Association between the methylation of CpG islands in JAK-STAT pathway-related genes and colorectal cancer.

BACKGROUND: Aberrant promoter methylation of CpG islands plays an important role in carcinogenesis. However, the association between the DNA methylation of JAK-STAT pathway-related genes in peripheral blood leukocytes and colorectal cancer (CRC) susceptibility remains unclear. METHODS: We conducted a case-control study of 403 patients with CRC and 419 cancer free controls, and the DNA methylation levels of JAK2, STAT1, STAT3, and SOCS3 in peripheral blood samples from all subjects were assessed using a methylation-sensitive high-resolution melting (MS-HRM) analysis. RESULTS: Compared with controls, the methylation of the JAK2, STAT1 and SOCS3 genes increased the CRC risk (ORadjusted=1.96, 95% CI, 1.12-3.41, P=0.01; ORadjusted=5.37, 95% CI, 3.74-7.71, P<0.01; ORadjusted=3.30, 95% CI, 1.58-6.87, P<0.01). In the multiple CpG site methylation (MCSM) analysis, a high MCSM value denoted an increased CRC risk (ORadjusted=4.97, 95% CI, 3.34-7.37, P<0.01). CONCLUSION: In peripheral blood, the methylation of JAK2, STAT1, and high levels of MCSM are promising biomarkers for CRC risk.

CHST7 Gene Methylation and Sex-Specific Effects on Colorectal Cancer Risk.

BACKGROUND: X chromosome aberrations are involved in carcinogenesis and are associated with gender differences in cancer development. Abnormal DNA methylation also contributes to cancer. Carbohydrate Sulfotransferase 7 (CHST7), encoded by the X chromosome, is abnormally expressed during tumor development. However, its impact on colorectal cancer (CRC) and the effect of CHST7 methylation on sex-specific CRC risk remain unclear. AIMS: To investigate the effect of CHST7 methylation in white blood cells on CRC risk and to evaluate its impact on gender-specific differences. METHODS: CHST7 methylation in white blood cells was determined using methylation-sensitive high-resolution melting. A propensity score analysis was performed to control potential confounders. Furthermore, extensive sensitivity analyses were applied to assess the robustness of our findings. In addition, we validated the initial findings with a GEO dataset (GSE51032). RESULTS: CHST7 hypermethylation in white blood cells was associated with an increased CRC risk [odds ratio (OR)adj = 4.447, 95% confidence interval (CI) 2.662-7.430; p < 0.001]. The association was validated with the GEO dataset (ORadj = 2.802, 95% CI 1.235-6.360; p = 0.014). In particular, CHST7 hypermethylation significantly increased the CRC risk in females (ORadj = 7.704, 95% CI 4.222-14.058; p < 0.001) and younger patients (≤ 60 years) (ORadj = 5.755, 95% CI 2.540-13.038; p < 0.001). Subgroup analyses by tumor location and Duke's stage also observed these associations. CONCLUSION: CHST7 methylation in white blood cells is positively associated with CRC risk, especially in females, and may potentially serve as a blood-based predictive biomarker for CRC risk.

Cyclic adenosine phosphate improves functional recovery after spinal cord injury via activating unfolded protein response.

The current study aimed to evaluate the role and underlying mechanism of cyclic adenosine phosphate (cAMP) on the functional recovery of spinal cord injury (SCI). Basso, Beattie and Bresnahan (BBB) scoring and inclined plane test indicated that cAMP treatment improved the functional recovery of SCI rats. Real time PCR and western blot analysis showed the mRNA and protein levels of IRE1, PERK, and ATF6 were increased in the SCI rats than those of sham control. However, higher levels of IRE1, PERK, and ATF6 were indicated after cAMP treatment. Meanwhile, more apoptotic cells were observed in the SCI rats, as evidenced by TUNEL staining and increased expression of GRP78, CHOP, and caspase12. In contrast, the expression of GRP78, CHOP, and caspase12 was decreased in SCI rats after cAMP treatment. In summary, we showed novel data that cAMP reduced cell apoptosis and functional recover after SCI mainly via activating UPR.

Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the symptomatic effectiveness and safety of oral symptomatic slow-acting drugs (SYSADOAs) on the treatment of knee and/or hip osteoarthritis, such as chondroitin, glucosamine, and combination treatment with chondroitin plus glucosamine. METHODS: We searched electronic database including PubMed, Embase, Cochrane Library, and the reference lists of relevant articles published from inception to May 22, 2018. An updated meta-analysis was performed to assess the effectiveness of these slow-acting drugs for osteoarthritis. RESULTS: Twenty-six articles describing 30 trials met our inclusion criteria and were included in the meta-analysis. The estimates between chondroitin and placebo showed that chondroitin could alleviate pain symptoms and improve function. Compared with placebo, glucosamine proved significant effect only on stiffness improvement. However, the combination therapy did not have enough evidence to be superior to placebo. Additionally, there was no significant difference in the incidence of AEs and discontinuations of AEs when compared with placebo. CONCLUSIONS: Given the effectiveness of these symptomatic slow-acting drugs, oral chondroitin is more effective than placebo on relieving pain and improving physical function. Glucosamine showed effect on stiffness outcome. Regarding on the limited number of combination therapy, further studies need to investigate the accurate effectiveness. This information accompanied with the tolerability and economic costs of included treatments would be conducive to making decisions for clinicians.

Multiple gene-specific DNA methylation in blood leukocytes and colorectal cancer risk: a case-control study in China.

The relationship between gene-specific DNA methylation in peripheral blood leukocytes and colorectal cancer (CRC) susceptibility is unclear. In this case-control study, the methylation status of a panel of 10 CRC-related genes in 428 CRC cases and 428 cancer-free controls were detected with methylation-sensitive high-resolution melting analysis. We calculated a weighted methylation risk score (MRS) that comprehensively combined the methylation status of the panel of 10 genes and found that the MRS_10 was significantly associated with CRC risk. Compared with MRS-Low group, MRS-High group and MRS-Medium group exhibited a 6.51-fold (95% CI, 3.77-11.27) and 3.85-fold (95% CI, 2.72-5.45) increased risk of CRC, respectively. Moreover, the CRC risk increased with increasing MRS_10 (Ptrend < 0.0001). Stratified analyses demonstrated that the significant association retained in both men and women, younger and older, and normal weight or underweight and overweight or obese subjects. The area under the receiver operating characteristic curves for the MRS_10 model was 69.04% (95% CI, 65.57-72.66%) and the combined EF and MRS_10 model yielded an AUC of 79.12% (95% CI, 76.22-82.15%). Together, the panel of 10 gene-specific DNA methylation in leukocytes was strongly associated with the risk of CRC and might be a useful marker of susceptibility for CRC.

Strong association of the polymorphisms in PBEF1 and knee OA risk: a two-stage population-based study in China.

The association of Pre-B cell colony enhancing factor 1 (PBEF1) with obesity, together with its pro-inflammatory properties suggests that PBEF1 might be another crucial mediator that links inflammation with obesity and primary osteoarthritis (OA). We hypothesized that polymorphisms in PBEF1 may modify the risk of developing OA. Thus we systematically screened 4 tagging polymorphisms (rs4730153, rs2058540, rs3801267 and rs16872158) in PBEF1 and evaluated the association between the genetic variants and OA risk in a two-stage case-control study including 196 cases and 442 controls in the first stage and 143 cases and 238 controls in the second stage. In the first stage, two SNPs (rs4730153 and rs16872158) were found to be potentially associated with OA risk (P < 0.05), which were further confirmed in the second stage with similar effects. After combining the two stages, we found that rs4730153 was significantly associated with decreased risk of OA in an additive genetic model (P < 0.05), while rs16872158 showed increased risk of developing OA (P < 0.05). Combined analysis of these 2 SNPs showed a significant allele-dosage association between the number of risk alleles and OA risk (Ptrend = 5.25 × 10(-5)). These findings indicate that genetic variants in PBEF1 gene may modify individual susceptibility to OA in the Chinese population.

Association between co-inhibitory molecule gene tagging single nucleotide polymorphisms and the risk of colorectal cancer in Chinese.

PURPOSE: T lymphocyte immune responses are controlled by both co-stimulatory and co-inhibitory signaling through T cell co-receptors. Cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death 1 (PD-1) and B and T lymphocyte attenuator (BTLA) are all co-inhibitory molecules that negatively regulate the activation of T cells. In this study, we investigated the relationship between ten tagging SNPs in three co-inhibitory molecule genes and colorectal cancer (CRC). METHODS: We conducted a hospital-based case-control study consisting of 601 cases with CRC and 627 CRC-free individuals from the Heilongjiang Province of China. RESULTS: The rs7421861 CT genotype was significantly associated with the risk of colorectal cancer compared to the wild-type TT genotype (adjusted OR 1.314, 95% CI 1.012-1.706, P = 0.041). The rs2705535 TT genotype was associated with the risk of rectal cancer [OR 1.819 (1.093-3.027), P = 0.021]. There was statistical interaction between the PD-1/rs2227982 (CT + TT) genotypes and high seafood intake (>once/week), as well as the CTLA-4/rs231777 variant and high pungent food intake (>3 times/week). The AG + AA genotypes of CTLA-4/rs3087243 statistically and antagonistically interacted with soybeans, pork and alcohol intake and were associated with CRC risk. Analogously, BTLA/rs1844089 interacted with pork intake, PD-1/rs7421861 with beef and lamb consumption and PD-1/rs6710479 with barbecue consumption. Haplotype G-C-G-A-T-T-A was significantly associated with CRC risk (OR 1.221 P = 0.034). CONCLUSIONS: These data indicate potential associations between BTLA and PD-1 polymorphisms and CRC susceptibility. Additionally, the three co-inhibitory molecule gene SNPs have environmental interactions associated with CRC risk.

Intronic and promoter polymorphisms of hMLH1/hMSH2 and colorectal cancer risk in Heilongjiang Province of China.

PURPOSE: Given that mismatch repair (MMR) system plays an important role in recognizing and removing insertion/deletion mutations which occur during DNA replication, common variants associated with impaired MMR system may thus increase risk of colorectal cancer (CRC). Therefore, we aimed to demonstrate the associations between common variants in two MMR genes (hMLH1 and hMSH2) and CRC risk. METHODS: We genotyped 10 intronic/promoter single-nucleotide polymorphisms (SNPs) of hMLH1 and hMSH2 in 451 CRC patients and 630 controls. Associations between genotypes and CRC risk were estimated using odds ratios and 95 % confidence intervals. Gene-gene interactions, as well as gene-environment interactions on CRC risk were also investigated. RESULTS: We found that IVS15-214T>C and IVS11 + 107A>G of hMSH2 were significantly associated with CRC risk. In dominant model, variant carriers of the two SNPs could decrease risk of CRC by 31 % (ORadj = 0.69, 95 % CI 0.53-0.91, p < 0.01) and 33 % (ORadj = 0.67, 95 % CI 0.47-0.95, p = 0.02), respectively. In addition, IVS7-212T>A, IVS11+183A>G and IVS8+719T>C of hMSH2 were associated with the susceptibility to colon cancer rather than rectal cancer. ATTTGGGT and TCTTAGAC haplotypes were associated with 44 and 45 % decreased risk of CRC, respectively, while ATTTGAGT and TTTCAGAC haplotypes were associated with 1.37-fold and 2.49-fold increased risk of CRC, respectively. There was a significant three-way gene-gene interaction among hMSH2 IVS11+107A>G, IVS11+183A>G and IVS8+719T>C (p < 0.01). Significant gene-environment interactions were observed between hMSH2 IVS15-214T>C and IVS11+107A>G and cereals consumption (both with p < 0.01). CONCLUSIONS: Our findings suggested that intronic SNPs, gene-gene and gene-environment interactions in hMSH2 might be associated with susceptibility to CRC.

Variations in the PBEF1 gene are associated with body mass index: A population-based study in northern China.

OBJECTIVE: PBEF1 and its polymorphisms may be important in the physiopathology of obesity. We hypothesized that polymorphisms in PBEF1 gene may modify body mass index (BMI). METHODS: Thus, we systematically screened 4 tagging polymorphisms (rs4730153, rs2058540, rs3801267 and rs16872158) in PBEF1 gene and evaluated the association between the genetic variants and BMI in a population-based study including 442 subjects in northern China. RESULTS: We found that the SNP rs3801267 was significantly associated with decreased BMI (P = 0.026 in additive model), while the other 2 SNPs (rs4730153 and rs16872158) showed a borderline significant association with decreased BMI (P = 0.068 and 0.060 in additive models). Combined analysis of these 3 SNPs showed a significant allele-dosage association between the number of variant alleles and decreased BMI (P trend  = 0.007). CONCLUSIONS: These findings indicate that genetic variants in PBEF1 gene may modify individual BMI in the Chinese population.

Decreased proliferation ability and differentiation potential of mesenchymal stem cells of osteoporosis rat.

OBJECTIVE: To explore decreased proliferation ability and differentiation potential of mesenchymal stem cells (MSCs) of osteoporosis rat. METHODS: MSCs were obtained from osteoporosis rat, and proliferation potency and impaired osteogenic differentiation potential were determined. RESULTS: The result showed a significant downregulation of MSCs pluripotency related gene (Oct 4) and osteogenic genes (BSP, OCN) expression in OVX MSCs compared with Sham MSCs (P<0.05). CONCLUSIONS: These data suggest that MSCs are aging in osteoporosis body, and autologous OVX MSCs transplantation is not appropriate to treat osteoporosis if necessary. There will be a possibility in establishing a new clinical application of MSCs autologous transplantation to treat osteoporosis, if OVX MSCs have stronger proliferation and differentiation.

Association of ADAMTS5 gene polymorphisms with osteoarthritis in Chinese Han population: a community-based case-control study.

Aggrecanase-2 (ADAMTS5) is reported to play essential roles in the pathophysiology of osteoarthritis (OA). To explore the relationship between ADAMTS5 gene polymorphisms and primary OA, we conducted a community-based case-control study. A total of 732 community residents aged 40-84 years participated in the community-based study in Northeast China. After taking physical examination and radiographic examination, 420 persons of the residents were diagnosed OA (216 women and 204 men). The other 312 individuals without any symptoms of osteoarthritis or signs in the radiographs (156 women and 156 men) were considered as healthy controls. After obtaining the DNA of patients and control group, genotypes of the ADAMTS5 gene polymorphisms were determined by polymerase chain reaction (PCR) followed by restriction enzyme digestion (HAEIII for P692L in exon 7 and BSRBI for R614H in exon 5). The numbers of patients with different OA subtypes were also calculated. The genotype and allele frequency of for the exon 5C/T BSRBI polymorphism was significantly different between OA patients and control individuals (P = 0.001, OR = 0.701, 95% CI = 0.569-0.863). This difference was more obvious in cervical OA patients (P = 0.001, OR = 0.664, 95% CI = 0.521-0.847). The mutation type of exon 5C/T BSRBI polymorphism would be a protective factor for OA especially for cervical OA. Our results suggest that the ADAMTS5 gene polymorphisms may contribute to the susceptibility of osteoarthritis in the Chinese Han population.

MATN3 gene polymorphism is associated with osteoarthritis in Chinese Han population: a community-based case-control study.

BACKGROUND: The matrilin, especially matrilin-3 (MATN3), are reported to play important roles in the pathophysiology of osteoarthritis (OA). To explore the relationship between MATN3 SNP6 (rs8176070) and primary OA, we conducted a community-based case-control study. METHODS: A total of 732 community residents aged 40-84 years participated in the community-based study in Northeast China. After taking physical and radiographic examinations, 420 of the residents were diagnosed OA (216 women and 204 men). The other 312 individuals without any symptoms of osteoarthritis or signs in the radiographs (156 women and 156 men) were considered as healthy controls. After obtaining the DNA of case and control groups, genotypes of the MATN3 SNP6 were determined by polymerase chain reaction followed by restriction enzyme digestion. The numbers of patients with different OA subtypes were also calculated. RESULTS: The distribution of genotypes and alleles of the MATN3 SNP6 between OA patients and controls was different significantly. The BB carrier tends to be associated with the increased osteoarthritis (P = 0.025, OR = 1.724, 95% CI = 1.071-2.77), especially the knee osteoarthritis (P = 0.021, OR = 2.402, 95% CI = 1.141-5.060) and lumber osteoarthritis (P = 0.020, OR = 1.880, 95% CI = 1.103-3.204). Bb carrier increased hand osteoarthritis risk (P = 0.002, OR = 5.380, 95% CI = 1.828-15.835). The B allele might have an effect on the increased knee osteoarthritis (P = 0.000, OR = 3.143, 95% CI = 2.283-4.328). CONCLUSION: These findings suggest that the MATN3 gene polymorphism might be associated with osteoarthritis in the Chinese Han population.

Prevalence and associated factors of knee osteoarthritis in a community-based population in Heilongjiang, Northeast China.

Few data exist concerning the prevalence of knee OA and associated factors in Northeast China. This study was undertaken to estimate the prevalence of radiographic and symptomatic knee OA among community residents and to elucidate relevant risk factors. Unmatched case-control study was adopted to study risk factors of knee OA. Radiographic OA was evaluated according to the Kellgren and Lawrence grading scheme. Statistical analyses included tests and logistic model regressions. A total of 1,196 people aged 40-84 years participated in the community-based health survey in Northeast China in 2005. Survey participants completed an interviewer-based questionnaire. The standardized prevalence of symptomatic knee OA was 16.05% and it was significantly higher in women than in men (19.87% vs. 11.91%, = 13.76, P < 0.001). There was also an increased tendency with age in both sex (men: x (2) = 29.67, P (trend) < 0.001; women: x (2) = 40.26, P (trend) < 0.001). The prevalence of symptomatic knee OA was significantly higher than that in Beijing and Shantou, while lower than that in Wuchuan county of inner Mongolia with nonsignificant difference. Logistic regressions revealed that age, sex, BMI, and work status might be risk factors for knee OA in urban residents, whereas age, BMI, and smoking habits might be risk factors in rural dwellers. Symptomatic knee OA is extremely common with preponderance for elderly women and constitutes a major public health problem. The findings will be useful to guide the distribution of future health care resources and preventive strategies.

Body mass index and susceptibility to knee osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: Excess bodyweight, expressed as increased body mass index, is associated with osteoarthritis risk, especially in weight bearing joints. However, the strength of the association was inconsistent. The study was conducted to quantitatively assess the association between body mass index and the risk of knee osteoarthritis and investigate the difference of the strength stratified by sex, study type and osteoarthritis definition. METHODS: We used published guidelines of the Meta-analysis of Observational Studies in Epidemiology Group (MOOSE) to perform the meta-analysis. The search strategy employed included computerized bibliographic searches of MEDLINE, PubMed, EMBASE, The Cochran Library and references of published manuscripts. Study-specific incremental estimates were standardized to determine the risk of knee osteoarthritis associated with a 5 kg/m(2) increase in BMI. RESULTS: Twenty-one studies were included in the study. The results showed that body mass index was significantly positive associated with osteoarthritis risk in knee site. A 5-unit increase in body mass index was associated with an 35% increased risk of knee osteoarthritis (RR: 1.35; 95%CI: 1.21, 1.51). Magnitude of the association was significantly stronger in women than that in men with significant difference (men, RR: 1.22; 95%CI: 1.19, 1.25; women, RR: 1.38; 95%CI: 1.23, 1.54; p=0.04). The summary effect size was 1.25(95%CI: 1.18, 1.32) in case-control studies and 1.37 (95%CI: 1.19, 1.56) in cohort studies (p=0.28). Body mass index was positively associated with knee osteoarthritis defined by radiography and/or clinical symptom (RR: 1.25, 95%CI: 1.17, 1.35) and clinical surgery (RR: 1.54, 95%CI: 1.29, 1.83). The latter tended to be stronger than the former (p<0.01). CONCLUSION: Increased body mass index contribute to a substantially increased risk of knee OA. The magnitude of the association varies by sex and OA definition.

The relationship between body mass index and hip osteoarthritis: a systematic review and meta-analysis.

OBJECTIVE: Body mass index, a measure of relative weight, is increasingly recognized as an important risk factor for osteoarthritis, especially in weight bearing joints. The objective was to assess the association between body mass index and hip osteoarthritis susceptibility and investigate the difference between sex, study type and osteoarthritis definition. METHODS: We did electronic searches of Medline, Embase and Cochrane library from the commencement to December 2009. A meta-analysis and meta-regression was executed to quantitatively assess the strength of associations between body mass index and hip osteoarthritis risk. Study-specific incremental estimates were standardized to determine the risk associated with a 5 kg/m(2) increase in body mass index. RESULTS: Fourteen epidemiological studies were included. Our study showed that body mass index was significantly positive associated with hip osteoarthritis risk. A 5-unit increase in body mass index was related to an increased risk of hip osteoarthritis (RR: 1.11; 95%CI: 1.07, 1.16). The magnitudes of associations were similar in women as compared with men (women, RR: 1.10; 95%CI: 1.05, 1.15; men, RR: 1.08; 95%CI: 1.04, 1.12; p > 0.05). The summary estimates were 1.12 (95%CI: 1.02, 1.24) in case-control studies and 1.11 (95%CI: 1.06, 1.16) in cohort studies (p > 0.05). Body mass index was positively associated with hip osteoarthritis defined by radiography and/or clinical symptom (RR: 1.04; 95%CI: 1.00, 1.07) and clinical surgery (RR: 1.16; 95%CI: 1.11, 1.22) with no significant difference (p > 0.05). CONCLUSION: Increased body mass index contributes to a positive effect on susceptibility to hip osteoarthritis. Associations between body mass index and hip osteoarthritis risk do not vary by sex, study design or osteoarthritis definition.

[A comparative study on the prevalence of osteoarthritis in middle and old-aged people from the urban and the rural area in Heilongjiang province].

OBJECTIVE: To investigate the prevalence of osteoarthritis in inhabitants aged 40 years old and above from urban and rural areas in Heilongjiang province. METHODS: Through multistage stratified cluster random sampling methods, residents aged 40 years and above were selected. All subjects were given a standardized questionnaire and were conducted a radiographic examination on hands, knees, neck spine and lumbar spine after informed consent. All statistics were performed by SPSS13.0. RESULTS: A total of 1196 residents were surveyed, which including 573 males and 623 female subjects. The prevalence of osteoarthritis in cervical spine, lumbar spine, knee and hand for men were 26.00%, 31.20%, 11.87%, 15.53%, respectively and that were 34.80%, 30.20%, 20.06%, 27.93% for women respectively. The prevalence of osteoarthritis increased with aging both in men and women. Prevalence in 60 - 70 age group achieved the peak. The prevalence rates became relatively low among those over the 70 years old than expected. The most common sites of osteoarthritis were knees and hands (16.10%), followed by cervical and lumbar spine (12.40%). CONCLUSION: The prevalence of osteoarthritis was generally high in middle and old-aged people in Heilongjiang province.

Novel gene P28GANK confers multidrug resistance by modulating the expression of MDR-1, Bcl-2 and Bax in osteosarcoma cells.

As previously reported, a novel gene P28GANK conferred a multidrug resistant phenotype in gastric cancer cells. The aim of this study was to explore the role of P28GANK in the development of multidrug resistance (MDR) in osteosarcoma cells. P28GANK gene was found to be overexpressed at the mRNA level and the protein level in a cisplatin induced MDR osteosarcoma cell line Saos-2/CDDP compared to its parent cell line Saos-2. Here, we transfected the osteosarcoma cell line Saos-2 with eukaryotic expression vector of P28GANK. In vitro drug sensitivity assay suggested that Saos-2-P28GANK cells conferred resistance to both P-glycoprotein (P-gp)-related and P-gp-nonrelated drugs. Blocking P28GANK expression in MDR osteosarcoma cells Saos-2/CDDP by P28GANK-specific small interfering RNA (siRNA) increased the cell sensitivity to various chemotherapeutic drugs. Flow cytometry examination suggested that P28GANK gene expression could suppress Adriamycin-induced apoptosis accompanied by decreased accumulation and increased release of Adriamycin. Semiquantitative RT-PCR, Western blot and Luciferase reporter assay suggested that P28GANK gene could significantly up-regulate the expression of MDR-1 and Bcl-2, transcription of the MDR-1 gene and down-regulate the expression of Bax. In addition, inhibition of P28GANK expression by RNA interference or P-gp inhibition could partially reverse P28GANK-mediated MDR. Taken together, our findings suggest that down-regulation of P28GANK gene expression could sensitize osteosarcoma cells to chemotherapeutic drugs by down-regulation of the MDR-1 and Bcl-2 and up-regulation of Bax gene expression, without altering the glutathione S-transferase activity, or intracellular glutathione content in osteosarcoma cells. Further study on biological function of P28GANK may be helpful for understanding MDR mechanism of osteosarcoma and developing a strategy for osteosarcoma treatment.