Vaginal Transmission of Cancer from Mothers with Cervical Cancer to Infants.

Two cases of pediatric lung cancer (in 23-month-old and 6-year-old boys) resulting from mother-to-infant transmission of uterine cervical tumors were incidentally detected during routine next-generation sequencing of paired samples of tumor and normal tissue. Spontaneous regression of some lesions in the first child and slow growth of the tumor mass in the second child suggested the existence of alloimmune responses against the transmitted tumors. Immune checkpoint inhibitor therapy with nivolumab led to a strong regression of all remaining tumors in the first child. (Funded by the Japan Agency for Medical Research and Development and others; TOP-GEAR UMIN Clinical Trials Registry number, UMIN000011141.).

Therapeutic effect of dose-dense paclitaxel plus carboplatin with or without bevacizumab for Japanese patients with epithelial ovarian cancer.

BACKGROUND: Evidence regarding chemosensitivity to different therapeutic regimens in epithelial ovarian cancer (EOC) remains limited. This study aimed to investigate EOC implementation in daily clinical practice and reveal favorable regimens for EOC among Japanese patients. METHODS: We retrospectively collected clinical data of patients newly diagnosed with EOC from 2012 to 2021 at our affiliated institutions. We evaluated overall survival (OS) and progression-free survival (PFS) of conventional paclitaxel plus carboplatin (TC) vs. dose-dense TC (ddTC) according to the eligibility of GOG262 and JGOG3016 and those with bevacizumab (BEV) vs. without BEV based on GOG218. Further, we evaluated OS and PFS of ddTC and ddTC + BEV to TC + BEV among patients with stage III/IV. RESULTS: The ddTC group (n = 402) demonstrated longer PFS and OS than the TC group (n = 165) (adjusted hazard ratios [aHRs] [95% confidential intervals (CIs)]: 0.69 [0.55-0.88] and 0.67 [0.50-0.90], respectively). The group with BEV (n = 158) demonstrated a longer PFS than those without BEV (n = 296) (0.74 [0.57-0.95]), but not for OS (0.84 [0.60-1.17]). The ddTC and ddTC + BEV groups (n = 259 and 117) demonstrated no statistically significant differences in PFS and OS than the TC + BEV group (n = 75) (1.09 [0.79-1.50] and 0.74 [0.52-1.08] for PFS and 0.89 [0.59-1.34] and 0.73 [0.50-1.05] for OS, respectively). CONCLUSION: Our study may indicate ddTC, BEV, and their combination regimen as the promising first-line chemotherapy option among Japanese patients with advanced EOC.

Paclitaxel sensitizes homologous recombination-proficient ovarian cancer cells to PARP inhibitor via the CDK1/BRCA1 pathway.

OBJECTIVE: An effective treatment strategy for epithelial ovarian cancer (EOC) with homologous recombination (HR)-proficient (HRP) phenotype has not been established, although poly (ADP-ribose) polymerase inhibitors (PARPi) impact the disease course with HR-deficient (HRD) phenotype. Here, we aimed to clarify the cellular effects of paclitaxel (PTX) on the DNA damage response and the therapeutic application of PTX with PARPi in HRP ovarian cancer. METHODS: Two models with different PTX dosing schedules were established in HRP ovarian cancer OVISE cells. Growth inhibition and HR activity were analyzed in these models with or without PARPi. BRCA1 phosphorylation status was examined in OVISE cells by inhibiting CDK1, which was reduced by PTX treatment. CDK1 expression was evaluated in EOC patients treated with PTX-based neoadjuvant chemotherapy. RESULTS: PTX suppressed CDK1 expression resulting in impaired BRCA1 phosphorylation in OVISE cells. The reduced CDK1 activity by PTX could decrease HR activity in response to DNA damage and therefore increase the sensitivity to PARPi. Immunohistochemistry showed that CDK1 expression was attenuated in samples collected after PTX-based chemotherapy compared to those collected before chemotherapy. The decrease in CDK1 expression was greater with dose-dense PTX schedule than with the conventional PTX schedule. CONCULSIONS: PTX could act synergistically with PARPi in HRP ovarian cancer cells, suggesting that the combination of PTX with PARPi may be a novel treatment strategy extending the utility of PARPi to EOC. Our findings provide cules for future translational clinical trials evaluating the efficacy of PTX in combination with PARPi in HRP ovarian cancer.

Antenatal screening timeline and cutoff scores of the Edinburgh Postnatal Depression Scale for predicting postpartum depressive symptoms in healthy women: a prospective cohort study.

BACKGROUND: It is worthwhile to identify women at risk of developing postpartum depression during pregnancy. This study aimed to determine the optimal time and cutoff score for antenatal screening for prediction of postpartum depressive symptoms (PDS) using the Edinburgh Postnatal Depression Scale (EPDS) and to identify risk factors for PDS. METHODS: The target population was healthy pregnant women receiving antenatal care at a university hospital in Tokyo, Japan. During the first, second, and third trimesters, 3-4 days postpartum, and one month postpartum, they were asked to take the Japanese version of the EPDS questionnaire. The primary outcome of the study was PDS, defined as an EPDS score ≥ 9 at one month postpartum. The area under the receiver operating characteristics curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of EPDS scores at each antenatal screening time were calculated. RESULTS: From 139 pregnant women, 129 were successfully followed up throughout the study. The number of women with an EPDS score ≥ 9 during the first, second, and third trimesters, 3-4 days postpartum, and one month postpartum were 6/126 (4.8%), 9/124 (7.3%), 5/117 (4.3%), 17/123 (13.8%), and 15/123 (12.2%), respectively. Screening during the second trimester had the highest AUC to predict PDS (0.89) among antenatal screenings. The optimal EPDS cutoff score during the second trimester was 4/5 (sensitivity: 85.7%; specificity: 77.1%; PPV: 33.3%; NPV: 97.6%). An EPDS score ≥ 5 during the second trimester (adjusted odds ratio [aOR]: 15.9; 95% confidence interval [95%CI]: 3.2-78.1) and a family history of mental illness (aOR: 4.5; 95%CI: 1.2-17.5) were significantly associated with PDS. CONCLUSIONS: Our study suggests that the EPDS score at the second trimester with the cutoff value of 4/5 may be adequate for initial screening for prediction of PDS. Women with an EPDS score ≥ 5 at the second trimester require more elaborate follow-up.

Re-thinking the prognostic significance of positive peritoneal cytology in endometrial cancer.

BACKGROUND: Whether abnormal peritoneal cytology (PC) is an independent prognostic factor in endometrial cancer (EC) remains controversial. This study aimed to re-think the prognostic significance of PC in not only all EC patients but also in various subgroups with similar clinicopathological and biological characteristics. METHODS: EC patients who underwent primary surgery of at least a hysterectomy and were pathologically diagnosed with EC in four hospitals affiliated with the Jikei University School of Medicine were retrospectively reviewed. The prognostic significance of PC was evaluated with univariate and multivariate analyses in the entire cohort and subgroups stratified by surgical stages (early/advanced stages), tumor types (types 1/2), and risk classifications (low/intermediate/high). RESULTS: Of 1963 EC cases, 1616 met the inclusion criteria. Positive PC was identified as an adverse prognostic factor in analyses of all EC cases and in all subgroup analyses stratified by surgical stages and tumor types. In survival curve comparisons, the progression-free survival (PFS) and disease-specific survival in early-stage patients with positive PC were clearly located between those of stage II patients with negative PC and stage III patients. In the subgroup analyses stratified by risk classification in early-stage EC, positive PC was related to poorer PFS in the intermediate- and high-risk groups but not in the low-risk group. CONCLUSION: PC status was an independent prognostic factor of EC in all stages and tumor types. Early PC-positive cases, except for the low-risk group, may be recommended for upstaging and should be carefully managed compared with PC-negative cases.

A survey of Japanese interns to prepare for mandatory clinical training in obstetrics and gynecology.

AIM: Obstetrics and gynecology (Ob/Gyn) training became compulsory for Japanese physician interns from April 2020 to improve medical competence in treating women's diseases. This study aims to understand the Ob/Gyn training needs of postgraduate year 1-2 physicians (interns) and thereby improve training efficiency. METHODS: This study was administered to interns at Ob/Gyn training facilities from December 2019 to February 2020. An original questionnaire was used to evaluate their assessment of training needs. In analyses, interns were categorized according to whether they were willing to major in Ob/Gyn. RESULTS: Of the 1154 participants, 163 (14.1%) would major in Ob/Gyn (Ob/Gyn applicants) and 967 (83.8%) would not (non-Ob/Gyn applicants). At the time of the survey, 634 (54.9%) had rotated in Ob/Gyn, 253 (21.9%) planned to rotate, and 267 (23.1%) chose not to rotate. The two most favorable training experiences were "experience in surgical procedures" (81/141, 57.4%) and "wide treatment areas covered by Ob/Gyn" (78/141, 55.3%) among the Ob/Gyn applicants, and "specificity of women's treatment" (308/488, 63.1%) among the non-Ob/Gyn applicants. CONCLUSIONS: Ob/Gyn applicants and non-Ob/Gyn applicants differed in their assessment of Ob/Gyn rotations. It is crucial to provide medical training based on interns' needs to improve their skills for treating female patients.

A report on the 73th Annual Congress of the Japan Society of Obstetrics and Gynecology International Workshop for Junior Fellows: Risk-reducing surgery for hereditary breast and ovarian cancer.

At the 73rd Annual Congress of the Japan Society of Obstetrics and Gynecology, young doctors from Japan and South Korea made presentations on the present condition of risk-reducing surgery for hereditary breast and ovarian cancer (RRSO) in their respective country. RRSO was insured in Japan in April 2020, whereas in South Korea, it was insured 7 years earlier in 2013. In Japan, certification criteria have been set for facilities that perform RRSO, and the number of facilities is increasing, but regional disparities still exist in its distribution. The number of gBRCA1/2 testing facilities is larger, and the cost is more affordable in South Korea than in Japan. Additionally, South Korea provides genetic counseling to a wider range of relatives compared to Japan. In the future, as the indications for the gBRCA1/2 test have expanded as a companion diagnostic for the use of PARP inhibitors, it is expected that the number of candidates for the gBRCA1/2 mutation test and RRSO will increase in Japan. It is important to increase the number of BRCA tests while maintaining the quality of genetic counseling in order to provide adequate information on BRCA mutations and RRSO for patients to support their decision. For the development of hereditary breast and ovarian cancer (HBOC) medical care, it is necessary to publish a nationwide database in Japan and continue to analyze and discuss the data based on the results.

Initiatives and achievements of the Japanese Society of Obstetrics and Gynecology, Obstetrics and Gynecology MIRAI Committee 2020.

BACKGROUNDS: In 2013, the total number of obstetrician-gynecologists decreased. The Japanese Society of Obstetrics and Gynecology established the Obstetrics and Gynecology MIRAI Committee in 2015. Within the MIRAI Committee, Japanese Trainees in Obstetrics and Gynecology (JTOG) was established; it was comprised of 20 promising young obstetrician-gynecologists recommended from regions across Japan. The office term is 2 years. OBJECTIVE: The purpose of this report is to learn and inform about the results of MIRAI's activities. METHODS: We surveyed the trends in new obstetrician-gynecologists and also matched each seminar participant with them. RESULT: The number of new memberships has been increasing since the nadir in 2016. In particular, there are over 100 more new physicians specializing in the field in 2020 than there were at the nadir in 2016. It was revealed that approximately 50% of the participants in the summer school specialized in obstetrics and gynecology. Furthermore, approximately 70% of POP2 participants specialized in obstetrics and gynecology, which shows that these two recruitment seminars are extraordinarily effective events that result in an increase in the number of new obstetricians and gynecologists. CONCLUSION: We conclude that the activities of this MIRAI Committee and JTOG have been effective. With the spread of COVID-19 and the inability of obstetrician-gynecologists and students/clinical trainees to perform social distancing, it is currently difficult to hold hands-on seminars. However, we hope that new JTOG members will be able to create a new seminar format.

Analysis of risk factors for patients with early-stage cervical cancer: A study of 374 patients.

AIM: This study aimed to identify the postoperative histological features affecting the prognosis of patients with early-stage cervical cancer who underwent open radical hysterectomy. METHODS: This retrospective study enrolled 374 patients with pT1a, 1b1 and 2a1 early-stage cervical cancer who underwent open radical hysterectomy between 2001 and 2018. Survival outcomes were analyzed by Kaplan-Meier method and compared with log-rank test. Using the Cox proportional hazards regression test, we conducted a multivariate analysis for disease-free survival and overall survival. RESULTS: Others histology, including other epithelial tumors and neuroendocrine tumors, had a significantly worse prognosis in both disease-free survival and overall survival than those of squamous cell carcinoma and adenocarcinoma (hazard ratio, 4.37 and 11.76; P = 0.006 and P = 0.002, respectively), along with lymph node metastasis (hazard ratio, 2.99 and 7.03; P = 0.009 and P = 0.001, respectively). CONCLUSION: Others histology including adenosquamous carcinoma had a poor prognosis in early-stage cervical cancer as with high-risk factors.

Rethinking of treatment strategies and clinical management in ovarian clear cell carcinoma.

Ovarian clear cell carcinoma (OCCC), with unique clinical and molecular characteristics compared with other histological types of epithelial ovarian cancer (EOC), behaves like a distinct entity and has a poorer prognosis than other EOC types, especially in advanced stages. In addition, OCCC comprises approximately 27% of all EOC cases in Japan, compared with 12% in Western countries. Historically, patients with OCCC have been eligible for chemotherapeutic and surgical trials of EOC. It has been difficult to evaluate the specific impact of these trials on the prognosis of women with OCCC because of its rarity and unique molecular characteristics. Recent studies of OCCC revealed significant molecular variations related to carcinogenesis and molecular targets that could directly facilitate patient stratification and subsequent precision medicine. Thus, treatment strategies specific for OCCC based on its clinical and molecular characteristics are urgently needed. In this review, we highlight the management and treatment of OCCC from clinical aspects.

Prevention and practice during the COVID-19 emergency declaration period in Japanese obstetrical/gynecological facilities.

AIM: A nationwide questionnaire survey was performed to evaluate how Japanese Society of Obstetrics and Gynecology (JSOG) members dealt with the coronavirus disease (COVID-19) pandemic during the declared nationwide emergency. METHODS: We sent questionnaires to members of JSOG via official email. Participants answered anonymously using Google forms. RESULTS: Two (0.08%) JSOG members had contracted COVID-19. There was a clear decrease in the number of patients scheduled for operation, not only for malignant but also for benign diseases. A decrease in the number of outpatients for infertility treatment was also observed. Polymerase chain reaction testing for severe acute respiratory syndrome coronavirus 2 was available in 20.4% of the facilities. Inpatients and outpatients were requested to wear masks, limit the number of contacts and check body temperature when visiting hospitals/clinics. During parturition care, caregivers and physicians wore gloves, masks (other than N-95), face shields and gowns. About 66% and 80% of the facilities decided to transfer pregnant women if they had asymptomatic and symptomatic infection, respectively. Cesarean section was typically chosen as delivery mode in infected women. CONCLUSION: The COVID-19 pandemic provoked significant changes in obstetrics and gynecology practices in Japan. Apparently, nosocomial infections were largely prevented due to these changes, although some of them might not have been necessary.

Development and evaluation of a cervical cancer screening system in Cambodia: A collaborative project of the Cambodian Society of Gynecology and Obstetrics and Japan Society of Obstetrics and Gynecology.

AIM: In Cambodia, the Japan Society of Obstetrics and Gynecology and the Cambodian Society of Gynecology and Obstetrics have an on-going project, started in 2015, for cervical cancer prevention and treatment. The project, currently aimed at factory workers, includes a women's health education program that leads into cervical cancer prevention by establishment of a system for early detection and treatment. It begins by health education, screening for human papillomavirus (HPV), followed by colposcopy and quicker treatment of earlier precursor lesions. METHODS: Rates for participant screening, HPV test positivity, cervical intraepithelial neoplasia (CIN) detection and distribution of HPV types were compared between two screening programs, factory-based and hospital-based. Some HPV test samples were divided into two, one of which was sent to Japan for a quality-control check of the Cambodian testing. RESULTS: The factory-based participant screening rate was 19% (128/681). HPV was detected more frequently in the factory-based program participants (12%) than in the hospital-based program participants (5%). Unfortunately, however, the rate of receiving proper secondary colposcopy screening among the HPV-positive females was significantly higher in the hospital-based program (94%) than the factory-based program (40%) (P < 0.001). The Cambodian laboratory HPV testing accuracy was 92.6%. HPV types demonstrated no significant difference between the two prevention programs. CONCLUSION: We could successfully introduce HPV-based screening, starting from health education. However, low rate of screening, especially secondary screening for HPV positive factory workers was identified. Also, HPV testing could be further improved for accuracy through close monitoring.

Prognostic impact of interleukin-6 expression in stage I ovarian clear cell carcinoma.

OBJECTIVE: Ovarian clear cell carcinoma (OCCC) frequently presents at an early stage. In stage I OCCC, the prognosis differs according to substage. In particular, predictive biomarkers and new treatment strategies are needed for stage IC2/IC3 disease. We investigated tumor biology and prognostic factors for stage I OCCC from a clinicopathological perspective, including the expression of ARID1A and IL-6, which are considered critical for OCCC carcinogenesis. METHODS: A retrospective cohort study of 192 patients with stage I OCCC treated at a single institution was performed. We calculated overall survival (OS) with respect to 12 clinicopathological parameters that included the unique and diverse histological features of OCCC. RESULTS: The estimated 5-year OS rate in patients with all stage I OCCC was 88.9% during a median of 91months of follow-up. The multivariate analysis indicated that substage classification and IL-6 expression status were associated with poor OS (p=0.010 and p=0.027, respectively). Loss of ARID1A expression had no impact on survival; however, it was associated with substage (p=0.001), capsule rupture status (p=0.011), and ascites cytology (p=0.016). No clear association was found between ARID1A and IL-6 expressions. Histological findings, including the presence of endometriosis, adenofibroma, architectural pattern, and tumor cell type, showed no prognostic effects. CONCLUSIONS: Both substage classification and IL-6 expression status may be independent prognostic factors in stage I OCCC. Therefore, IL-6 molecular stratification may be crucial in optimizing therapeutic strategies for early stage OCCC to improve survival.

Antitumor effects of interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R) signaling pathway inhibition in clear cell carcinoma of the ovary.

Among epithelial ovarian cancers, clear cell carcinoma of the ovary (CCC) has unique clinical and molecular characteristics that include chemoresistance resulting in poor prognosis. It was shown that CCC recently was characterized by specific upregulation of the IL-6/IL-6R-signal transducer and activator of transcription 3 (Stat3) signaling pathway. In this study, we aim to clarify whether IL-6/IL-6R mediated signaling pathway could have clinical relations with CCC and to evaluate inhibitory effects of the pathway on CCC carcinogenesis. A total of 84 CCC cases collected from primary surgical specimens were evaluated by the immunohistochemical analysis for IL-6R and phosphorylated Stat3 (pStat3), and we found that high IL-6R expression correlated with poor patient survival both by the univariate and multivariate analyses, suggesting that IL-6/IL-6R signaling pathway could be implicated in the progression of CCC. We further investigated the effects of IL-6/IL-6R mediated signaling pathway inhibition either by IL-6R small interfering RNA (siRNA) approach or humanized anti-human IL-6R antibody (tocilizumab) in CCC. Inhibition of endogenous IL-6R including tocilizumab in CCC cells did reduce cell invasion ability and restored their response to cytotoxic reagent. These data suggest that IL-6/IL-6R signaling pathway could act on CCC cells to enhance invasion and chemoresistance and, therefore, targeting IL-6/IL-6R mediated signaling pathway could be a promising therapeutic strategy for CCC.

DYRK2 regulates epithelial-mesenchymal-transition and chemosensitivity through Snail degradation in ovarian serous adenocarcinoma.

Epithelial-mesenchymal-transition (EMT) plays essential roles in ovarian cancer invasion, metastasis, and drug resistance. A hallmark of EMT is the loss of E-cadherin, which is regulated by Snail. Recently, it was shown that dual-specificity tyrosine-regulated kinase 2 (DYRK2) controls Snail degradation in breast cancer. The aim of this study is to clarify whether DYRK2 regulates EMT through Snail degradation in ovarian serous adenocarcinoma (SA). Expression of DYRK2 and Snail in two pairs of cisplatin-resistant and the original cisplatin-sensitive ovarian cancer cell line were analyzed by immunoblotting and real-time RT-PCR analysis. Morphological change, invasion ability, and chemosensitivity were evaluated by using DYRK2 stable knockdown cell line in 2008 (2008 shDYRK2). Immunohistochemical analyses for DYRK2 and Snail were performed with surgical specimens. The correlations between the expression of these proteins and the clinicopathological parameters, including prognosis, were determined. Moreover, we conducted a hypodermic administration test in nude mice and examined reproductive and cisplatin response activities. DYRK2 protein expression was posttranslationally reduced in cisplatin-resistant SA cell lines. 2008 shDYRK2 showed mesenchymal phenotype and resistant to cisplatin. Immunohistochemistry demonstrated that DYRK2 expression inversely correlated with Snail expression, and reduced expression of DYRK2 was associated with shorter overall survival in SA. DYRK2 may regulate EMT through Snail degradation in ovarian SA and might be a predictive marker for a favorable prognosis in the treatment of this cancer.

Randomized controlled trial of enoxaparin versus intermittent pneumatic compression for venous thromboembolism prevention in Japanese surgical patients with gynecologic malignancy.

AIM: The aim of this study was to compare the efficacy and safety of enoxaparin and intermittent pneumatic compression (IPC) for venous thromboembolism (VTE) prevention in Japanese surgical patients with gynecologic malignancy. MATERIAL AND METHODS: Patients ≥ 40 years old undergoing major surgery for gynecologic malignancy without preoperative VTE were included. Written informed consent was obtained. Enrolled patients received IPC immediately before surgery. After surgery, they were randomly assigned to either an enoxaparin group or an IPC-alone group. The enoxaparin group received enoxaparin injection (20 mg, subcutaneous, every 12 h) from postoperative day 2 to 8. IPC was discontinued after the first injection. In the IPC-alone group, IPC was continued until full ambulation. The primary end-point was incidence of VTE, including pulmonary embolism and deep vein thrombosis, regardless of symptoms. An interim analysis was to be conducted when the first 30 patients had completed the study protocol. A Data and Safety Monitoring Board was established for making recommendation on the continuation or termination of the study based on the interim results. RESULTS: At the time of the interim analysis, six cases of VTE were found: five in the IPC-alone group and one in the enoxaparin group (Fisher's exact test, P = 0.08). Three patients in the IPC-alone group developed pulmonary embolism, but none in the enoxaparin group did so (Fisher's exact test, P = 0.10). The study was terminated following the Data and Safety Monitoring Board's recommendation. CONCLUSION: Enoxaparin might have lowered the risk of VTE among surgical patients with gynecologic malignancy. Further studies are necessary to confirm this.

MicroRNA-21 is a candidate driver gene for 17q23-25 amplification in ovarian clear cell carcinoma.

BACKGROUND: Epithelial ovarian cancer (EOC) is the most common cause of gynecological malignancy-related mortality. Ovarian clear cell carcinoma (CCC) has unique clinical characteristics and behaviors that differ from other histological types of EOC, including a frequent association with endometriosis and a highly chemoresistant nature, resulting in poor prognosis. However, factors underlying its malignant behavior are still poorly understood. Aberrant expression of microRNAs has been shown to be involved in oncogenesis, and microRNA-21 (miR-21) is frequently overexpressed in many types of cancers. The aim of this study was to investigate the role of miR-21 in 17q23-25 amplification associated with CCC oncogenesis. METHODS: We identified 17q23-25 copy number aberrations among 28 primary CCC tumors by using a comparative genomic hybridization method. Next, we measured expression levels of the candidate target genes, miR-21 and PPM1D, for 17q23-25 amplification by real-time RT-PCR analysis and compared those data with copy number status and clinicopathological features. In addition, immunohistochemical analysis of PTEN (a potential target of miR-21) was performed using the same primary CCC cases. We investigated the biological significance of miR-21 overexpression in CCC using a loss-of-function antisense approach. RESULTS: 17q23-25 amplification with both miR-21 overexpression and PTEN protein loss was detected in 4/28 CCC cases (14.2%). The patients with 17q23-25 amplification had significantly shorter progression-free and overall survival than those without 17q23-25 amplification (log-rank test: p = 0.0496; p = 0.0469, respectively). A significant correlation was observed between miR-21 overexpression and endometriosis. Both PTEN mRNA and PTEN protein expression were increased by miR-21 knockdown in CCC cells. We also confirmed that miR-21 directly bound to the 3'-untranslated region of PTEN mRNA using a dual-luciferase reporter assay. CONCLUSIONS: MiR-21 is a possible driver gene other than PPM1D for 17q23-25 amplification in CCC. Aberrant expression of miR-21 by chromosomal amplification might play an important role in CCC carcinogenesis through the regulation of the PTEN tumor suppressor gene.

Unique microRNA molecular profiles in lung cancer diagnosis and prognosis.

MicroRNA (miRNA) expression profiles for lung cancers were examined to investigate miRNA's involvement in lung carcinogenesis. miRNA microarray analysis identified statistical unique profiles, which could discriminate lung cancers from noncancerous lung tissues as well as molecular signatures that differ in tumor histology. miRNA expression profiles correlated with survival of lung adenocarcinomas, including those classified as disease stage I. High hsa-mir-155 and low hsa-let-7a-2 expression correlated with poor survival by univariate analysis as well as multivariate analysis for hsa-mir-155. The miRNA expression signature on outcome was confirmed by real-time RT-PCR analysis of precursor miRNAs and cross-validated with an independent set of adenocarcinomas. These results indicate that miRNA expression profiles are diagnostic and prognostic markers of lung cancer.