Correlated non-nuclear COX2 and low HER2 expression confers a good prognosis in colorectal cancer.

BACKGROUND/AIMS: COX2 and HER2 are shown to be critical in the regulation of cancer progression. However, the prognostic value of nuclear COX2 in colorectal cancer (CRC) and its relationship with HER2 still remains unknown. In this study, the expression and biological significance of COX2 and HER2 were evaluated in CRC at mRNA and protein levels. MATERIALS AND METHODS: RNA-Seq data of CRC were downloaded from TCGA, and 229 CRC and 50 non-cancerous subjects were enrolled in this study. Bioinformatics and immunohistochemistry analysis was performed based on the obtained data. Survival analysis was conducted to identify factors associated with overall survival of CRC patients. RESULTS: We showed that mRNA and protein levels of COX2 and HER2 were upregulated in CRC compared with the adjacent tissues. COX2 protein levels and nuclear COX2 expression were correlated with a poor prognosis of CRC patients. In addition, we also revealed that nuclear COX2 expression was positively associated with HER2 expression. Non-nuclear COX2 combined with low HER2 expression, was negatively correlated with Duke's stage and lymph node metastasis, predicting the best outcomes for CRC patients. In addition, our data indicated that non-nuclear COX2 combined with low HER2 expression is an independent prognostic factor for CRC after surgical resection. CONCLUSION: The study suggests that nuclear COX2 in combination with HER2 can serve as potential biomarkers for the clinical diagnosis and prognosis of CRC, and targeted inhibition of COX2 and HER2 might be an alternative strategy for the management of CRC.

[Gene Analysis of Thalassemia in Han and Dai Ethnic Childbearing-aged Population of Chinese Yunnan Province].

OBJECTIVE: To investigate the common mutation spectrum of α- and ß-thalassemia in Yunnan childbearing-aged population. METHODS: The common mutation types of α- or ß-globin genes were detected by multiple Gap-PCR and the PCR-reversed dot blotting, and the unknown mutation types were determined by DNA sequencing in DNA samples of hypochromic microcytic anemia patients and carriers who were confirmed to be positive by serologic screaning, then the mutation types of globin in Yunnan population were analyzed statistically. RESULTS: A total of 40 kinds of mutation types were detected in 685 detected persons, among them the 3 commonest mutation types of α-globin genes were --(SEA)/αα (49.09%), -α(3.7)/αα (36.67%) and α(CS)α/αα (8.79%), the 3 commonest genetypes of ß-globin gene were CD26(GAG>AAG)/N (43.78%), CD41-42(-CTTT)/N (20.1%) and CD17(AAG>TAG)/N (18.9%). There were 348 Han and 212 Dai ethnic persons in 685 cases, but their mutation of globin genes were different between these 2 ethnic groups. The results also showed that the gene mutation types were mostly concentrated in Dai ethnic individuals, since 28 of 38 detected α-ß-thalassemia cases were Dai ethnic individuals. CONCLUSION: The mutation spectrums of α- and ß-globin genes in Yunnan childbearing-aged population are diverse and different from that in other areas of China.

[Gene Mutation Spectrum of ß-Thalassemia in Dai Ethinic Population of Two Border Region in Chinese Yunnan Province].

OBJECTIVE: To investigate the gene mutation spectrum of ß-thalassemia in Dai ethnic population of 2 border region in Chinese Yunnan Province. METHODS: The patients with ß-thalassemia in Dai ethnic population of Dehong and Xishuangbanna autonamic prefecture were screened by using blood routine detection and capillary electrophoresis. The ß-globin gene mutation in patients with ß-thalassemia were detected by using PCR reverse dot-blot hybridization (PCR-RDB), the constitutive rate of gene mutation in patients with ß-thalassemia of Dai ethnic population in two border regions was analyzed and compared. RESULTS: A total of 186 patients with gene mutation of ß-thalassemia were confirmed. Among them, 10 gene mutation were found, and the 5 main gene mutations were CD26 (62.56%), CD41-42 (18.97%), CD17 (14.36%), CD71-72 (2.05%) and IVS-II-654 (1.54%). Among Dai ethinic population in Dehong region, 4 gene mutations were found including CD26 (80.31%), CD17 (11.02%), CD41-42 (6.30%) and CD71-72 (2.36%). Among Dai ethinic population in Xishuangbanna region, 6 gene mutations were found, out of them the more common gene mutations were CD41-42 (42.64%), CD26 (29.41%) and CD17 (20.59%). CONCLUSION: The gene mutations of ß-thalassemia in Dai ethinic population of Yunnan province has been confirmed to be more genetic heterogenicity, the spectrums of ß-thalassemia mutations in Dai ethinic population of different regions were significant different.

Genetic heterogeneity of the ß-globin gene in various geographic populations of Yunnan in southwestern China.

OBJECTIVES: The aim of this study was to investigate the geographic distribution of ß-globin gene mutations in different ethnic groups in Yunnan province. METHODS: From 2004 to 2014, 1,441 subjects with hemoglobin disorders, identified by PCR-reverse dot blot and DNA sequencing, were studied according to ethnicity and geographic origin. Haplotypes were examined among 41 unrelated thalassemia chromosomes. RESULTS: Eighteen ß-thalassemia mutations and seven hemoglobin variants were identified for 1,616 alleles in 22 different ethnic groups from all 16 prefecture-level divisions of Yunnan. The prevalence of ß-thalassemia was heterogeneous and regionally specific. CD 41-42 (-TCTT) was the most prevalent mutation in the populations of northeastern Yunnan. CD 17 (A>T) was the most common mutation in the populations of southeastern Yunnan, especially for the Zhuang minority, whereas Hb E (CD 26, G>A) was the most prevalent mutation in populations of southwestern Yunnan, especially for the Dai minority. Among the seven types of haplotypes identified, CD 17 (A>T) was mainly linked to haplotype VII (+ - - - - - +) and IVS-II-654 (C>T) was only linked to haplotype I (+ - - - - + +). CONCLUSION: Our data underline the heterogeneity of ß-globin gene mutations in Yunnan. This distribution of ß-globin mutations in the geographic regions and ethnic populations provided a detailed ethnic basis and evolutionary view of humans in southern China, which will be beneficial for genetic counseling and prevention strategies.

The spectrum of α- and ß-thalassemia mutations in Yunnan Province of Southwestern China.

The aim of this study was to investigate the spectrum of thalassemia mutations in Yunnan Province, Southwestern China. We detected 450 thalassemia patients and carriers by multiplex gap polymerase chain reaction (gap-PCR), PCR reverse dot-blot hybridization and direct sequencing methods in 535 suspected patients. Four types of α-thalassemia (α-thal) mutations, - -(SEA) (59.2%), -α(3.7) (rightward) (19.0%), Hb Constant Spring [Hb CS, α142, Term→Gln, TAA>CAA (α2), α(CS)α] (15.5%), and -α(4.2) (leftward) (6.34%) were detected. Six types of ß-thal mutations, the most prevalent being Hb E [ß26(B8)Glu→Lys, GAG>AAG or codon 26 (G>A)] (30.5%), followed by codon 17 (A>T) (20.8%), codons 41/42 (-TCTT) (17.5%), IVS-II-654 (C>T) (17.2%), -28 (A>G) (6.95%), and codons 71/72 (+A) (2.42%) were also detected. Other rare mutations were codons 27/28 (+C), IVS-I-1 (G>T), Hb New York [ß113(G15)Val→Glu, GTG>GAG], Hb D-Los Angeles [ß121(GH4)Glu→Gln, GAA>CAA], codon 5 (-CT), Hb G-Taipei [ß22(B4)Glu→Glu (GAA>GGA)], Hb J-Lome [ß59(E3)Lys→Asn (AAG>AAC)], Hb J-Bangkok [ß56(D7)Gly→Asp (GGC>GAC)], IVS-I-2 (T>C), and -31 (A>C). In this study, we provide a complete mutation spectrum of α- and ß-thal mutations and a valuable strategy for accurate molecular diagnostic testing in Yunnan Province, People's Republic of China (PRC).

[A study on gene mutation spectrums of α- and ß-thalassemias in populations of Yunnan Province and the prenatal gene diagnosis].

OBJECTIVE: To investigate mutation spectrums of α- and ß-haemoglobin genes in thalassemia patients and carriers in Yunnan province, and to establish procedures on prenatal gene diagnosis. METHODS: Totally 10 033 counseling couples and pregnant women, and 22 cases of children with moderate or severe thalassemia were recruited from 5 parts of Yunnan Province, middle, western, eastern, southern and northern areas, during July 2009 to July 2011. Medical records, including results of haemoglobin electrophoresis, blood routine examination, and gene diagnosis of subjects were collected and saved in an database in Excel software by the Key Laboratory for Birth Defects and Genetic Diseases. Using multiple gap-PCR and PCR-reversed dot blotting kits, DNA samples collected from 1077 cases of haematological positive thalassemia patients and carriers were tested to determine common mutations of the α- or ß-haemoglobin genes. The codon regions of haemoglobin genes were sequenced by the Sanger sequencing in cases that the mutation tests were negative. Mutation spectrums of α- and ß-haemoglobin genes were concluded. Prenatal gene diagnosis was offered to fetuses who had risk of thalassemia major. RESULTS: (1) In 1077 cases of haemological screen positive subjects, deletions and mutations of α-haemoglobin gene were tested in 119 subjects among 347 cases suspected as α-thalassemia patients and carriers. Five kinds of deletions and mutations on α-haemoglobin gene were found. In 104 subjects, four kinds of common deletions and mutations onα-haemoglobin gene were determined: --(SEA), -α(3.7), α(CS)α, -α(4.2). Other 14 subjects were double heterozygotes with haemoglobin H disease and severe α-thalassemia phenotypes. A rare mutation of insertion and deletion in α2 haemoglobin gene intron, α(301-24_301-23 indel), was found in one carrier subject. (2) In 1077 cases of haemological screen positive subjects, deletions and mutations of ß-haemoglobin gene were tested in 297 subjects among 730 cases suspected as ß-thalassemia patients and carriers. Sixteen kinds of ß-haemoglobin gene mutations were found, including 7 cases of rare abnormal haemoglobinopathy patients with ß-haemoglobin gene mutations. In one case with ß(+) phenotype patient, the Codon 5(-CT) mutation at ß-haemoglobin gene was found (firstly reported in China). (3) Three fetuses with high risks of α-thalassemia were accepted for prenatal diagnosis. One case of Hb Bart's hydrops syndrome fetus with the genotype --(SEA)/--(SEA), and one case of mild α-thalassemia fetus with the genotype α(CS)α/αα were found. Another one fetus was found with normal α-haemoglobin. In 6 fetuses accepted for prenatal diagnosis due to high risks of ß-thalassemia, one case of ß-thalassemia major with the genotype CD(17)(A→T)/-28(A→G) was found, 3 fetuses were heterozygote carriers, and 2 fetuses had normal genotypes without mutations found in their parents. Medical terminations for 2 fetuses with severe thalassemia were made according to the choice of pregnant women. Other 7 pregnancies continued to term. Anemia or growth retardation was not found in the 7 infants when following up after given-birth 6 to 12 months. CONCLUSIONS: The mutation spectrums of α- and ß-haemoglobin genes of thalassemia patients and carriers in Yunnan province are special, in which ß-haemoglobin gene exits more polymorphism in the mutation spectrum. Carrier screening in pregnant women, and offering prenatal gene diagnosis to the high risk pregnancies should be an efficient strategy to prevent thalassemia major.