Comprehensive genetic analyses of childhood acute leukemia in Iraq using next-generation sequencing.

Background: Molecular analyses in hematological malignancies provide insights about genetic makeup. Probable etiological factors in leukemogenesis could also be disclosed. Since genetic analyses are still primitive in Iraq, a country of repeated wars, we conceived of performing next-generation sequencing (NGS), to disclose the genomic landscape of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) among a cohort of Iraqi children. Methods: Dried blood samples were collected from Iraqi children with ALL (n=55), or AML (n=11), and transferred to Japan where NGS was done. Whole-exome, whole-genome, and targeted gene sequencings were performed. Results: Somatic point mutations and the copy number variations among Iraqi children with acute leukemia were comparable with those in other countries, and cytosine-to-thymine nucleotide alterations were dominant. Strikingly, TCF3-PBX1 was the most recurrent fusion gene (22.4%) in B-cell precursor ALL (B-ALL), and acute promyelocytic leukemia (AML-M3) was subtyped in 5 AML cases. Additionally, a high frequency of RAS signaling pathway mutations was detected in children with B-ALL (38.8%), along with 3 AML cases that carried oncogenic RAS. Conclusions: Apart from disclosing the high frequency of TCF3-PBX1, NGS confirmed our previous finding of recurrent RAS mutations in Iraqi childhood acute leukemia. Our results suggest that the biology of Iraqi childhood acute leukemia is in part characteristic, where the war-aftermath environment or geography might play a role.

Eliciting a User's Preferences by the Self-Disclosure of Socially Assistive Robots in Local Households of Older Adults to Facilitate Verbal Human-Robot Interaction.

To realize a society in which older adults can live independently in their homes and familiar environments for as long as possible, their lives can be supported by providing appropriate technology. In this case, a new intervention for older people using socially assistive robots (SARs) is proposed; however, previous research has demonstrated that individual differences exist in the use and response to SAR interventions, and it has also been reported that SARs are not used by users in some cases. Therefore, in this study, we developed a self-disclosure function to promote continuous interaction with robots, using a Japanese corpus and self-disclosure items. In this study, we defined the specific requirements and functions of self-disclosure in SARs and developed ten non-arbitrary speech scripts from the field of social psychology using a Japanese corpus and self-disclosure items. To evaluate the effect of self-disclosure in SARs, an SAR was introduced to each household for 20 days, with the consent of seven community-dwelling older adults. Based on the recorded voice interaction data, we analyzed how the number, total time, and quality of verbal interactions changed with the SAR's self-disclosure. Furthermore, we conducted group interviews with the participants and received positive comments regarding the robot's self-disclosure. Some participants considered the specific personality of the SAR by accumulating its behavioral characteristics. As a consequence, these results indicate that the robot's self-disclosure feature is effective in significantly increasing the quantity and quality of verbal interactions with older adults.

[Automated Driving Cuts the Future].

There are strong expectations for automated driving. Whether the purpose is accident prevention or driver shortage, it is technically difficult to move fully automatically anywhere, and it is also difficult to establish business potential and merchantability through reasonable cost. In this paper, to properly understand automated driving, I will explain the current conditions and prospects.

A Study on Evaluations of Living Spaces by Caregivers for Elderly People.

Caregivers who provide nursing-care visits to the elderly learn to notice changes in the physical and mental functions of residents by looking for signs of disorder in living spaces and changes in the orderliness of living spaces. In this research, to understand what draws caregiver attention and how they evaluate them, 15 caregivers are interviewed and asked to evaluate images of 33 living spaces. The results show variances in evaluations concerning the degree of clutter of living spaces even among experienced caregivers, but that it is possible to classify the degree of clutter using a two-axis scale.

Design of a Behavior of Robot That Attracts the Interest of the Mildly Demented Elderly.

In this study, using the unexpected intervention overturning the interaction amount of the field and the mental model, an interaction of a robot system that enables sustained nonverbal communication with the mildly demented elderly was proposed and its effectiveness was shown in the group home of the mildly demented elderly.

Rapidly progressive Kaposi's Sarcoma in an Iraqi boy received Valproic acid: a case report and review of literature.

BACKGROUND: Kaposi's sarcoma (KS), an endothelial neoplasm, is associated with human herpes virus (HHV) -8 infection. KS has four clinical sub-types: Mediterranean/classic, African/endemic, human immunodeficiency virus (HIV) -associated/epidemic, and transplantation-related/iatrogenic. Immunosuppression is an important cofactor in KS process. Classic KS (CKS) is exceedingly rare in children and when occurs, it is much more disseminated than adults. The epidemic, HIV-associated and the iatrogenic forms of childhood KS are a result of a profound and acquired T-cell deficiency. To our knowledge, this is the first paediatric KS case report from Iraq. Our patient was showing an unusual aggressive course of the disease while receiving Valproic acid (VPA) of the potential immune-suppressive effect. CASE PRESENTATION: A six-year-old Iraqi boy, who had cerebral palsy (CP) and epilepsy since the age of 9-months, had received VPA to control his seizures. He developed skin discoloration followed by nodules that disseminated proximally from the lower extremities to the groin, face, ears and oral cavity, and then he died from severe respiratory distress after 110 days from the disease evolution. KS diagnosis was proved by a skin biopsy. As the patient was of Arab-Asian ethnicity and was HIV-seronegative status, accordingly, his condition best fitted the classic form of KS. However, recent studies showed the link of VPA with the reactivation of HHV-8. Moreover, accumulated experimental and clinical data elucidated that VPA induces T-cell suppression. Given that there was a lack of facilities to perform the laboratory immunological diagnostic tests in Iraq, the VPA-induced effect on immunity in our case (iatrogenic KS) could not be evaluated. CONCLUSIONS: Our report demonstrates a rare, rapidly progressing paediatric KS case and highlights the possible role of the 5-years' administration of VPA and its challenging effect on cellular immunity based on recent studies. Thus, VPA could have promoted the development of the KS in our patient. This report also recalls the need of paediatricians to consider KS especially when the skin lesion appears at the child's foot even in countries outside the geographical map of the disease.

Analysis of KRAS and NRAS Gene Mutations in Arab Asian Children With Acute Leukemia: High Frequency of RAS Mutations in Acute Lymphoblastic Leukemia.

BACKGROUND: KRAS and NRAS gene mutations are frequently observed in childhood leukemia. The objective of this study was to determine the frequency of RAS mutations and the association between RAS mutations and other genetic aberrations in Arab Asian children with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). METHODS: Diagnostic samples of 485 patients (<18 years) with acute leukemia from Iraq and Jordan were obtained, using Flinders Technology Associates filter papers. Polymerase chain reaction and direct sequencing were performed in Japan. RESULTS: RAS mutations were detected in 86/318 (27%) of ALL cases and 35/167 (21%) of AML cases. The frequency of NRAS mutation was similar to that of KRAS mutation in ALL. Two RAS mutations were detected in nine patients. Among 264 Iraqi patients with ALL, RAS mutation was significantly associated with lower initial white blood cell count. Of 57 patients with chimeric transcripts, only two patients with either TEL-AML1 or E2A-PBX1 had KRAS mutation. The frequency of NRAS mutation was four times higher than that of KRAS mutation in AML. FAB-M4 and M5 subsets were associated with RAS mutation. Among 134 Iraqi patients with AML, 18 patients had RAS mutations and other genetic aberrations. In particular, 9 of 25 (36%) with MLL-rearrangement had RAS mutations. CONCLUSION: The prevalence of oncogenic RAS mutations was higher among Arab Asian children than in other countries. RAS mutations in AML were found to coexist with other genetic aberrations, particularly MLL rearrangement.

Frequent coexistence of RAS mutations in RUNX1-mutated acute myeloid leukemia in Arab Asian children.

BACKGROUND: RUNX1 mutation plays an important role in adult leukemic transformation. However, its contribution to the development of childhood leukemia remains unclear. In the present study, we analyzed point mutations of RUNX1 gene in children and adolescents with acute myeloid leukemia (AML) from Iraq and Jordan. PROCEDURE: Bone marrow and/or peripheral blood samples were collected from 178 patients of Arab Asian ethnicity (aged ≤17 years) newly diagnosed with AML: 145 samples from Iraq and 33 samples from Jordan. Direct DNA sequencing was performed on six genes including RUNX1 gene (exons 3-8). RESULTS: RUNX1 point mutations were identified in 10 (5.6%) of 178 patients. One patient possessed biallelic mutations of RUNX1 gene. C-terminal area was the predominant site of RUNX1 mutations (eight in C-terminal and two in N-terminal). Patients with RUNX1 mutations were significantly older than those with wild-type of the gene. Additionally, AML M0 subtype was more frequently found in patients with RUNX1 mutations. Both RUNX1 mutations and RAS mutations were identified in 4 of 10 children. Three patients with RUNX1 mutation had FLT3-ITD. On the other hand, 36 (21.4%) and 25 (14.9%) of 168 patients with wild-type of the gene had a RAS mutation and FLT3-ITD, respectively. Eight of 10 patients with RUNX1 mutations died of hematological relapse. CONCLUSION: The incidence of RUNX1 mutations in Arab Asian children and adolescents with AML was 5.6%. Further studies are required to clarify whether RAS mutations contribute to the development of pediatric AML associated with RUNX1 mutations.

Analysis of class I and II aberrations in Iraqi childhood acute myeloid leukemia using filter paper cards.

The lack of molecular diagnosis in the field of cancer in Iraq has motivated us to perform a genetic analysis of pediatric acute myelogenous leukemia (AML), including class I and II aberrations. Peripheral blood or bone marrow cells were collected from 134 AML children aged ≤15 years. Flinders Technology Associates (FTA) filter paper cards were used to transfer dried blood samples from five Iraqi hospitals to Japan. DNA sequencing was performed to identify class I mutations. Nested RT-PCR was used to detect class II aberrations, except that MLL rearrangement was detected according to long distance inverse-PCR. NPM1 and FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations were analyzed by GeneScan using DNA template. Among 134 Iraqi pediatric AML samples, the most prevalent FAB subtype was M2 (33.6 %) followed by M3 (17.9 %). Class I mutations: 20 (14.9 %), 8 (6.0 %), and 8 (6.0 %) patients had FLT3-ITD, FLT3-TKD, and KIT mutations, respectively. Class II mutations: 24 (17.9 %), 19 (14.2 %), and 9 (6.7 %) children had PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 transcripts, respectively. MLL rearrangements were detected in 25 (18.7 %) patients. NPM1 mutation was detected in seven (5.2 %) cases. Collectively, approximately 30 % of AML children were proved to carry favorable prognostic genetic abnormalities, whereas approximately 10 % had high FLT3-ITD allelic burden and needed a special treatment plan including allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) was frequent among Iraqi pediatric AML. It is likely that molecular diagnosis using FTA cards in underdeveloped countries could guide doctors towards an appropriate treatment strategy.

Priorities of health care outcomes for the elderly.

OBJECTIVES: Physicians are uncertain about what medical services should be provided to older and/or disabled patients. Better understanding of health outcome prioritization among health care providers and recipients may help the process of decision- and policy-making. For this purpose, surveys were conducted on priorities of health care outcomes for the elderly. DESIGN: Survey research. SETTING: Four groups of health care providers and four groups of health care recipients. PARTICIPANTS: A total of 2512 health care providers and 4277 recipients. MEASUREMENTS: Questionnaires were sent to more than 8000 health care providers and more than 9000 health care recipients: geriatricians, physicians who commonly see older patients or work in long term care facilities, staff members and participants in adult day care, patients in outpatient geriatric clinics, family members of patients with dementia, and community-dwelling older adults. The questionnaire asked the subjects to rank 12 measures of health care outcomes. RESULTS: The mean response rate was 49%. All health care provider groups considered "improvement of quality of life" the most important. In contrast, in health care recipient groups, "effective treatment of illness," "improvement of physical function," and "reduction of carer burden" were given high priority, whereas "improvement of quality of life" was perceived as less important. All the groups, including health care providers and recipients, ranked "reduction of mortality" the least important, followed by "avoiding institutional care." Stratification analysis showed that the results did not differ by sex, nursing care level, or the existence of relatives who required nursing care, whereas age slightly influenced the order of high-ranked measures. CONCLUSION: Priorities of health care services and their differences between providers and recipients should be taken into account in the health care of older patients and the design of health care policies and research.

Serum concentration of fentanyl during conversion from intravenous to transdermal administration to patients with chronic cancer pain.

BACKGROUND: To the best of our knowledge, there have been no reports on the pharmacokinetics and pharmacodynamics during the conversion from continuous intravenous infusion (CII) to transdermal fentanyl administration. The primary objective of the present study was to clarify the pharmacokinetic characteristics during this conversion. A secondary objective was to identify an association between serum albumin and the absorption of fentanyl from the transdermal patch. METHODS: A prospective study was conducted from February 2010 to August 2011 that enrolled 19 patients with chronic cancer pain. Patients were classified into 2 study groups according to body mass index and albumin level. All patients received the conversion from CII to transdermal fentanyl using a 2-step taper of CII over 6 hours. Comparisons of efficacy, toxicity, and serum fentanyl concentrations between study groups were analyzed at baseline, 3, 6, 9, 12, 15, 18, and 24 hours after initiation of the conversion. RESULTS: The dose-adjusted serum fentanyl concentrations for all patients were significantly decreased at 15 to 24 hours after conversion compared with baseline, although pain intensity and the number of rescue events remained stable during the conversion. The dose-adjusted serum fentanyl concentrations at 9 to 24 hours were significantly reduced in the low albumin group compared with the normal albumin group (P<0.05). CONCLUSIONS: Our study demonstrated that the dose-adjusted serum fentanyl concentrations remained relatively stable, and pain intensity and the number of rescue events remained stable during conversion. Hypoalbuminemia was strongly associated with poor absorption of transdermally administered fentanyl.

[A new attempt to promote home medical care in Kashiwa city-usefulness of information and communication technology with seamless multidisciplinary cooperation].

Due to the rapidly increasing super-aging society, medical policy in Japan should be redefined. Therefore, the medical and nursing home care system should now be revised greatly. We need to change the current principle that is based on cure only. The patients should receive hospitable care closely connected with their life in their home-town(region)throughout their lifetime. This is termed as "home medical care system". Here, we promote patient-centered medical home care, which implements the chronic and/or End-Of-Life care models, in Kashiwa city, Chiba prefecture. This system is a promising framework for primary care transformation. There is a need for a multidisciplinary team-based care system using information and communication technology(ICT)with smooth and seamless cooperation. However, increased awareness among the workers engaged in home medical care is first required.

Recursive partitioning analysis for new classification of patients with esophageal cancer treated by chemoradiotherapy.

BACKGROUND: The 7th edition of the American Joint Committee on Cancer staging system does not include lymph node size in the guidelines for staging patients with esophageal cancer. The objectives of this study were to determine the prognostic impact of the maximum metastatic lymph node diameter (ND) on survival and to develop and validate a new staging system for patients with esophageal squamous cell cancer who were treated with definitive chemoradiotherapy (CRT). METHODS: Information on 402 patients with esophageal cancer undergoing CRT at two institutions was reviewed. Univariate and multivariate analyses of data from one institution were used to assess the impact of clinical factors on survival, and recursive partitioning analysis was performed to develop the new staging classification. To assess its clinical utility, the new classification was validated using data from the second institution. RESULTS: By multivariate analysis, gender, T, N, and ND stages were independently and significantly associated with survival (p < 0.05). The resulting new staging classification was based on the T and ND. The four new stages led to good separation of survival curves in both the developmental and validation datasets (p < 0.05). CONCLUSIONS: Our results showed that lymph node size is a strong independent prognostic factor and that the new staging system, which incorporated lymph node size, provided good prognostic power, and discriminated effectively for patients with esophageal cancer undergoing CRT.

Genetic evaluation of childhood acute lymphoblastic leukemia in Iraq using FTA cards.

BACKGROUND: Genetic examination of childhood leukemia has not been available in Iraq. We here report the frequency of TEL-AML1, E2A-PBX1, MLL-AF4, and BCR-ABL chimeric transcripts in 264 Iraqi children newly diagnosed with acute lymphoblastic leukemia (ALL), using FTA cards impregnated with bone marrow aspirate or whole blood. PATIENTS AND METHODS: The diagnosis of ALL was made according to standard French-American-British morphologic criteria. Based on the results of storage temperature and duration, most of the FTA samples were preserved at 4°C for up to 6 weeks in five Iraqi hospitals and then transferred to Japan for molecular analysis. Nested reverse transcription-polymerase chain reaction was adopted for the analysis. RESULTS: TEL-AML1 chimeric transcript product was found in 32 (12.1%) of 264 ALL patients. Eleven (4.2%) patients, 4 (1.5%) patients, and 11 (4.2%) patients had E2A-PBX1 mRNA, MLL-AF4 mRNA, and BCR-ABL mRNA, respectively. One patient had both TEL-AML1 and E2A-PBX1 fusion genes. The incidence of TEL-AML1 in Iraqi ALL children appears to be similar to or slightly higher than those of Jordan (12%) and Kuwait (7%). The prevalence and clinical findings of ALL patients with either E2A-PBX1 or BCR-ABL were comparable to the data reported elsewhere. CONCLUSION: International collaboration via FTA cards may be helpful to improve diagnosis and management of patients with hematological malignancies in low-income and underdeveloped countries.

Interactions of household composition and required care level with functional and cognitive status among disabled Japanese elderly living in a suburban apartment complex.

AIM: In the forthcoming super-aging society, the appropriate assessment of functional and cognitive conditions of disabled elderly people will become increasingly significant in providing care services. Care level and household composition would be key factors to assess function. There might also be an interaction between the two factors with the function. The present study examined the associations of household composition and care level with functional and cognitive status among the disabled elderly living in a suburban apartment complex with a high rate of aged residents (39% in 2009). METHODS: Participants were 190 disabled elderly persons aged 65 years and over who lived in the apartment complex. Cross-sectional data were collected between May 2009 and August 2010, including care level, household composition, basic activities of daily living (BADL), instrumental activities of daily living (IADL) and the independence level in relation to cognitive status. Lower scores meant less independence in BADL and IADL, and as determined by the cognitive/independence scale. RESULTS: Approximately half of the participants lived alone. Generalized linear model procedure showed significant interactions with the BADL score and cognitive/independence scale between household composition and care level. Scores for BADL and the cognitive/independence scale in groups receiving a higher care level were lower; however, the slope of the trend for the elderly living alone was more gradual than for the elderly living with others. CONCLUSION: It is important for health-care providers to assess in detail the status of the disabled elderly considering both their household composition and care level in planning and providing assistance for them.

Neo-adjuvant chemoradiation therapy using S-1 followed by surgical resection in patients with pancreatic cancer.

OBJECTIVE: The aim of this study was to compare short-term surgical results in pancreatic cancer patients who underwent surgical resection after neo-adjuvant chemoradiation therapy (NACRT) using S-1. METHODS: The study population comprised 77 patients with pancreatic cancer between 2006 and 2010. Out of 34 patients who underwent staging laparoscopy between 2008 and 2010, 31 patients without occult distant organ metastasis underwent chemoradiation and of whom 30 underwent pancreatectomy (NACRT group). Of the other 43 patients, 36 underwent surgical resection in 2006-2008, followed by adjuvant therapy (adjuvant group). The primary endpoint was frequency of pathological curative resection (R0). RESULTS: The new regimen of NACRT was feasible and safe. Twenty-eight of 30 (93%) patients in the NACRT group had R0 resection, which was significantly higher than in the adjuvant group (21 of 36 patients, 58%, p = 0.005). The number and extent of metastatic lymph nodes in the NACRT group (1 (0-25), N0/1; 18 of 38) was significantly lower than in the adjuvant group (2 (0-19), N0/1; 23 of 30), p = 0.0363). The frequency of intractable ascites in the NACRT group (eight of 30) was significantly higher than in the adjuvant group (two of 36, p = 0.035). CONCLUSION: Neo-adjuvant chemoradiation therapy using S-1 followed by pancreatectomy can improve the rate of pathologically curative resection and reduces the number and extent of lymph node metastasis.

Six- versus 12-h conversion method from intravenous to transdermal fentanyl in chronic cancer pain: a randomized study.

PURPOSE: The objective of the present prospective study was to compare the safety and efficacy of a 12-h method to a 6-h method in chronic cancer pain management. MATERIALS AND METHODS: Randomized, prospective clinical trial was conducted between December 2007 and June 2009, enrolling 90 patients with chronic cancer pain. Patients with chronic cancer pain were randomly assigned to the conversion from continuous intravenous infusion to transdermal fentanyl using two-step taper of the continuous intravenous infusion in 12 h (12-h method) or the conversion in 6 h (6-h method). The parameters assessed in the present study included pain intensity (on a scale of 0 to 10) and bolus use frequency, and the adverse effects were assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 3. RESULTS: Pain intensity and the number of boluses during conversion remained stable in both arms. The incidence of adverse events was 25.6% in the 12-h method group and 2.3% in the 6-h method group (95% confidence interval, 0.01-0.55; p = 0.002). Adverse events occurred in four patients at 6-12 h, five patients at 12-18 h, two patients at 18-24 h, and one patient at 24-48 h after application. CONCLUSIONS: Excellent safety profile and sustained efficacy are shown for the 6-h conversion method.

Asymptomatic paradoxical and symptomatic pulmonary air embolism during central venous catheter insertion.

A 65-year-old man developed respiratory distress during insertion of a central venous catheter (CVC). The presence of gas in the pulmonary trunk and ascending aorta was observed on computed tomography (CT) scans performed immediately after insertion, and paradoxical air embolism (PAE) was diagnosed. There were no symptoms of cerebral or coronary arterial embolism, and the patient was maintained in the same supine position as during CVC insertion. CT conducted after 200 min confirmed disappearance of the gas, and the resting position was discontinued. No subsequent symptoms of PAE occurred. In this patient with respiratory distress during CVC insertion, CT revealed PAE, and PAE was resolved and systemic arterial embolism did not occur by maintenance of the supine position and O(2) administration. This case also highlights the potential risk for the occurrence of asymptomatic PAE related to CVC insertion.

Radiological response and clinical outcome in patients with femoral bone metastases after radiotherapy.

We evaluated the radiological response and clinical outcome in patients with femoral bone metastases after radiotherapy. 102 consecutive patients with femoral metastases without pathological fracture were treated by surgery or radiotherapy between 2002 and 2005. Twelve of them initially treated with surgery were excluded from this study. The remaining 90 patients with 102 lesions underwent radiation therapy as the initial treatment. Twelve patients who died within 30 days by disease progression and 6 who were lost to follow-up were excluded. The remaining 72 patients with 84 lesions including 43 impending fractures were enrolled in this analysis. Radiological changes were categorized into complete response, partial response, no change, and progressive disease based on plain radiograph findings. Pain relief was reviewed for 77 painful lesions. The median radiation dose was 30 Gy. No re-irradiation was performed. 35 lesions (42%) achieved radiological responses median 3 months after radiotherapy. Pain relief was obtained in 36 of 77 lesions (47%). There was no significant correlation between radiological response and pain relief (P = 0.166). Eleven lesions eventually required surgery and considered as treatment failure. The treatment failure rate in the radiological progressive disease (PD) group (8/19, 42%) was significantly higher than that in the non-PD group (3/65, 5%) (P < 0.001). Among 43 impending fracture lesions, 15 lesions (36%) experienced radiological response and 35 lesions (81%) required no surgical interventions. Our data suggest that radiotherapy can enable metastatic bone healing and avoid surgery in many lesions. However, radiological PD lesions often require surgery after radiotherapy.

Identification of genes associated with progression and metastasis of advanced cervical cancers after radiotherapy by cDNA microarray analysis.

PURPOSE: To identify a set of genes related to the progression and metastasis of advanced cervical cancer after radiotherapy and to establish a predictive method. METHODS AND MATERIALS: A total of 28 patients with cervical cancer (15 stage IIIB, 13 stage IVA patients) who underwent definitive radiotherapy between May 1995 and April 2001 were included in this study. All patients were positive for human papillomavirus infection and harbored the wild-type p53 gene. The expression profiles of 14 tumors with local failure and multiple distant metastasis and 14 tumors without metastasis (cancer free) obtained by punch biopsy were compared before treatment, using a cDNA microarray consisting of 23,040 human genes. RESULTS: Sixty-three genes were selected on the basis of a clustering analysis, and the validity of these genes was confirmed using a cross-validation test. The most accurate prediction was achieved for 63 genes (sensitivity, 78.8%; specificity, 38.1%). Some of these genes were already known to be associated with metastasis via chromosomal instability (TTK, BUB1B), extracellular matrix components (matrix metalloproteinase 1 [MMP-1]), and carcinogenesis (protein phosphatase 1 regulatory subunit 7 [PPP1R7]). A "predictive score" system was developed that could predict the probability for development of metastases using leave-one-out cross-validation methods. CONCLUSIONS: The present results may provide valuable information for identified predictive markers and novel therapeutic target molecules for progression and metastasis of advanced cervical cancer.