Risk Of Squamous Cell Carcinoma Research Articles

The impact of ERP29 on the progression of pharyngeal squamous cell carcinoma

ERP29 gene encodes a chaperone protein critical for protein folding and secretion. Previous study linked ERP29 inhibition to an elevated risk of pharynx squamous cell carcinoma (PSCC) and reduced patients’ survival. However, ERP29 role in PSCC progression remains unknown. Here, we investigated ERP29 impact on PSCC progression in cisplatin (CDDP)-sensitive (FaDu and LAU-2063), CDDP-treated (FaDu-CDDP), and CDDP-resistant (FaDu-R) cells. ERP29 silencing decreased necrosis and increased migration in CDDP-sensitive, treated, and resistant cells; and reduced E-cadherin and increased vimentin immunoexpression in CDDP-sensitive 3D-spheroids. During CDDP treatment, ERP29 silencing enhanced proliferation. In CDDP-sensitive cells, ERP29 silencing upregulated genes associated with WNT, MAPK, and PI3K/AKT signaling pathways while downregulating CASP9 expression. During CDDP treatment, ERP29 silencing downregulated MDM2 and CASP9 expression. In CDDP-resistant cells, ERP29 silencing upregulated SOS1, MAPK1, AKT1, ITGAV, and CCNE1, while downregulating KRAS, JUN, MDM2, and CASP9 expression. In addition, inhibition of microRNA miR-4421 increased ERP29 expression and decreased MAPK1, AKT1, and JUN expression in CDDP-sensitive cells, as well as SOS1, MAPK1, AKT1, and ITGAV in CDDP-resistant cells. Lower ERP29 and higher miR-4421 expressions were predictive of poor survival, suggesting a potential therapeutic use for miR-4421 inhibitors. Upon validation, these findings may contribute to targeted therapies for PSCC based on ensuring ERP29 expression.

Males Have Lower Anal Pap Smear Screening in a Miami Safety-Net HIV Clinic.

Although people with HIV have a markedly higher risk of anal squamous cell carcinoma (ASCC), there are few evaluations of anal Pap screening determinants within safety-net HIV clinics. We conducted an evaluation of anal Pap screening correlates within a safety-net HIV clinic in Miami. Medical records were reviewed for 298 people ages 45 and older receiving HIV primary care. Demographic information and the prevalence of anal Pap screening over 1year (i.e., 2018-2019) were extracted. Between 2018 and 2019, approximately half (46%) of patients completed anal Pap screening although this varied by sex assigned at birth. More than three-fourths of females (77%) compared to one-fourth (23%) of males were screened between 2018 and 2019 (p < 0.0001). Findings underscore the need for multi-level intervention approaches to optimize anal Pap screening among maleswith HIV within the Miami-basedsafety-net clinic.

Hydrochlorothiazide Use and Risk of Skin Cancer: A Population-Based Retrospective Cohort Study.

Hydrochlorothiazide (HCTZ) exposure has been linked to increased skin cancer in Caucasian (white) populations, especially squamous cell carcinoma (SCC), but not basal cell carcinoma (BCC). This study aimed to evaluate and compare skin cancer risks associated with HCTZ- and other antihypertensives use. This retrospective cohort study utilized Taiwan's National Health Insurance Research Database. We identified patients aged 20 years and older, newly receiving antihypertensive medications between 2004 and 2015. We calculated the medication possession ratio (MPR) for the first 2 years of treatment to determine patient eligibility and treatment classification, whereby only patients with MPR above 80% were included. These were subsequently categorized by the type of antihypertensives they received, namely HCTZ, other thiazide diuretics, non-thiazide diuretics or non-diuretic antihypertensives. Cox proportional hazards model was used to evaluate skin cancer risks, and these were then classified as SCC or BCC. Our study included 41 086, 27 402, 19 613, and 856 782 patients receiving HCTZ, other thiazide diuretics, non-thiazide diuretics, and non-diuretic antihypertensives, respectively. We found BCC risks were similar when comparing HCTZ with other thiazides (adjusted hazard ratio: 0.84; 95% CI: 0.54-1.33), non-thiazide diuretics (0.93; 0.51-1.67), and non-diuretic antihypertensives (0.91; 0.66-1.26). We observed a higher SCC risk in the HCTZ group, compared to other thiazides (1.24; 0.74-2.08), non-thiazide diuretics (1.32; 0.70-2.51), and non-diuretic antihypertensives (1.23; 0.87-1.73), although the confidence intervals (CIs) were wide and crossed the null. We concluded that skin cancer need not be of major concern to physicians when prescribing antihypertensives for an Asian population.

Exploring Epidermodysplasia Verruciformis: A Case Report, Treatment Strategies, and Emerging Therapies

Abstract Introduction/Objective Epidermodysplasia verruciformis (EV) is a rare cutaneous disorder with both inherited and acquired forms. Inherited cases involve mutations in genes such as ERV1 and ERV2, crucial for HPV immunity, while acquired cases affect immunocompromised individuals. EV is linked to cutaneous squamous cell carcinoma (SCC), highlighting the need for prompt diagnosis and treatment. Methods/Case Report A 54-year-old HIV-positive man was referred with a persistent, itchy eruption on his forearms despite given ARV regimen, oral retinoids and topical therapies. Physical examination revealed hypopigmentation and hyperkeratotic plaques on both forearms. Histologic examination revealed large cells with blue-gray cytoplasm and perinuclear halo in the upper epidermis, consistent with EV. Although advised for papilloma virus vaccination and planned for a trial of topical cidofovir, the patient was lost to follow-up. Treatment strategies for EV vary depending on lesion severity. Severe keratinized or precancerous lesions typically require surgical removal as the first-line approach. For early-stage EV with few small lesions, 5-FU, cidofovir, glycolic acid, and imiquimod is recommended. Tazarotene 0.5% cream used twice weekly has shown success in resolving lesions within 14 days. Topical imiquimod’s efficacy appears variable. In HIV-positive patients with EV, topical 1% cidofovir showed success in some cases. Systemic and topical retinoids are advised for diffuse lesions, with electrocautery or cryotherapy as options if initial treatments fail. HPV vaccination combined with oral acitretin, topical tretinoin and imiquimod led to lesion flattening. Continuous low-dose isotretinoin achieved prolonged remission of EV, but its efficacy in acquired EV remains unclear. Topical methyl aminolevulinate followed by photodynamic therapy has also shown promise. Results (if a Case Study enter NA) NA Conclusion Since its discovery in the 1970s, Acquired EV has been observed across diverse demographics, including HIV patients and organ transplant recipients. Advanced HPV typing and sequencing techniques aid in predicting SCC risk. Emerging treatments like topical cidofovir and combination therapies show promise, necessitating larger clinical trials for validation.

Analysis of Risk Factors with Assessment of the Impact of the Microbiome on the Risk of Squamous Cell Carcinoma of the Larynx.

Introduction: Head and neck squamous cell carcinoma (HNSCC) ranks sixth among cancers in the world, and the 5-year survival rate ranges from 25% to 60%. The risk factors for HNSCC are primarily smoking, alcohol consumption and human papillomavirus (HPV). Data indicate that 15-20% of cancers are caused by infectious agents, 20-30% by smoking and 30-35% by unhealthy lifestyles, diet, lack of physical activity and obesity. Dysbiosis is a microbiome imbalance, which promotes oncogenesis by intensifying inflammatory processes and affecting the host's metabolism. Profiling the microbiome in various types of cancer is currently the subject of research and analysis. However, there is still little information on the correlation of the microbiome with HNSCC and its impact on oncogenesis, the course of the disease and its treatment. Objective: The aim of the study was to prospectively assess risk factors with assessment of the impact of the microbiome on the risk of squamous cell carcinoma of the larynx. The study included a group of 44 patients diagnosed with squamous cell carcinoma of the larynx and 30 patients from the control group. Results: In the control group, bacteria of the normal microbiome dominated-the genus Streptococcus, Gemella, Neisseria and Kingella. In the group of patients with laryngeal cancer, Prevotella, Clostridiales and Stomatobaculum were found significantly more often. Porphyromonas, Fusobacterium, Lactobacillus, Actinobacteria, Actinomyces and Shaalia odontolytica were also found at a higher percentage in the study group. Analyzing the phylum, Firmicutes dominated in the control group; there were statistically significantly more of them than in patients from the study group. Bacteroides and Bacillota were found significantly more often in patients with laryngeal cancer. Conclusions: The importance of the microbiome in oncology has been confirmed in many studies. Independent risk factors for laryngeal cancer were primarily a lower number of Firmicutes in the microbiome, but also an increased leukocyte level above 6.52 × 103/mm and a decreased total protein level below 6.9 g/dL. Prevotella, Clostridiales, Stomatobaculum, Porphyromonas, Fusobacterium, Lactobacillus, Actinobacteria, Actinomyces and Shaalia were considered to be the bacteria contributing to the development of laryngeal cancer. Streptococcus, Gemella, Neisserie and Kingella were considered to be protective bacteria. Moreover, the study confirmed the significant impact of smoking, alcohol consumption and poor oral hygiene on the development of laryngeal cancer. The microbiome, its identification and manipulation may constitute a breakthrough discovery for improving the diagnosis and oncological therapy of laryngeal cancer, and also of the entire group of HNSCC. Profiling the microbiome may allow for personalized therapy related to its modification. Assessing the microbiome of patients diagnosed with cancer may provide an opportunity to predict treatment response and effectiveness.

Advanced Techniques In Oral Oncology: AComprehensiveReview

The most common type of oral cancer, oral squamous cell carcinoma (OSCC), is still amajor global health concern. Due to delayed diagnoses, which are frequently caused by low public awareness and fewscreeningalternatives, the five-year survival rate is still low. Modernmethods in oral oncology have arisen to enhance patient outcomes and early identification, including as molecular and imaging diagnostics. This review showcases several cutting-edge diagnostic techniques, including flow cytometry, next-generation sequencing(NGS), chemiluminescence, toluidine blue, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), and nano-diagnostics. By providing insights into tumor behaviourand enabling customized treatment approaches, these techniques advance our knowledge of the genetic and proteomic landscape of oral cancer. Combining these cutting-edge approaches with conventional diagnosticsmight greatly improve the accuracy of OSCC detection and risk assessment, despite drawbacks like false positives and expensive procedures. Improving patient care greatly depends on the creation of quick, noninvasive procedures and the investigation of genetic biomarkers. The present review highlightsthe need for continued research and training in oral oncology to maximize early diagnosis and intervention strategies

418 (PB406): Single nucleotide polymorphisms in microRNA genes associate with the risk of Oral Squamous Cell Carcinoma in Central Indian Population

418 (PB406): Single nucleotide polymorphisms in microRNA genes associate with the risk of Oral Squamous Cell Carcinoma in Central Indian Population

Expression of Programmed Death Ligand 1 and Indoleamine 2,3-Dioxygenase in Oral Lichen Planus and Oral Lichenoid Lesions.

Oral lichen planus (OLP) and oral lichenoid lesions (OLL) are inflammatory T-cell mediated disorders of the oral mucosa (OM). Both are associated with an increased risk of oral squamous cell carcinoma, with OLL possibly having a higher rate of malignant transformation than OLP. Programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO) are immunosuppressive molecules possessing inhibitory effect on T-cells and have been implicated in carcinogenesis. The aim of this study was to examine the expression of PD-L1 and IDO in OLP and OLL. Sixty-eight formalin-fixed, paraffin-embedded tissue samples diagnosed as OLP, compatible with OLP, or OLL were divided into OLP (n = 39) or OLL (n = 29) groups based on both clinical and histopathological diagnostic criteria. Samples of healthy OM (n = 9) served as controls. Samples were immunohistochemically stained for PD-L1 and IDO, and staining distribution and intensity were evaluated. Immunohistochemical expression of PD-L1 was increased in the basal and intermediate layers of epithelium in OLP and in lamina propria in both OLP and OLL compared to controls. OLP and OLL showed increased expression of IDO in epithelium and lamina propria compared to controls. PD-L1 staining intensity in the basal epithelial layer, and IDO staining intensity in lamina propria were increased in OLP compared to OLL. The results indicate that the expression of PD-L1 and IDO increases in OLP and OLL, suggesting that these molecules may play a role in the pathogenesis of both disorders.

The causal and mediation effect of chronic obstructive pulmonary disease on lung cancer subtypes: a two-sample mendelian randomization study.

This study aims to determine the causal effect of chronic obstructive pulmonary disease (COPD) on different subtypes of lung cancer and to investigate the mediation effects of COPD between smoking and the subtypes of lung cancer. The study utilized summary level data from genome-wide association studies. It extracted independent single nucleotide polymorphisms (SNP) to serve as instrumental variables (IV). We conducted two-sample MR analyses primarily using inverse-variance weighting, as well as MR-Egger and MR-PRESSO to establish and validate the causal impact of COPD on lung cancer subtypes. Additionally, multivariable MR analysis was employed to ascertain the mediating role of COPD between smoking and lung cancers. The two-sample MR analysis demonstrated that COPD is linked to an elevated risk of lung adenocarcinoma (OR: 1.48, 95% CI 1.35-1.61, p = 0.009) and squamous cell carcinoma (OR: 1.78, 95% CI 1.62-1.93, p = 0.001). Further, using multivariable MR, it was established that COPD mediates the causal effects of smoking on lung adenocarcinoma by 56.52% (95% CI 17.51-95.52%) and 63.61% (95% CI 38.31-88.92%) in lung squamous cell carcinoma. Our study found that COPD was a risk factor for developing both lung adenocarcinoma and squamous cell carcinoma. COPD also played a crucial role in mediating the causal effects of smoking on these two subtypes of lung cancer.

A case controlled study of risk factors for metastatic squamous cell carcinoma in organ transplant recipients: single academic medical center.

Solid organ transplant recipients (SOTRs) are at high risk of cutaneous squamous cell carcinoma (cSCC) metastasis. Despite prior studies identifying risk factors, mortality remains high. Understanding additional risk factors may aid in reducing mortality in this population. This study aimed to investigate risk factors and predictive variables for metastatic cSCC in SOTRs. The primary goal was to accurately identify transplant patients at increased risk of metastatic cSCC. A retrospective case-control study in a single institution of 3576 cases of organ transplants were identified from January 1991 to July 2022. A cohort of metastatic cancer patients and two randomly generated age and organ matched control cohorts were identified. 16 SOTR patients developed metastatic cSCC. The majority were male, with high-risk tumor sites. Tumor depth varied and half exhibited perineural invasion. Cylex® (p = 0.05) and white blood cell counts (p = 0.04) were significantly lower in these patients compared to control. Lung transplants were at highest risk relative to other solid organ transplants. Voriconazole exposure was also associated with increased metastatic risk (p = 0.04). Small sample size at a single institution. Close monitoring of SOTR, especially those with lung transplants given their increased risk, reducing immunosuppression, and limiting exposure to voriconazole can improve outcomes in SOTRs with metastatic cSCC.

Oral Lichen Planus: A Narrative Review Navigating Etiologies, Clinical Manifestations, Diagnostics, and Therapeutic Approaches.

Background/Objectives: Oral Lichen Planus (OLP) is a common immune-mediated inflammatory disorder affecting the oral mucosa, impacting 0.5% to 2% of the global population, primarily middle-aged women. Immunological dysregulation is a key factor in OLP's pathogenesis, involving CD4+ T helper and CD8+ T cytotoxic cells. The World Health Organization (WHO) classifies OLP as a potentially malignant disorder, with a risk of oral squamous cell carcinoma (OSCC) developing in up to 2% of lesions. This narrative review aims to provide a comprehensive overview of the etiopathogenesis, clinical manifestations, diagnostic criteria, and therapeutic strategies for OLP, informing clinical practice and guiding future research. Methods: A review of the literature from the PubMed and Google Scholar databases was conducted up to December 2023, focusing on studies addressing the etiopathogenesis, diagnosis, clinical manifestations, and treatment of OLP. Results: OLP's pathogenesis is driven by immune dysregulation, with CD4+ and CD8+ cells playing crucial roles. Clinically, OLP presents as reticular, erosive, bullous, and plaque-like lesions. Diagnosis relies on clinical examination, histopathology, and direct immunofluorescence. Recent advancements in diagnostic markers and imaging techniques have improved detection and monitoring. Treatment primarily involves corticosteroids, but novel therapies such as curcumin, retinoids, and laser therapy are increasingly used for their effectiveness and reduced side effects. These treatments show promise in symptom reduction and recurrence prevention, although long-term data are needed. Conclusions: Regular screenings and biopsies are essential due to OLP's likelihood of malignant transformation. This study urges further investigation into long-term results, improved diagnostic techniques, and evidence-based treatment regimens.

Assessment of LINC-PINT genetic polymorphisms and esophageal squamous cell carcinoma risk in the Hainan Han population

Objectives Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high incidence and mortality rates worldwide. This study aimed to investigate the correlation between LINC-PINT polymorphisms and ESCC risk in the Hainan Han population. Methods A total of 391 patients with ESCC and 452 healthy controls were enrolled to evaluate the effect of LINC-PINT SNPs (single nucleotide polymorphisms) on ESCC susceptibility. Associations were evaluated by calculating odds ratios (OR) and 95% confidence intervals (CIs). Multifactor dimensionality reduction analysis was performed to explore the association between SNP-SNP interactions and ESCC susceptibility. We further determined the correlation between clinical indicators and SNP in patients with ESCC. Results Our study showed that rs157916 (OR 0.63, p = 0.011) and rs157928 (OR 0.80, p = 0.021) were associated with a decreased risk of ESCC. Stratified analysis indicated that rs157916 could decrease the risk of ESCC in people aged >64 years, in males, and non-drinkers (OR 0.58, p = 0.042; OR 0.58, p = 0.010; OR 0.62, p = 0.025, respectively). Rs16873842 was related to a decreased risk of ESCC in males (OR 0.70, p = 0.015). Rs7801029 was associated with ESCC risk in females (OR 0.39, p = 0.033) and non-drinkers (OR 0.68, p = 0.040). Rs7781295 decreased the ESCC risk in smokers (OR 0.58, p = 0.046) and drinkers (OR 0.58, p = 0.046). In addition, rs157928 played a protective role in ESCC risk in females (OR 0.39, p = 0.033) and non-smokers (OR 0.32, p = 0.006). Additionally, the best predictive model for ESCC was a combination of rs157916, rs16873842, rs7801029, rs7781295, rs28662387, and rs157928. Conclusion Our study revealed that LINC-PINT polymorphisms were associated with ESCC risk.

No evidence that retinol is protective for skin cancer.

With over 1.5 million new cases annually, skin cancers are the most commonly diagnosed group of cancers worldwide. Among these, melanoma and keratinocyte cancers (KC), comprising squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), are predominant. Retinol, a vitamin A derivative, is essential in the regulation of growth and differentiation of epidermal cells. Moreover, retinol exhibits antioxidant properties, protecting the skin against ultra-violet (UV) radiation induced oxidative damage. Existing research on the impact of retinol on melanoma, SCC and BCC development shows mixed results. Several dietary intake studies have suggested that higher retinol levels reduce skin cancer risk, however, others have failed to find this association. We used two-sample Mendelian randomization (MR) to explore if there is a causal relationship between retinol and the risk of developing melanoma, SCC or BCC. Genetically predicted circulating retinol levels were obtained from a genome wide association study (GWAS) meta-analysis of the INTERVAL (N=11,132) and METSIM (N=6,136) cohorts. Melanoma (30,134 cases and 375,188 controls), SCC (10,557 cases and 537,850 controls) and BCC (36,479 cases and 540,185 controls) risks were derived from published GWAS meta-analyses. We conducted two MR approaches. In the first MR we used a single SNP (rs10882283) that is associated with the levels of Retinol Binding Protein 4 (RBP4) as an instrument variable (IV) for circulating retinol levels. In the second MR we used all independent genetic variants that were strongly associated (P < 5 × 10-8) with retinol levels as IVs. Odds ratios (OR) for skin cancer were calculated for a one standard deviation (SD) increase in genetically predicted retinol levels. The single IV approach revealed that retinol levels were not significantly associated with risk of melanoma (OR = 1.04 [95% confidence interval 0.83, 1.31], P = 0.72), SCC (OR = 1.15 [0.87, 1.51], P = 0.32) or BCC (OR = 1.06 [0.90, 1.23], P = 0.50). Similar null results were observed with the multiple IV approach for melanoma (OR = 1.03 [0.95, 1.11], P = 0.54), SCC (OR = 1.01 [0.91, 1.13], P = 0.83), and BCC (OR = 1.04 [0.96, 1.12], P = 0.38). In conclusion, we found no evidence that circulating retinol levels were causally associated with the development of melanoma, SCC and BCC.

Association between four insulin resistance surrogates and the risk of esophageal cancer: a prospective cohort study using the UK Biobank

PurposeThis study explored the association between triglyceride-glucose (TyG), TyG index with body mass index (TyG-BMI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), metabolic score for insulin resistance (IR) (METS-IR) and the risk of esophageal cancer.MethodsA total of 388,900 participants from the United Kingdom Biobank from 2006 to 2010 were included. Fine-Gray models, restricted cubic spline (RCS), and receiver operating characteristic (ROC) curves were used to assess the association between the four IR surrogates and the risk of esophageal cancer, specifically, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC).ResultsTen years after recruitment, 0.16% (95%CI 0.11–0.26%) had esophageal cancer and 4.17% (95%CI 3.86–4.46%) are deceased. For each standard deviation increase in the TyG index, TyG-BMI, TG/HDL-C, and METS-IR, the risk of EAC increased by Hazard ratios (HR)1.16, 1.37, 1.08, and 1.36, respectively (all P < 0.05), while the risk of ESCC decreased by HRs 0.80, 0.67, 0.77, and 0.65, respectively. RCS analysis indicated that most relationships were nonlinear (P < 0.05). ROC curves showed that METS-IR had a more robust diagnostic efficacy than TyG, TyG-BMI, and TG/HDL-C.ConclusionTyG index, TyG-BMI, TG/HDL-C, and METS-IR were closely associated with the risk of EAC and ESCC. Additionally, METS-IR surpassed the other three IR indices in predicting and diagnosing the risks of EAC and ESCC. The METS-IR is expected to become a more effective metric for identifying populations at early risk of esophageal cancer and for improving risk stratification.

Assessment of Prognostic Indicators and Survival-Based Impact of Holistic Approach in Oral Cancer Patients: An Observational Study.

Oral cancer is recognized as the sixth most common type of cancer globally. Instances have been recorded demonstrating an increase in its incidence, particularly in the territories of southern Asia, with a significant emphasis on India.Thus, the objectives of this investigation were to assess the efficacy of a holistic approach on the life expectancies of patients diagnosed with oral cancer, and to assess the prognostic indicators in such patients. A retrospective study was conducted on medical records of 60 clinically and histopathologically confirmed cases of oral squamous cell carcinoma (OSCC) who received complete surgical intervention or radiation therapy or a combination of both modalities depending on stage of OSCC from January 2015 to December 2016. After completion of their treatment, 30 patients underwent Cancer Care program of Annabhai Chudamani Patil Memorial Medical College which consisted of yoga sessions, meditation, psychological counselling, nutritional counselling, emotional and social support (embracing a holistic approach, group 1) and 30 patients did not enroll in the Cancer Care initiative (not opting for holistic approach, group 2). The program was conducted for 21 days every six months for two years. Data pertaining to demographic characteristics, stage of OSCC, modalities of treatment administered, histopathological characteristics of the neoplasm, as well as the clinical outcome (Survival/Deceased) post a five-year duration subsequent to the primary diagnosis were extracted from the medical records to assess the role of holistic approach and various factors on the overall survival (OS) of the patients in both the groups. The data collected was subsequently subjected to a thorough statistical analysis. The mean age of the patients was 44.33±8.66 years (95% CI: 39.53-49.13) in group 1, and 51.20±9.99 years (95% CI: 39.53-49.13) in group 2. The mean survival time for group 1 was 81.60±5.02 months (95% CI: 78.817-84.383), and 66.00±20.29 months (95% CI: 54.761-77.239) in group 2 with statistically significant difference between the groups (p=0.007). Group 2 showed a 1.31 relative risk of mortality to group 1. The probability of death in group 2 was 1.39 times more than in group 1. Cox regression analysis revealed group 2 was significantly associated with the risk of OSCC in this analysis. Other variables were not significantly associated with the risk of the OSCC in this analysis. The current research indicated that employing a holistic strategy proves to be a successful approach in increasing the OS of patients with OSCC.

Causal associations of plasma proteins with lung squamous cell carcinoma risk: a proteome-wide Mendelian randomization and colocalization analysis

BackgroundLung squamous cell carcinoma (LUSC) is a major subtype of non-small cell lung cancer with a high mortality rate. Identifying causal plasma proteins associated with LUSC could provide new insights into the pathophysiology of the disease and potential therapeutic targets. This study aimed to identify plasma proteins causally linked to LUSC risk using proteome-wide Mendelian randomization (MR) and colocalization analyses.MethodsProteome-wide MR analysis was conducted using data from the UK Biobank Pharma Proteomics Project and deCODE genetics. Summary-level data for LUSC were obtained from the ILCCO Consortium, the FinnGen study, and a separate GWAS study. A total of 1,046 shared protein quantitative trait loci (pQTLs) were analyzed. Sensitivity analyses included the HEIDI test for horizontal pleiotropy and colocalization analysis to validate the causal associations.ResultsMR analysis identified six plasma proteins associated with LUSC risk: HSPA1L, PCSK7, POLI, SPINK2, TCL1A, and VARS. HSPA1L (OR = 0.47; 95% CI: 0.34–0.65; P = 4.89 × 10–6), SPINK2 (OR = 0.68; 95% CI: 0.58–0.80; P = 3.17 × 10–6), and VARS (OR = 0.44; 95% CI: 0.31–0.63; P = 5.94 × 10–6) were associated with a decreased risk of LUSC. Conversely, PCSK7 (OR = 1.37; 95% CI: 1.21–1.56; P = 1.40 × 10–6), POLI (OR = 4.50; 95% CI: 2.25–9.00; P = 2.13 × 10–5), and TCL1A (OR = 1.72; 95% CI: 1.34–2.21; P = 1.89 × 10–5) were associated with an increased risk. The SMR analysis and HEIDI test confirmed the robustness of these associations. HSPA1L, SPINK2, and VARS showed significant inverse associations, with strong colocalization evidence for TCL1A (PPH4 = 0.817).ConclusionsThis study identified six plasma proteins potentially causal for LUSC risk. HSPA1L, SPINK2, and VARS are associated with decreased risk, while PCSK7, POLI, and TCL1A are linked to increased risk. These findings provide new insights into LUSC pathogenesis and highlight potential targets for therapeutic intervention.

Correlation between serum heavy metals and the risk of oral squamous cell carcinoma and oral potentially malignant disorders

Oral squamous cell carcinoma (OSCC) is a serious public health problem in various Asian countries, including Sri Lanka, and a combination of cultural practices, lifestyle factors, and genetic predispositions influences the incidence of these cancers. The examination of the connection between exposure to heavy metals and the probability of developing oral potentially malignant disorders (OPMD) and OSCC has been limited in its scope, and the overall consequences of such exposure remain largely unknown. This study aims to clarify the link between serum levels of heavy metals and the risk of OSCC and OPMD. The concentrations of seven heavy metals—namely, arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), lead (Pb), and zinc (Zn)—were analyzed in serum samples from 60 cases and 15 controls in the Sri Lankan cohort. The Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) was used for the analysis. Subsequently, the data underwent statistical evaluation via the Kruskal–Wallis H test, using the Statistical Package for Social Sciences (SPSS) version 28 software, with a confidence interval set at 95%. A p-value less than 0.05 was considered statistically significant. The cohort consisted of 48 men and 27 women, with 15 patients each diagnosed with OSCC, OSF, OLK, and OLP, and 15 healthy controls. The study used the Kruskal–Wallis Test to compare metal concentrations across groups, finding significant differences for all metals except As and Pb. Significant associations were observed between age, past medical history, drug history, gender, smoking, alcohol consumption, and betel chewing. The Spearman Correlation test showed significant correlations between the concentrations of Cr, Co, Cu, As, and Zn and the presence of cancer/precancer conditions. The study’s findings suggest that heavy metal contamination may be linked to the development of OSCC and precancerous conditions. When comparing OSCC and OPMD cases with controls, the serum concentrations of As and Pb did not differ significantly. However, Cd, Cr, Co, Cu, and Zn exhibited significantly higher concentrations among cases compared to controls (p < 0.05). This study observed significant variations in the levels of these five heavy metals among cancerous (OSCC), premalignant (OPMD), and healthy tissues, suggesting a potential role in the progression of malignancies. These findings underscore the importance of environmental pollution in this specific context.

Food biodiversity and gastrointestinal cancer risk in nine European countries: Analysis within a prospective cohort study

BackgroundFood biodiversity in human diets has potential co-benefits for both public health and sustainable food systems. However, current evidence on the potential relationship between food biodiversity and cancer risk, and particularly gastrointestinal cancers typically related to diet, remains limited. This study evaluated how dietary species richness (DSR) was associated with gastrointestinal cancer risk in a pan-European population. MethodsAssociations between DSR and subsequent gastrointestinal cancer risk were examined among 450,111 adults enrolled in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC, initiated in 1992), free of cancer at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires. DSR of an individual’s yearly diet was calculated based on the absolute number of unique biological species in each food and drink item. Associations between DSR and cancer risk were assessed by multivariable Cox proportional hazards regression models. FindingsDuring a median follow-up time of 14.1 years (SD=3.9), 10,705 participants were diagnosed with gastrointestinal cancer. Hazard ratios (HRs) and 95 % confidence intervals (CIs) comparing overall gastrointestinal cancer risk in the highest versus lowest quintiles of DSR indicated inverse associations in multivariable-adjusted models [HR (95 % CI): 0.77 (0.69–0.87); P-value < 0·0001] (Table 2). Specifically, inverse associations were observed between DSR and oesophageal squamous cell carcinoma, proximal colon, colorectal, and liver cancer risk (p-trend<0.05 for all cancer types). InterpretationGreater food biodiversity in the diet may lower the risk of certain gastrointestinal cancers. Further research is needed to replicate these novel findings and to understand potential mechanisms.

Role of diet in the risks of esophageal adenocarcinoma and squamous cell carcinoma: an updated umbrella review.

This updated umbrella review aimed to evaluate the evidence regarding the associations between dietary factors and the risks of esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). The PubMed, Embase, Cochrane Library, and Web of Science databases were searched to identify relevant studies. The quality of the included meta-analyses was evaluated using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). For each association, the number of cases, random effects pooled effect size, 95% confidence intervals (CIs), heterogeneity, 95% prediction interval (PrI), small-study effect, and excess significance bias were recalculated to determine the evidence level. We identified 33 meta-analyses describing 58 dietary factors associated with ESCC and 29 meta-analyses describing 38 dietary factors associated with EAC. There was convincing evidence regarding the association of 2 dietary factors (areca nut and high alcohol) with the risk of ESCC. There was highly suggestive evidence regarding the association of only 1 dietary factor (healthy pattern) with the risk of ESCC. There was suggestive evidence regarding the association of 11 dietary factors with the risk of ESCC, including fruit, citrus fruit, vegetables, pickled vegetables, maté tea, moderate alcohol, hot beverages and foods, hot tea, salt, folate, and vitamin B6. There was convincing evidence regarding the association of one dietary factor (vitamin B6) with the risk of EAC. There was suggestive evidence regarding the association of 4 dietary factors with the risk of EAC, including processed meat, dietary fibre, carbohydrate, and vitamin B12. The convincing evidence regarding the associations between dietary factors and the risks of ESCC and EAC remained robust in sensitivity analyses. This umbrella review highlighted convincing evidence regarding the associations of areca nut and high alcohol with a higher risk of ESCC. Additionally, an association between vitamin B6 and a decreased risk of EAC was observed. Further research is needed to examine the dietary factors with weak evidence regarding their associations with ESCC and EAC.

Single-cell transcriptome analysis deciphers the CD74-mediated immune evasion and tumour growth in lung squamous cell carcinoma with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) contributes to the incidence and prognosis of lung cancer. The presence of COPD significantly increases the risk of lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immune-inhibitory factors in T cells, although the mechanisms remain unclear. In this study, we aimed to decipher the tumour microenvironment signature for LSCC with COPD at a single-cell level. We performed single-cell RNA sequencing on tumour tissues from LSCC with or without COPD, then investigated the features of the immune and tumour cells. We employed multiple techniques, including multispectral imaging, flow cytometry, tissue microarray analysis, survival analysis, co-culture systems and in vitro and in vivo treatment experiments, to validate the findings obtained from single-cell analyses. LSCC with COPD showed increased proportions of tumour-associated macrophages (TAMs) and higher levels of CD8+ T cell exhaustion molecules, which contributed to an immunosuppressive microenvironment. Further analysis revealed a critical cluster of CD74+ tumour cells that expressed both epithelial and immune cell signatures, exhibited a stronger capacity for tumorigenesis and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by TAMs from LSCC with COPD may promote the activation of CD74. MIF-CD74 may interact with CD8+ T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-programmed cell death-1 ligand 1 signalling pathway, facilitating tumour proliferation and immune evasion. Our comprehensive picture of the tumour ecosystem in LSCC with COPD provides deeper insights into relevant immune evasion mechanisms and potential targets for immunotherapy. Our results demonstrated higher proportions of tumour-associated macrophages (TAMs) and higher levels of exhaustion molecules in CD8+ T cells in the microenvironment of LSCC with COPD. CD74+tumour cells were associated with poor disease prognosis. Migration inhibitory factor (MIF)-CD74 may interact with CD8+ T cells and impair their anti-tumour activity by regulating the PI3K-STAT3-PD-L1 signalling pathway, facilitating immune evasion.