chemotherapy (10.7% vs 60.0%, P < 0.0001). Multivariable analysis identified lymph node metastasis as a significant prognostic factor for both DFS and OS (P = 0.001, 0.004 respectively). Age was also an independent predictor of OS (P = 0.004). Adjuvant radiation appeared to significantly improve DFS (HR = 0.383, 95% CI, 0.185-0.791), but not OS. CONCLUSIONS: Adjuvant radiotherapy could improve the local control and prolong DFS in surgically treated SCCC. However, a large prospective clinical trial is needed to confirm this.

Definitive radiotherapy or chemoradiotherapy for distal rectal cancer with early stage of cT1-2N0.

Objectives: Patients with early-stage distal rectal cancer, if treated with radical surgery, usually suffer a poor quality of life. Definitive radiotherapy or chemoradiotherapy may be another treatment option for them. The aim of this study was to evaluate the role of definitive external beam radiotherapy or chemoradiotherapy in treating distal rectal cancer with stage cT1-2N0. Methods: We performed a retrospective study of 231 distal rectal cancer patients who were staged as cT1-2N0 from March 2002 to March 2015. All patients were treated by definitive radiotherapy or chemoradiotherapy. Overall survival (OS), progression-free survival (PFS), and short-term efficacy were analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with PFS, local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) for the whole group. Results: For the whole group, 135 patients (58.4%) achieved clinical complete response (cCR). The 5-year OS, PFS, and LRFS were 86.19%, 83.30%, and 92.50%, respectively. Patients with cCR acquired better survival than those with non-cCR. In multivariable analysis, it revealed that clinical stage, carcinoembryonic antigen (CEA level) and concurrent chemotherapy were independent predictors of PFS. Conclusion: Definitive radiotherapy or chemoradiotherapy may be feasible in some early-stage distal rectal cancer regarding its favorable efficacy.

Selective use of concurrent chemotherapy in elderly cervical cancer patients treated with definitive radiotherapy: experience from two institutions.

Background: Whether concurrent chemotherapy could bring about better oncological outcomes in elderly patients receiving definitive radiotherapy is still unknown. So, the purpose of this study was to find out whether it is essential for elderly patients to undergo concurrent chemotherapy. Methods: We performed a retrospective study of 246 elderly cervical cancer patients who were treated with definitive radiotherapy or chemo-radiation between August 2004 and August 2015. All patients were divided into two groups according to whether they were receiving concurrent chemotherapy or not. Overall survival (OS) and disease-free survival (DFS) were compared between the two groups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival, and distant metastasis-free survival (DMFS). Results: The 5-year OS in the radiotherapy and chemo-radiation groups were 72.89% and 82.25%, respectively. A significant difference was found between the two groups (P=0.016). The 5-year DFS in the radiotherapy and chemo-radiaton groups were 58.19% and 75.52%, respectively, also with a significant difference between the two groups (P=0.028). Further subgroup analysis showed that in patients with negative lymph nodes, there were no differences in both OS and DFS between patients who did and did not receive concurrent chemotherapy. However, in patients with positive lymph nodes, patients who received concurrent chemotherapy acquired better OS and DFS than those who did not. Multivariable analysis showed that concurrent chemotherapy was an independent predictor of DFS and DMFS. Conclusion: Concurrent chemotherapy could improve oncological outcomes in elderly cervical cancer patients with positive lymph nodes, but not in those with negative lymph nodes.

A Pairwise Meta-Analysis of Induction Chemotherapy in Nasopharyngeal Carcinoma.

BACKGROUND: Locoregionally advanced nasopharyngeal carcinoma has high risk of distant metastasis and mortality. Induction chemotherapy is commonly administrated in clinical practice, but the efficacy was quite controversial in and out of randomized controlled trials. We thus conducted this pairwise meta-analysis. MATERIALS AND METHODS: Trials that randomized patients to receive radiotherapy or concurrent chemoradiotherapy with or without induction chemotherapy were identified via searches of PubMed, MEDLINE, and ClinicalTrials.gov. RESULTS: A total of ten trials (2,627 patients) were included. The pooled hazard ratios (HRs) based on fixed effect model were 0.68 (95% confidence interval [CI] 0.56-0.80, p < .001) for overall survival (OS) and 0.70 (95% CI 0.61-0.79, p < .001) for progression-free survival (PFS), which strongly favored the addition of induction chemotherapy. The absolute 5-year survival benefits were 8.47% in OS and 10.27% in PFS, respectively. In addition, based on the available data of eight trials, induction chemotherapy showed significant efficacy in reducing locoregional failure rate (risk ratio [RR] = 0.81, 95% CI 0.68-0.96, p = .017) and distant metastasis rate (RR = 0.69, 95% CI 0.58-0.82, p < .001). CONCLUSION: This pairwise meta-analysis confirms the benefit in OS, PFS, and locoregional and distant controls associated with the addition of induction chemotherapy in nasopharyngeal carcinoma. IMPLICATIONS FOR PRACTICE: According to the results of this meta-analysis of ten trials, induction chemotherapy can prolong overall survival and progression-free survival and improve locoregional and distant controls for nasopharyngeal carcinoma.

Tumor location as an indication for adjuvant radiotherapy in pT3N0 rectal cancer after surgery.

BACKGROUND: The optimal care for pT3N0 rectal cancer remains controversial. And whether tumor location can be used to guide the administration of adjuvant radiotherapy for pT3N0 rectal cancer is not fully confirmed. The current study was designed to identify the benefit of adjuvant radiotherapy for pT3N0 rectal cancer. METHODS: We performed a retrospective study of 265 pT3N0 rectal cancer patients who were treated by surgery and adjuvant therapy from Mar. 2005 to Sept. 2015. All patients were divided into two groups according to receiving adjuvant radiotherapy or not. Overall survival (OS), disease-free survival (DFS) were compare between patients who did and did not receive adjuvant radiotherapy. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). RESULTS: For patients with lower tumor, DFS in adjuvant chemo-radiotherapy group was higher than that in adjuvant chemotherapy group. Besides, the rates of local recurrence and distant metastasis were found lower in patients who did receive adjuvant radiotherapy than those who did not. For patients with upper tumor, the 5-year OS and DFS were similar between groups of adjuvant chemotherapy and adjuvant chemo-radiotherapy. Multivariable analysis indicated both the CEA and tumor location were independent predictors of LRFS. And adjuvant radiotherapy predicted the DFS, LRFS and DMFS in lower rectal cancer patients. CONCLUSION: Tumor location can serve as an indication for the administration of adjuvant radiotherapy in pT3N0 rectal cancer patients.

Linc01638 Promotes Tumorigenesis in HER2+ Breast Cancer.

BACKGROUND: Long non-coding RNAs play crucial roles in various biological activities and diseases. The role of long intergenic non-coding RNA01638 (linc01638) in breast cancer, especially in HER2-positive breast cancer, remains largely unknown. OBJECTIVE: To investigate the effect of linc01638 on tumorigenesis in HER2-positive breast cancer. METHODS: We first used qRT-PCR to detect linc01638 expression in HER2-positive breast cancer cells and tissues. Then we analyzed the effects of linc01638 expression in HER2-positive breast cancer cells through cell apoptosis assay, cell proliferation assay, colony formation assay, and cell invasion assay. We conducted mouse xenograft model to further confirm the role of linc01638 in HER2-positive breast cancer. Moreover, we used Western blot and IHC analysis to access the effect of linc01638 on DNMTs, BRCA1 and PTEN expressions in transplanted tumors. RESULTS: Linc01638 was found to be remarkably overexpressed in HER2-positive breast cancer cells and tissues. Suppression of linc01638 enhanced cell apoptosis, as well as inhibited the growth and invasiveness of HER2-positive breast cancer cells in vitro and tumor progression and metastasis in vivo. Furthermore, inhibition of linc01638 by shRNA attenuated expression of DNMT1, DNMT3a, and DNMT3b, and promoted expression of BRCA1 and PTEN in HER2-positive breast cancer cells and mouse xenograft models. CONCLUSION: Linc01638 might be a promising biomarker and therapeutic target for treatment of HER2-positive breast cancer.

AFAP1-AS1 Promotes Epithelial-Mesenchymal Transition and Tumorigenesis Through Wnt/ß-Catenin Signaling Pathway in Triple-Negative Breast Cancer.

Long non-coding RNA (LncRNA) actin filament-associated protein1-antisense RNA 1 (AFAP1-AS1) is overexpressed in various types of cancers and plays an important role in tumor progression and prognosis. This study investigates the role of AFAP1-AS1 in tumor progression in triple-negative breast cancer (TNBC). We found that AFAP1-AS1 was overexpressed in TNBC tissues and cells. Overexpression of LncRNA AFAP1-AS1 was associated with poor prognosis in TNBC patients. Moreover, we demonstrated that upregulation of AFAP1-AS1 promoted cell proliferation and invasion, and inhibited cell apoptosis in vitro, while overexpression of AFAP1-AS1 promoted tumor growth in vivo. Our results also revealed that upregulation of AFAP1-AS1 activated Wnt/ß-catenin pathway to promote tumorigenesis and cell invasion by increasing the expression of C-myc and epithelial-mesenchymal transition-related molecules in TNBC. Collectively, AFAP1-AS1 can be an independent prognostic marker and an effective therapeutic target of triple- negative breast cancer.

The Selection of Time Interval Between Surgery and Adjuvant Therapy in Early Stage Cervical Cancer.

OBJECTIVES: The optimal interval between surgery and adjuvant treatment has not yet been found in cervical cancer. And whether patients with different FIGO stage should choose different interval is unknown. The purpose of this study was to evaluate whether interval has a different effect on oncologic outcome for patients with different tumor stages. METHODS: We performed a retrospective study of 226 cervical cancer patients who were treated by surgery and adjuvant therapy from May 2005 to August 2015. All patients were divided into 2 groups according to the interval of 5 weeks. Overall survival (OS) and disease-free survival (DFS) were compared between patients with interval shorter and longer than 5 weeks in the whole group and subgroups. Recurrence patterns were also analyzed. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival and distant metastasis-free survival for patients with stage IB2-IIA. RESULTS: For patients with stage IA2-IB1, the 5-year OS and DFS were similar between groups of short and long interval with also the comparable results of local and distant failure. For patients with IB2-IIA, both the OS and DFS in the short-interval group were higher than that in the long-interval group. Besides, the rates of local recurrence were found higher in the group of long interval compared with short interval. Multivariable analysis indicated that time interval was an independent predictor of DFS and local recurrence-free survival for patients with stage IB2-IIA. CONCLUSIONS: In cervical cancer patients, time interval between surgery and adjuvant therapy may have different effects on the prognosis in different FIGO stages.

Osteoradionecrosis of the Skull Base in Nasopharyngeal Carcinoma: Incidence and Risk Factors.

PURPOSE: Nasopharyngeal carcinoma (NPC) is a type of malignancy with a high prevalence in southern China and Southeast Asia. The primary treatment modality is radiation therapy (RT). Osteoradionecrosis (ORN) of the skull base remains one of the most serious complications after RT, affecting survival time and quality of life. Thus far, skull base ORN has been seldom reported and can be difficult to distinguish and easy to misdiagnose. In this retrospective study, we report the incidence of skull base ORN and analyze its associated factors in an attempt to decrease the occurrence of ORN. METHODS AND MATERIALS: From January 2001 to December 2012, a total of 1348 patients who received diagnoses of NPC received 1 course of RT. Complete medical records were reviewed, and the patients were examined by magnetic resonance imaging and nasopharyngeal endoscopy during follow-up after primary treatment. Patients with other tumors of the head and neck, a history of RT, failure to complete RT, and those lost to follow-up were excluded. Treatment was delivered with external beam RT using standard linear accelerators. RESULTS: A total of 1348 patients with NPC were enrolled in this study after 1 course of RT; among these patients, 14 received diagnoses of skull base ORN. The incidence of skull base ORN was 1.04%. The average latency interval from the completion of RT to the diagnosis of skull base ORN was 45.57 months. Skull base ORN after 1 course of RT was associated with the T stage; total radiation dose to the nasopharynx, including the skull base in the radiation field; and anemia. CONCLUSIONS: The occurrence of skull base ORN was associated with primary tumors with advanced T stages, high doses of nasopharynx RT, and radiation fields that included the skull base. These factors may be used as predictors for the incidence of skull base ORN.

circFBLIM1 act as a ceRNA to promote hepatocellular cancer progression by sponging miR-346.

BACKGROUD: Accumulating evidences indicate that circular RNAs (circRNAs), a class of non-coding RNAs, play important roles in tumorigenesis. However, the function of circRNAs in hepatocellular cancer (HCC) is largely unknown. METHODS: We performed circRNA microarrays to identify circRNAs that are aberrantly expressed in HCC tissues. Expression levels of a significantly upregulated circRNA, circFBLIM1, was detected by quantitative real-time PCR (qRT-PCR) in HCC cell lines and tissues. Then, we examined the functions of circFBLIM1 in HCC by cell proliferation, apoptosis, invasion and mouse xenograft assay. In addition, luciferase assay and RNA immunoprecipitation (RIP) assay were used to explore the miRNA sponge function of circFBLIM1 in HCC. RESULTS: Microarray analysis and qRT-PCR verified a circRNA termed circFBLIM1 that was upregulated in HCC tissues and cell lines. Knockdown of circFBLIM1 inhibited proliferation, invasion and promoted apoptosis in HCC. Via luciferase reporter assays, circFBLIM1 and FBLIM1 were observed to directly bind to miR-346. Subsequent experiments showed that circFBLIM1 and FBLIM1 regulated the expression of each other by sponging miR-346. CONCLUSIONS: Taken together, we conclude that circFBLIM1 may function as a competing endogenous RNA (ceRNA) to regulate FBLIM1 expression through sponging miR-346 to exert regulatory functions in HCC. circFBLIM1 may be a diagnostic biomarker and potential target for HCC therapy.

Tumor volume predicts local recurrence in early rectal cancer treated with radical resection: A retrospective observational study of 270 patients.

OBJECTIVE: Radical resection is regarded as the primary treatment for early rectal cancer, and tumor volume is an independent predictor of many other types of cancer. The purpose of the present study is to assess the effect of tumor volume on the survival of patients with early rectal cancer treated with radical surgery. METHODS: A total of 270 patients with histologically confirmed stage T1/2 N0 rectal cancer who underwent radical resection between September 2006 and September 2014 were enrolled in this study. The tumor volume was measured based on the preoperative pelvic MRI. The clinical significance of tumor volume with respect to patients' outcomes was evaluated, and the multivariate Cox proportional regression model was used to analyse the risk factors for survival of these patients. RESULTS: The median follow-up period was 57.6 months. The tumor volume was significantly correlated with preoperative Hb, CEA level and number of retrieved lymph nodes (all p < 0.05). The large tumor group had a lower disease-free survival (DFS) rate than the small tumor group (5-year DFS rate: 80.4% vs 89.6%, p = 0.042), whereas there was no difference in the overall survival rate. The 5-year local recurrence rates for patients in the large and small tumor groups were 10.5% and 3.0%, respectively (p = 0.030). Additionally, the tumor volume was an independent clinical predictor for both DFS and local recurrence-free survival (LRFS). CONCLUSION: In conclusion, the tumor volume is significantly associated with DFS and LRFS of patients with stage T1/2 N0 rectal cancer who underwent radical resection alone. Tumor volume may be considered an important indicator for neoadjuvant or adjuvant therapeutic interventions.

miR-29c contribute to glioma cells temozolomide sensitivity by targeting O6-methylguanine-DNA methyltransferases indirectely.

Temozolomide (TMZ) is the most commonly used alkylating agent in glioma chemotherapy. However growing resistance to TMZ remains a major challenge to clinicians. The DNA repair protein O6-methylguanine-DNA methytransferase (MGMT) plays critical roles in TMZ resistance. Promoter methylation can inhibit MGMT expression and increase chemosensitivity. Here, we described a novel mechanism regulating MGMT expression. We showed that miR-29c suppressed MGMT expression indirectly via targeting specificity protein 1 (Sp1). MiR-29c overexpression increased TMZ efficacy in cultured glioma cells and in mouse xenograft models. The miR-29c levels were positively correlated with patient outcomes. Our data suggest miR-29c may be potential therapeutic targets for glioma treatment.