Exploring the Oncogenic Potential of TIMM8A: A Crucial Factor in Breast Cancer Tumorigenesis.

BACKGROUND: Female breast cancer has become the world's most common malignant tumor, displacing lung malignancy, and the incidence of malignant tumors has increased continuously in recent decades. However, the underlying molecular mechanisms of breast tumorigenesis have not been fully elucidated. By consulting the literature, we discovered that the TIMM8A gene could affect oxidative stress and apoptosis in patients with Mohr-Tranebjærg syndrome. However, the biological function of TIMM8A has yet to be explored. MATERIALS AND METHODS: We investigated the expression level of TIMM8A via bioinformatic analysis and performed immunohistochemistry, diagnostic value, immune infiltration, functional enrichment, and survival analyses. Nonetheless, in vitro, additional experiments were performed. We explored whether TIMM8A expression was greater in breast tumors than in nearby normal tissues through qRT‒PCR. The expression of TIMM8A was knocked down by siRNA. Then, we conducted proliferation tests (CCK-8 experiment and colony formation) and Transwell assays (migration and invasion assays) to determine the specific biological functions of TIMM8A in the MDA-MB-231 and BT-549 cell lines. RESULTS: Tumor samples exhibited higher TIMM8A expression and exon expression, whereas normal tissues had higher TIMM8A methylation. The expression level of TIMM8A was linked to immune infiltration and survival, making it a valuable prognostic indicator and effective diagnostic tool. Functional enrichment analysis of TIMM8A indicated potential pathways through which it may play a role. In vitro experiments demonstrated that suppressing TIMM8A significantly inhibited the viability, colony formation, migration, and invasion of breast carcinoma cell lines. CONCLUSION: This study revealed that TIMM8A is an oncogene and is critical for the tumorigenesis of breast carcinoma.

GNPNAT1 is a Biomarker That Predicts a Poor Prognosis of Breast Cancer.

Background: Breast cancer (BC) is increasingly becoming the primary reason for death in women, which sounded the alarm. Thus, finding a novel management target for BC is imminent. Materials and Methods: The data on gene expression and clinicopathological characteristics were downloaded from The Cancer Genome Atlas (TCGA). The expression of GNPNAT1 in 40 paired breast cancer and adjacent tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Univariate and Multivariate logistic regression methodology was applied to analyze the prognostic factors for lymph node metastasis (LNM). Based on the status of breast cancer-relative receptors, patients were distributed into six groups, and then the Kaplan-Meier survival analysis with a Log rank test was applied to investigate the involvement among the expression of GNPNAT1 and overall survival (OS). Results: We found higher expression of GNPNAT1 was connected with poor survival in breast cancer by COX regulation analysis. GO, KEGG, and GSEA analysis prompted that GNPNAT1 was connected with the defense mechanism of cells, cell proliferation, and division. Immunization infiltration analysis showed that high GNPNAT1 was negatively connected with 16 immunization infiltration cell types and positively connected with four immunization infiltration cell types. Conclusion: As a whole, our results indicated that GNPNAT1 might be a probable biomarker for diagnosis and prognosis in breast cancer.

Serine Protease 27, a Prognostic Biomarker in Pan-cancer and Associated with the Aggressive Progression of Breast Cancer.

BACKGROUND: To create effective medicines, researchers must first identify the common or unique genes that drive oncogenic processes in human cancers. Serine protease 27 (PRSS27) has been recently defined as a possible driver gene in esophageal squamous cell carcinoma. However, no thorough pan-cancer study has been performed to date, including breast cancer. METHODS: Using the TCGA (The Cancer Genome Atlas), the GEO (Gene Expression Omnibus) dataset, and multiple bioinformatic tools, we investigated the function of PRSS27 in 33 tumor types. In addition, prognosis analysis of PRSS27 in breast cancer was carried out, as well as in vitro experiments to verify its role as an oncogene. We first explored the expression of PRSS27 in over 10 tumors and then we looked into PRSS27 genomic mutations. RESULTS: We discovered that PRSS27 has prognostic significance in breast cancer and other cancers' survival, and we developed a breast cancer prognostic prediction model by combining a defined set of clinical factors. Besides, we confirmed PRSS27 as an oncogene in breast cancer using some primary in vitro experiments. CONCLUSION: Our pan-cancer survey has comprehensively reviewed the oncogenic function of PRSS27 in various human malignancies, suggesting that it may be a promising prognostic biomarker and tumor therapeutic target in breast cancer.

Monocyte-to-High-Density Lipoprotein Cholesterol Ratio Together With the Lymphocyte-to-Monocyte Ratio in Predicting the Malignancy of the Thyroid Nodule in Patients Complicated With Type 2 Diabetes.

Background: Thyroid nodules, although mostly benign and symptomless, have a small chance of being cancerous, necessitating accurate diagnosis. This study aims to develop and validate a nomogram for differentiating malignant and non-malignant thyroid nodules in individuals with type 2 diabetes. Methods: The study included 484 patients with both thyroid nodules and type 2 diabetes who underwent thyroid gland lobectomy at Wenzhou Medical University Hospital. Optimal cutoff values for continuous variables were determined using ROC curve analysis. Significant factors identified in univariable analysis were used to construct the nomogram. The monocyte-to-high-density lipoprotein cholesterol ratio (MHR) was visualized through a histogram and scatter diagram. Discriminatory power was assessed using ROC analysis, and calibration curves ensured consistency. Decision curve analysis (DCA) evaluated clinical benefits. Results: The cohort was divided into a training group (70%) and an internal validation group (30%). The scatter diagram revealed a correlation between MHR levels and the proportion of goiter cases, with higher MHR levels associated with increased goiter incidence. The histogram showed higher average MHR levels in goiter patients compared to those with papillary thyroid carcinoma (PTC) in both groups. Multivariate logistic regression identified age, total cholesterol (TC), triglyceride (TG), fasting blood sugar (FSG), fibrinogen, lymphocyte-to-monocyte ratio (LMR), and MHR as independent predictive factors for malignancy in thyroid nodules with type 2 diabetes. The nomogram achieved high discrimination, with C-index values of 0.901 (training data set) and 0.760 (internal validation data set). Calibration curves displayed good agreement, and DCA demonstrated significant net clinical benefits. Conclusions: MHR is associated with sex, serum cholesterol levels, and peripheral blood cell counts, making it a potential novel biomarker for differentiating between PTC and goiter in type 2 diabetes patients.

Budding uninhibited by benzimidazoles 1 might be a poor prognosis biomarker promoting the progression of papillary thyroid cancer.

BACKGROUND: Papillary thyroid carcinoma (PTC) is one of the most widespread malignant tumors of the endocrine system, with a high incidence. Budding uninhibited by benzimidazoles 1 (BUB1), one of the spindle assembly checkpoint (SAC) genes, is a multitask protein kinase required for eukaryotic chromosome segregation. Although BUB1 has been explored in several types of cancer, its biological role and molecular mechanisms in PTC remain unclear. METHODS: In this study, we performed an examination of four public datasets along with local PTC cohorts and discovered that BUB1 was elevated in PTC compared to non-cancer tissues. High BUB1 expression was linked with the status of BRAFV600E , RAS, and TERT after statistical analysis. RESULTS: Clinically, BUB1 is associated with a variety of clinicopathological features in PTC patients. Interestingly, analysis of the TCGA database showed that BUB1 was closely associated with poor prognosis of PTC and significantly correlated with PFS. As determined by regression analysis, BUB1, and T stage were independent predictors of PTC and were related to BRAFV600E and lymph node metastatic status. By RT-qPCR, BUB1 was considerably overexpressed in PTC cell lines in comparison with normal thyroid epithelial cells. CONCLUSION: We confirmed that the knockdown of BUB1 in BCPAP and TPC1 cell lines significantly inhibited cell proliferation, cloning, and migration in vitro experiments. These results imply that BUB1 may be a significant oncogenic gene that is directly associated with the prognosis of PTC and may represent a future target for therapeutic intervention.

A Specificity Protein 1 assists the progression of the papillary thyroid cell line by initiating NECTIN4.

AIMS: Papillary thyroid cancer (PTC) is one of the subtypes of thyroid cancer with increasing incidence worldwide, but the molecular mechanism is still unclear. BACKGROUND: Papillary thyroid cancer (PTC) is one of the subtypes of thyroid cancer with increasing incidence worldwide, but the molecular mechanism is still unclear. Studies have indicated that nectin cell adhesion molecule 4 (NECTIN4) was an oncogene and played an important role in the development and progression of PTC. Meanwhile, specificity protein 1 (SP1) expresses many important oncogenes and tumor suppressor genes. However, the relationship between NECTIN4 and SP1 in regulating PTC growth is unclear. OBJECTIVE: In the present study, reverse transcription PCR was utilized to detect the mRNA expression of NECTIN4 and SP1 in thyroid cancer cell lines and normal thyroid cell lines. Chromatin immunoprecipitation assays and luciferase reporter assays were used to study whether SP1 could bind to the promoter region of NECTIN4 and activate its transcription. The biological functions of SP1 correlated with NECTIN4 were also performed in TPC-1 and KTC1 cell lines. METHOD: The study revealed that the mRNA expression level of SP1 and NECTIN-4 showed a positive correlation and were upregulated in PTC cell lines. Moreover, the results of ChIP and luciferase reporter assays showed that SP1 could bind to the NECTIN4 promoter regions and activate the transcriptional level of NECTIN4. RESULT: The experiments in vitro showed that SP1 could promote cell proliferation, colony formation, migration, and invasion by regulating NECTIN4 in PTC cells. CONCLUSION: In conclusion, our study, for the first time, demonstrated that SP1 could control the transcriptional regulation of NECTIN4 and accelerate the growth of PTC, which may provide a new potential therapeutic target for PTC patients.

The pan-cancer analysis of the oncogenic role of FAM72A as a BRCA prognostic biomarker and immunotherapeutic target.

In this study, we first comprehensively investigated the expression profile, mutation status, and survival analysis of FAM72A as well as the correlation between FAM72A and DNA damage repair, methylation, and cell stemness analysis using bioinformatics techniques. In addition, we also analyzed the relationship between FAM72A and immune cell infiltration and pathway enrichment. The role of FAM72A in breast cancer (BC) was so conspicuous that we analyzed the prognostic significance and clinicopathological parameter's relevance of FAM72A in BC. We also validated biological functions by applying in vitro experiments. FAM72A was highly expressed in 26 types of a total of 31 cancers, while it expressed low levels in only five cancers. FAM72A expression was relative to clinical stages in nine cancers and has a significant difference in disease-free survival among 31 kinds of cancers. In addition, FAM72A has negatively correlated with cancer-associated fibroblast and endothelial cells in BC but positively correlated with follicular helper T cells. Univariate and multivariate cox regression analyses identified T, N, M, age, and FAM72A expression as independent influences on BC prognosis, so we created a nomogram to predict patient survival benefits. In in vitro experiments, we verified that downregulation of FAM72A not only inhibited cell proliferation, colony formation, cell migration, cell invasion, and G2/M cell cycle transition but also promoted apoptosis of breast invasive carcinoma cells. Our study discovered FAM72A as a clinically meaningful biomarker for prognostic predicting and a guiding target for immune treatment in BC.

S100A6 promotes the development of thyroid cancer and inhibits apoptosis of thyroid cancer cells through the PI3K/AKT/mTOR pathway.

High levels of S100A6 have been associated with progression in some types of human cancers. Cancers related to S100A6 have been reported to include lung cancer, cervical cancer, pancreatic cancer, gastric cancer, colon cancer, etc., but its role in the molecular pathogenesis of these cancers is largely unknown. This study investigated the expression and functional roles of S100A6 in human thyroid cancer. The expression level of S100A6 in thyroid cancer cells was determined by bioinformatics and transcriptomic analysis. Furthermore, the potential functions of S100A6 in tumorigenesis were analyzed by cell proliferation, migration, invasion, and Western blot assays in human thyroid cancer cells. Public database queries revealed high S100A6 expression in thyroid cancer. In addition, we also found that high expression of S100A6 was positively correlated with malignant clinicopathological characteristics of thyroid cancer in The Cancer Genome Atlas database. qPCR results confirmed the high expression of S100A6 in thyroid cancer cells. S100A6 silencing inhibited cell proliferation, migration, and invasion. Western blot assays and response experiments showed that S100A6 promotes cell proliferation and tumorigenicity partly through the PI3K/AKT/mTOR signaling pathway. These results suggest that S100A6 affects the progression of thyroid cancer and can be used as a target in the future treatment of thyroid cancer.

PDZK1IP1 gene promotes proliferation, migration, and invasion in papillary thyroid carcinoma.

Thyroid cancer is a common malignant tumor for the adult and the potential molecular mechanism of papillary thyroid cancer cell metastasis is still unclear. We used sequencing techniques to analyze paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissue and identified a gene, PDZK1IP1, that was significantly overexpressed in thyroid cancer. We found It has been detected to play an important role in many malignant tumors. But the role in papillary thyroid cancer was still unknown, we decided to find a new marker and therapeutic target for the disease. The present study shows that PDZK1IP1 may be a potential gene that leads to thyroid cancer. In our study, silencing PDZK1IP1 can inhibit PTC cell proliferation, migration, invasion, apoptosis, and cell cycle arrest. This study surmised that PDZK1IP1 was an oncogene that correlated with tumor development.

Right breast schwannoma in a male: A rare case report.

INTRODUCTION: Schwannoma are benign neoplasms of peripheral nerve sheath. They usually occur in the head, neck and the extremities. Breast is a rare location of Schwannoma. CASE PRESENTATION: Our case describes the occurrence of Schwannoma in the right breast, in a 60-year-old male, who has had a breast lump since the last 6 years. After ultrasonography (showed 3.4 × 2.3 × 2.0 cm heteroechoic mass in the upper outer quadrant of the right breast), and mammography (showed 2.5 × 3.2 cm sized high density mass in upper outer quadrant of right breast), an excisional biopsy was performed, and on histopathologic examination, the diagnosis of breast schwannoma was confirmed. DISCUSSION: Clinical and pathological features resemble that of other benign tumors. On ultrasonography they present a well-defined, solid, hypoechoic mass, with some degree of posterior acoustic enhancement. Diagnosis is usually based on histopathologic examination. Microscopically, it exhibits hypercellular antony A areas along with hypocellular antony B areas. Treatment is usually surgical excision. CONCLUSION: Though Schwannomas in breast are rare, they must be considered as differential diagnoses in patients presenting with breast lumps.

Chilaiditi's syndrome in a patient under long-term antidepressants- A case report.

Introduction: Chilaiditi's sign is a rare radiological sign characterized by interposition of the colon between diaphragm and liver. It is called Chilaiditi's syndrome if the patient presents with associated symptoms. Its diagnosis is incidental and can be confused with other acute conditions. Case presentation: This is a case of 85-year-old gentleman who presented with complaints of epigastric pain and vomiting. The patient had a history of long-term antidepressant medications. X-ray of chest and abdomen revealed presence of bowel loops under the diaphragm. CT scan helped confirm the diagnosis of Chilaiditi's sign. Discussion: Chilaiditi's sign has a low prevalence on chest and abdominal X-rays. Common associated symptoms include abdominal pain, nausea, vomiting and constipation. It can be misdiagnosed as bowel perforation and can lead to unnecessary surgical interventions. Symptomatic patients are managed conservatively. Conclusion: Chilaiditi's syndrome is a rare radiological entity and should be diagnosed carefully to avoid unwanted surgical procedures.

SEC61G regulates breast cancer cell proliferation and metastasis by affecting the Epithelial-Mesenchymal Transition.

Breast cancer is a common malignant tumor for women and its incidence has increased constantly in recent decades. The underlying molecular means of breast tumorigenesis endure uncertain. With the sequencing expertise, we found that the SEC61G gene is overexpressed in tumor tissues. However, the biological function of SEC61G in breast malignancy has yet to be determined. We investigated the SEC61G expression level, genetic alteration, IHC, immune infiltration, diagnostic value, survival analysis, and functional enrichment analysis by bioinformatics analysis. Then, vitro experiments were done. We investigated that SEC61G was greater in breast cancer tissues related to adjacent non-tumor tissues through qRT-PCR. We performed proliferation, colony formation, migration, invasion assays, and EMT-related phenotype to determine the specific biological functions of SEC61G in breast cancer cell lines (MDA-MB-231, BT-549) transfected with small interfering RNA. SEC61G expression and exon expression were higher in the tumor while the level of SEC61G methylation was higher in normal tissues. The expression level of SEC61G was connected with immune infiltration and survival and was an effective diagnostic and prognostic indicator. The functional enrichment analysis of SEC61G prompted that SEC61G might play a tumor-promoting role via the EMT pathway. In vitro experiments indicated that knocking down SEC61G considerably impaired the colony formation, cck-8, migration, and invasion, and induced apoptosis of the breast cancer cell lines. The vitro experiments also indicated that ectopic expression of SEC61G could influence EMT. This study revealed that SEC61G plays vital tumorigenic functions and acts as a novel oncogene in breast cancer.

BRCA1/BRCA2 mutation spectrum analysis in South Asia: a systematic review.

OBJECTIVE: Breast cancer (BC) is the most common form of cancer among Asian females. Mutations in the BRCA1/BRCA2 genes are often observed in BC cases and largely increase the lifetime risk of having BC. Because of the paucity of high-quality data on the molecular spectrum of BRCA mutations in South Asian populations, we aimed to explore these mutations among South Asian countries. METHODS: A systematic literature search was performed for the BRCA1 and BRCA2 gene mutation spectrum using electronic databases such as PubMed, EMBASE, and Google Scholar. Twenty studies were selected based on specific inclusion and exclusion criteria. RESULTS: The 185delAG (c.68_69del) mutation in exon 2 of BRCA1 was the most common recurrent mutation and founder mutation found. Various intronic variants, variants of unknown significance, large genomic rearrangements, and polymorphisms were also described in some studies. CONCLUSIONS: The South Asian population has a wide variety of genetic mutations of BRCA1 and BRCA2 that differ according to countries and ethnicities. A stronger knowledge of various population-specific mutations in these cancer susceptibility genes can help provide efficient strategies for genetic testing.

Preoperative prediction of lymph node metastasis in patients with papillary thyroid carcinoma by an artificial intelligence algorithm.

BACKGROUND: It is necessary to identify patients at risk of developing lymph node metastasis prior to papillary thyroid carcinoma (PTC) surgery. This can be challenging due to limiting factors, and an artificial intelligence algorithm may be a viable option. OBJECTIVE: In this study, we aimed to evaluate whether combining an artificial intelligence algorithm (support vector machine and probabilistic neural network) and clinico-pathologic data can preoperatively predict lymph node metastasis of papillary thyroid carcinoma (PTC). METHODS: We retrospectively examined 251 PTCs with lymph node metastasis and 194 PTCs without lymph node metastasis. The artificial intelligence algorithm included the support vector machine (SVM) and the probabilistic neural network (PNN). RESULTS: The ACR TI-RADS (Thyroid Imaging, Reporting and Data System), number of tumours, no well-defined margin, lymph node status and rim calcification on ultrasonography (US), age, sex, tumour size, and presence of Hashimoto's thyroiditis were significantly more frequent among PTCs with central lymph node metastasis than those without metastasis (P<0.05). The PNN classifier revealed an F1 score of 0.88 on the central lymph node metastasis test set. The SVM classifier revealed an F1 score of 0.93 on the lateral lymph node metastasis test set. Our study demonstrates that combining artificial intelligence algorithms and clinico-pathologic data can effectively predict the lymph node metastasis of papillary thyroid carcinoma prior to surgery.

Aberrant expression of WDR4 affects the clinical significance of cancer immunity in pan-cancer.

Recent publications have presented research showing that WD repeat domain 4 (WDR4) plays a significant role in various kinds of malignant tumours. However, the expression profile of WDR4 is still unspecified, as is its significance in the analysis of human pan-cancer. We conducted an in-depth analysis of three aspects of WDR4 expression patterns from 33 types of cancer and determined the value of WDR4 for prognostic prediction and carcinoma drug resistance prediction. WDR4 was expressed in different cancer cell lines at inconsistent levels. Aberrant expression of WDR4 has been observed in various malignant cancers and is significantly implicated in overall survival outcomes. The expression level of WDR4 is also strongly associated with tumour immunity, such as immune scores and tumour-infiltrating immune cells. The level of WDR4 is related to microsatellite instability and tumour mutation burden in several types of malignancy, and validation studies implied that WDR4-associated terms and pathways are involved in malignancy. We explored the expression level of WDR4 across 33 types of cancer and showed that WDR4 plays a significant role during cancer development. More crucially, WDR4 is associated with immune infiltration, which suggests that WDR4 could be an immunotherapy target in cancers. In summary, our research showed that WDR4 plays a vital role in tumorigenesis and has the potential for to be targeted with treatments.

Serum TSH levels are associated with postoperative recurrence and lymph node metastasis of papillary thyroid carcinoma.

OBJECTIVE: To explore the relationship between thyroid-stimulating hormone (TSH) levels in the serum and postoperative recurrence and lymph node metastasis (LNM) in papillary thyroid cancer (PTC) patients after surgery. METHODS: We selected 272 patients diagnosed with PTC from June 2011 to July 2014. The clinical and pathological data of 272 PTC patients were collected at the First Affiliated Hospital of Wenzhou Medical University and analysed retrospectively. All PTC patients were tested for the BRAFV600E gene mutation before surgery by fine-needle aspiration (FNA) cytology, and TSH levels in the serum were determined one month after surgery. The optimal cut-off value of thyroid-stimulating hormone (TSH) for predicting the recurrence or metastasis of PTC after surgery was determined by the establishment of a receiver operating characteristic (ROC) curve. Kaplan-Meier and Cox regression analyses were used to evaluate the correlation between the optimal cut-off value of TSH and disease-free survival rate and prognosis. RESULTS: Of 272 patients, only 182 (73 BRAFV600E+, 109 BRAFV600E-) met the final study criteria. Among them, 60 cases had recurrence or metastasis, and 122 cases were controls. The optimal cut-off value of TSH for the prediction of recurrence or metastasis of PTC after surgery was 2.615 mlU/L. In our study, a high TSH level (> 2.615 mlU/L) was correlated with the BRAFV600E mutation, multifocality, lymph node metastasis, recurrence, and metastasis. In all 182 patients, those with high TSH levels had worse disease-free survival. This result was more obvious in the 73 BRAFV600E+ patients. The univariate analysis showed that lymph node metastasis, multifocality, lymph node dissection, tumour size, sex, BRAFV600E mutation, and a high postoperative TSH level were all significantly correlated with recurrence or metastasis in PTC patients (all P < 0.05). In addition, the Cox multivariate analysis showed that lymph node metastasis, BRAFV600E mutation, and high postoperative TSH levels were independent risk factors for PTC recurrence or metastasis (all P < 0.05). CONCLUSION: PTC patients with high TSH levels (> 2.615 mlU/L) have worse disease-free survival, which is more obvious in the BRAFV600E+ population.

Factors associated with breast cancer screening intention in Kathmandu Valley, Nepal.

BACKGROUND: Breast cancer burden is increasing in low-income countries (LICs). Increasing incidence and delayed presentation of breast cancer are mainly responsible for this burden. Many women do not participate in breast cancer screening despite its effectiveness. Moreover, studies are limited on the barriers associated with low utilization of breast cancer screening in LICs. This study identified breast cancer screening behavior and factors associated with breast cancer screening intention among women in Kathmandu Valley, Nepal. METHODS: A cross-sectional study was conducted among 500 women living in five municipalities of Kathmandu Valley, Nepal. Data were collected from July to September 2018, using a structured questionnaire. Interviews were conducted among women selected through proportionate random household sampling. This study was conceptualized using the theory of planned behavior, fatalism, perceived susceptibility, and perceived severity. The outcome variables included: the intention to have mammography (MMG) biennially, the intention to have clinical breast examination (CBE) annually, and the intention to perform breast self-examination (BSE) monthly. Analysis was conducted separately for each outcome variable using partial proportional odds model. RESULTS: Out of 500 women, 3.4% had undergone MMG biennially, 7.2% CBE annually, and 14.4% BSE monthly. Women with a positive attitude, high subjective norms, and high perceived behavioral control were more likely to have the intention to undergo all three screening methods. Similarly, women were more likely to have intention to undergo CBE and MMG when they perceived themselves susceptible to breast cancer. Conversely, women were less likely to have intention to undergo CBE when they had high fatalistic beliefs towards breast cancer. CONCLUSION: Women in this study had poor screening behavior. The practice of breast self-examination was comparatively higher than clinical breast examination and mammography. Multidimensional culturally sensitive interventions are needed to enhance screening intentions. Efforts should be directed to improve attitude, family support, and fatalistic belief towards cancer. Furthermore, the proper availability of screening methods should be ensured while encouraging women to screen before the appearance of symptoms.

Pan-cancer investigation of CENPK gene: clinical significance and oncogenic immunology.

Many studies have confirmed that the CENPK gene regulates the progression of cancers, but its specific molecular mechanism remains unidentified, as does its significance in the analysis of human cancers. We specify a comprehensive genomic architecture of the CENPK gene associated with the tumor immune microenvironment and its clinical relevance across a broad spectrum of solid tumors. Statistics from The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia (CCLE) of over 30 solid tumors were examined. CENPK was expressed differentially in several cancers and is significantly associated in survival outcomes, with higher CENPK signifying a worse prognosis for ACC, KICH, KIRC, KIRP, LGG, LIHC, LUAD, MESO, and SARC. We further examined its clinical relevance with tumor immunogenic features. The expression level of CENPK was not only strongly linked to the tumor infiltration, such as tumor-infiltrating immune cells and immune scores but also linked to microsatellite instability and tumor mutation burden in diverse cancers (P<0.05). I mmune markers such as TNFRSF14 and VSIR were highly expressed on over 20 kinds of human cancer and mismatch repair genes like MLH1, MSH2, MSH6, and PMS2 were positively related with CENPK expression. Moreover, the methyltransferases and functional pathways also seem to have a relationship with the CENPK. CENPK is expected to be a guiding marker gene for clinical prognosis and tumor personalized immunotherapy.

Age of individuals undergoing cleft lip and cleft palate surgeries in Nepal.

INTRODUCTION: Timely repair of cleft lip and palate maximises the benefits of surgery. Developing countries have large number of adults with unrepaired clefts. The impact of a cleft program can be determined by observing the trends of lower age at surgery. Public Health Concern Trust, Nepal has been providing a comprehensive nationwide cleft service since 1999. This study was conducted to see any change in the age at surgery. METHODS: A retrospective cross sectional study was conducted to analyse the data of all the individuals' age at primary cleft surgery from July 1999 to June 2010. Mean and median age of individuals as well as the proportion of individuals operated on at the right age in different years were calculated and compared. RESULTS: The median age for cleft lip surgery decreased from 100 to 24 months. Similarly the median age for cleft palate surgery decreased from 70 to 28 months. Proportion of surgeries carried out in the recommended age also increased. A change in the policy of the program reaching out to more remote areas and removing the age barrier for surgery resulted in older adults receiving surgery and increased median age especially for cleft palate repairs. CONCLUSIONS: A nationwide cleft program for a decade had a small impact on age at surgery. There are still many individuals who are missing the ideal age for surgery. The program needs to reach more remote areas. This information will be useful for governmental as well as non-governmental organizations working in the area of clefts.