Biological basis of extensive pleiotropy between blood traits and cancer risk.

BACKGROUND: The immune system has a central role in preventing carcinogenesis. Alteration of systemic immune cell levels may increase cancer risk. However, the extent to which common genetic variation influences blood traits and cancer risk remains largely undetermined. Here, we identify pleiotropic variants and predict their underlying molecular and cellular alterations. METHODS: Multivariate Cox regression was used to evaluate associations between blood traits and cancer diagnosis in cases in the UK Biobank. Shared genetic variants were identified from the summary statistics of the genome-wide association studies of 27 blood traits and 27 cancer types and subtypes, applying the conditional/conjunctional false-discovery rate approach. Analysis of genomic positions, expression quantitative trait loci, enhancers, regulatory marks, functionally defined gene sets, and bulk- and single-cell expression profiles predicted the biological impact of pleiotropic variants. Plasma small RNAs were sequenced to assess association with cancer diagnosis. RESULTS: The study identified 4093 common genetic variants, involving 1248 gene loci, that contributed to blood-cancer pleiotropism. Genomic hotspots of pleiotropism include chromosomal regions 5p15-TERT and 6p21-HLA. Genes whose products are involved in regulating telomere length are found to be enriched in pleiotropic variants. Pleiotropic gene candidates are frequently linked to transcriptional programs that regulate hematopoiesis and define progenitor cell states of immune system development. Perturbation of the myeloid lineage is indicated by pleiotropic associations with defined master regulators and cell alterations. Eosinophil count is inversely associated with cancer risk. A high frequency of pleiotropic associations is also centered on the regulation of small noncoding Y-RNAs. Predicted pleiotropic Y-RNAs show specific regulatory marks and are overabundant in the normal tissue and blood of cancer patients. Analysis of plasma small RNAs in women who developed breast cancer indicates there is an overabundance of Y-RNA preceding neoplasm diagnosis. CONCLUSIONS: This study reveals extensive pleiotropism between blood traits and cancer risk. Pleiotropism is linked to factors and processes involved in hematopoietic development and immune system function, including components of the major histocompatibility complexes, and regulators of telomere length and myeloid lineage. Deregulation of Y-RNAs is also associated with pleiotropism. Overexpression of these elements might indicate increased cancer risk.

An unusual presentation of cryptorchidism: A case report of Spigelian-cryptorchidism syndrome.

INTRODUCTION: Spigelian hernia is an uncommon hernia presenting as a protrusion of abdominal contents through the spigelian fascia, lateral to the rectus abdominis. In some rare cases, Spigelian hernia can occur alongside cryptorchidism, which forms a recognized syndrome found in male infants with Spigelian hernia. This is a relatively unreported syndrome with very limited literature available regarding it, none of which is reported in Pakistan in adults. PRESENTATION OF CASE: We report a case of a 65-year-old male with right sided obstructed spigelian hernia along with the rare finding of testis in the hernial sac. The patient was successfully managed by transperitoneal primary repair (herniotomy) with orchiectomy. The patient recovered uneventfully and was discharged 5 days after the surgery. DISCUSSION: The exact pathophysiology of this syndrome remains unclear. Three theories have been proposed to explain this syndrome, including the primary defect being Spigelian hernia leading to undescended testes (Al-Salem), testicular maldescent preceding the formation of the hernia (Raveenthiran), or the absence of the inguinal canal leading to the development of a rescue canal due to the undescended testes (Rushfeldt et al.). In this case, the absence of gubernaculum was confirmed suggesting the findings to be consistent with Rushfeldt's theory. The surgical team proceeded with hernial repair and orchiectomy. CONCLUSION: In conclusion, Spigelian-Cryptorchidism syndrome is a rare syndrome in adult male, with an unclear pathophysiology. Management of this condition involves repair of the hernia along with either orchiopexy or orchiectomy, depending upon the risk factors involved.

Patterns of Genetic Diversity among Alphasatellites Infecting Gossypium Species.

Alphasatellites are small single-stranded circular DNA molecules associated with geminiviruses and nanoviruses. In this study, a meta-analysis of known alphasatellites isolated from the genus Gossypium (cotton) over the last two decades was performed. The phylogenetic and pairwise sequence identity analysis suggested that cotton-infecting begomoviruses were associated with at least 12 different alphasatellites globally. Three out of twelve alphasatellite were associated with cotton leaf curl geminiviruses but were not isolated from cotton plants. The cotton leaf curl Multan alphasatellite, which was initially isolated from cotton, has now been reported in several plant species, including monocot plants such as sugarcane. Our recombination analysis suggested that four alphasatellites, namely cotton leaf curl Lucknow alphasatellites, cotton leaf curl Multan alphasatellites, Ageratum yellow vein Indian alphasatellites and Ageratum enation alphasatellites, evolved through recombination. Additionally, high genetic variability was detected among the cotton-infecting alphasatellites at the genome level. The nucleotide substitution rate for the replication protein of alphasatellites (alpha-Rep) was estimated to be relatively high (~1.56 × 10-3). However, unlike other begomoviruses and satellites, the first codon position of alpha-Rep rapidly changed compared to the second and third codon positions. This study highlights the biodiversity and recombination of alphasatellites associated with the leaf curl diseases of cotton crops.

miR-140-3p is a potential differential biomarker in benign phyllodes tumors and fibroadenoma of the breast.

BACKGROUND: Benign phyllodes tumor (BPT) and fibroadenoma (FA) have some difficulties in differential diagnosis. BPT is often misdiagnosed as FA during the first operation and is not diagnosed until postoperative recurrence and reoperation. The intent of this research was to find and validate microRNAs (miRNAs) with significant differential expression between BPT and FA as novel potential differential biomarkers. METHODS: Tissue specimens from three BPT patients and three FA patients were selected to detect the expression of miRNAs by miRNA-Seq technique. Primary cells were extracted and cultured from fresh BPT and FA tissues by tissue-block culture. The expression of differentially expressed miRNA (DEmiRNA) was further verified by quantitative real-time polymerase chain reaction (qRT-PCR) in twelve BPT and eleven FA patient specimens as well as primary cells. Data with a P value < 0.05 were considered statistically significant. RESULTS: The miRNA-Seq results showed totally six DEmiRNA were identified, consisting of two downregulated genes and four upregulated genes in BPT. Further validation by qRT-PCR manifest that miR-140-3p was downregulated by approximately 70% in BPT. CONCLUSION: miR-140-3p could become potential differential biomarker for BPT and FA.

Patients with true mixed growth hormone and prolactin-secreting pituitary adenoma: a case series of 12 patients.

Objective: Mixed growth hormone (GH) and prolactin (PRL) secreting adenomas are the most common type of plurihormonal pituitary adenomas. We assessed the clinical presentations and impacts of transsphenoidal surgery (TS) on patients with mixed GH and PRL adenomas including surgical outcomes, complications, and prognosis.Method and patients: Twelve patients (7 males, 5 females) were operated in the neurosurgery department of Qilu hospital affiliated to Shandong University, Shandong, China. We analyzed hormone levels of preoperation, postoperation (within 24 h) and at 12-month follow-up and correlated levels with tumor volumes.Results: The remission rate was 66.7% (8/12), the recurrence rate was 16.7% (2/12), the cause-specific mortality was 0 and the overall mortality rate was 16.7% (2/12) due to stroke and myocardial infarction respectively. A significant drop was seen in GH, PRL, and Insulin-like-growth-factor-1 (IGF-1) levels between preoperation and postoperation with mean values from 52.6 to 9.9 ng/ml (p = 0.0015), from 321.6 to 190.9 ng/ml (p = 0.0026) and from 815.7 to 230.6 ng/ml (p = 0.0004), respectively. This drop was more significant between preoperation and follow-up with mean values from 52.6 to 3.0 ng/ml (p = 0.002), from 321.6 to 61.6 ng/ml (p < 0.0001), and from 815.7 to 195.0 ng/ml (p = 0.0001), respectively. However, there was no significant correlation between tumor volume and all of the hormone levels.Conclusions: Most mixed GH and PRL adenomas are aggressive with a high risk of recurrence and mortality.