Global burden of non-optimal temperature attributable stroke: The long-term trends, population growth and aging effects.

Since the 20th century, the world has undergone climate change, population growth and population aging, which may result in alterations in the epidemiology of non-optimal temperature-associated strokes. We employed multiple methodologies and data from the global burden of disease 2019 to unveil the long-term curvilinear trends in strokes attributed to non-optimal temperature and the impact of aging and population growth on its changing epidemiology. From 1990 to 2019, the age-standardized DALYs rate (ASDR) of strokes attributable to low temperature had been decreasing, but from 2016, the continued downward trend in ASDR disappeared and began to remain stable. On the contrary, the ASDR of strokes attributable to high temperature continued to increase. The high socio-demographic index (SDI) region experienced the fastest decreased trend. The disease burden of stroke attributable to low temperature is increased by aging in 178 countries (87.25%), compared with 130 (63.73%) for high temperature. After excluding aging and population growth, the DALY rate for strokes attributed to high temperature was increasing in 87 countries and territories (42.64%). The disease burden of strokes attributed to low temperature is far greater than that of high temperature in absolute figures. However, globally, there is a significant trend toward an increase in strokes attributed to high temperature. Social development has largely offset the burden of strokes attributed to low temperature, but most regions of the world are equally affected by strokes attributed to high temperature. Simultaneously, in the framework of climate change, aging is also largely hindering stroke prevention efforts.

Utilizing daily excessive concentration hours to estimate small for gestational age infants attributable to fine particulate matter in Wuhan, China.

Limited studies in China have explored the association between gravidae exposure to PM2.5 and small for gestational age infants (SGA), yielding inconsistent results. This study in Wuhan utilized daily excessive concentration hours (DECH) as a novel measure to assess PM2.5's impact on SGA. Data on air pollutants and pregnant women were collected from the Wuhan Municipal Ecology and Environmental Bureau and Wuhan Children's Hospital, respectively. Logistic regression models were employed to evaluate the contribution of PM2.5-DECH and PM2.5-mean to SGA. Significant correlations were observed between PM2.5-mean and SGA during the second trimester [OR = 1.23 (95% CI: 1.14-1.32)] and the entire pregnancy [OR = 1.15 (95% CI: 1.07-1.24)]. Similar correlations were found between PM2.5-DECH and SGA. These findings suggest that increased PM2.5 exposure is associated with a higher risk of SGA, and DECH may be used as a prospective substitute indicator for daily average concentration in similar studies.

Long-term exposure to air pollution might decrease bone mineral density T-score and increase the prevalence of osteoporosis in Hubei province: evidence from China Osteoporosis Prevalence Study.

We hypothesized that air pollution could cause oxidative damage and inflammation in the human body, which was linked to bone loss. Our result showed that long-term exposure to air pollution might decrease bone mineral density (BMD) T-score and increase the prevalence of osteoporosis in Hubei province. INTRODUCTION: Osteoporosis is becoming an increasingly serious public health problem with the advent of global aging. Long-term exposure to air pollution has been linked to multitudinous adverse health outcomes, but evidence is still relatively limited and inconsistent for BMD T-score and osteoporosis. This study aimed at exploring the associations between long-term exposure to air pollution and BMD T-score and osteoporosis. METHODS: The Hubei part of the China Osteoporosis Prevalence Study was extracted. Data on air pollutants were collected by the national air quality real-time release platform of China Environmental Monitoring Station. Linear mixed models and multilevel logistic regression analyses were performed to assess the associations between air pollution and BMD T-score and osteoporosis, respectively. Subgroup analyses were conducted to identify vulnerable populations. RESULTS: A total of 1845 participants were included in this cross-section study. Per 10 ug/m3 increase in PM2.5 and SO2 were associated with 0.20 (95% CI: 0.04, 0.36) and 0.31 (95% CI: 0.11, 0.51) decrease in BMD T-score of the neck of femur, respectively. Per 10 ug/m3 increase in CO was linked with 0.03 (95% CI: 0.02, 0.05) decrease in BMD T-score of the total hip. Per 1 ug/m3 increase in PM2.5 was associated with 5% increase in the prevalence of osteoporosis in all participants. In general, the higher concentrations of PM2.5 with the more adverse effect on osteoporosis (P for trend = 0.01). The impact of PM2.5 on osteoporosis in males was higher than that in females [1.29, 95% CI (1.11, 1.50) vs 1.01, 95% CI (0.95, 1.07)]. Per 1 ug/m3 increase in PM10 corresponded with 4% elevation in the risks of osteoporosis in rural population. The ORs (95% CI) for the association of osteoporosis and NO2 in ever/current smoking and drinking population were 1.07 (1.01, 1.13) and 1.05 (1.00, 1.09), respectively. SO2 had a statistically significant positive effect on people with comorbidity [OR = 1.10, (95% CI: 1.00 to 1.21)], while none in people without comorbidity [OR = 0.96, (95% CI: 0.88 to 1.05)]. CONCLUSION: Our study provided evidence that long-term exposure to PM2.5 was linked with the decreased BMD T-score and increased risk of osteoporosis among all participants. The adverse impacts of PM2.5, PM10, and NO2 were larger in males than in females. People having comorbidity, living in rural areas, and current/ever smoking or drinking were more vulnerable to air pollution. Public health departments should consider air pollution to formulate better preventive measures for osteoporosis.

Rs11655237 polymorphism of LINC00673 affects the prognosis of cervical cancer by interfering with the interaction between LINC00673 and microRNA-1231.

Single-nucleotide polymorphism (SNP) in long noncoding RNAs (lncRNAs) is known to disrupt the binding between lncRNAs and microRNAs. In this paper, we aimed to explore the role of LINC00673 rs11655237 SNP in the survival of cervical cancer (CC). Real-time polymerase chain reaction and western-blot analysis were used to detect expressions of LINC00673 and microRNA-1231 (miR-1231) in CC patients with different rs11655237 SNP genotypes. And the expression of LINC00673, miR-1231, and IFNAR1 was measured in mice and cells treated with exosomes carrying GG, GA, and AA rs11655237 genotypes. Compared with patients carrying the rs11655237 A allele of LINC00673 rs11655237 SNP, patients carrying the G allele showed higher overall survival and higher miR-1231 expression. In addition, the expression of miR-1231 was the highest in patients carrying the GG genotype and the lowest in patients carrying the AA genotype. Furthermore, the exosomes carrying GG, GA, and AA genotypes of LINC00673 rs11655237 SNP reduced tumor growth in mice, while the inhibitory effect of rs11655237 A allele was much stronger than that of the rs11655237 G allele. Additionally, exosome treatment upregulated the expression of LINC000673 and IFNAR1 while downregulating the expression of miR-1231. Interestingly, the A allele of rs11655237 generated a binding site for miR-1231 and subsequently affected the expression of IFNAR1, a target gene of miR-1231 containing a miR-1231 binding site in its 3'-untranslated region. Cells transfected with exosomes carrying GG, GA, and AA genotypes of LINC00673 rs11655237 SNP achieved higher LINC000673 and IFNAR1 expression along with lower miR-1231 expression. Therefore, rs11655237 can be used as a prognostic biomarker for CC.

Comprehensive landscape of extracellular vesicle-derived RNAs in cancer initiation, progression, metastasis and cancer immunology.

Extracellular vesicles (EVs), a class of heterogeneous membrane vesicles, are generally divided into exosomes and microvesicles on basis of their origination from the endosomal membrane or the plasma membrane, respectively. EV-mediated bidirectional communication among various cell types supports cancer cell growth and metastasis. EVs derived from different cell types and status have been shown to have distinct RNA profiles, comprising messenger RNAs and non-coding RNAs (ncRNAs). Recently, ncRNAs have attracted great interests in the field of EV-RNA research, and growing numbers of ncRNAs ranging from microRNAs to long ncRNAs have been investigated to reveal their specific functions and underlying mechanisms in the tumor microenvironment and premetastatic niches. Emerging evidence has indicated that EV-RNAs are essential functional cargoes in modulating hallmarks of cancers and in reciprocal crosstalk within tumor cells and between tumor and stromal cells over short and long distance, thereby regulating the initiation, development and progression of cancers. In this review, we discuss current findings regarding EV biogenesis, release and interaction with target cells as well as EV-RNA sorting, and highlight biological roles and molecular mechanisms of EV-ncRNAs in cancer biology.

Roles of miR-200 family members in lung cancer: more than tumor suppressors.

miRNAs are a class of single-stranded noncoding RNAs, which have no coding potential, but modulate many molecular mechanisms including cancer pathogenesis. miRNAs participate in cell proliferation, differentiation, apoptosis, as well as carcinogenesis or cancer progression, and their involvement in lung cancer has been recently shown. They are suggested to have bidirectional functions on important cancer-related genes so as to enhance or attenuate tumor genesis. Epithelial-mesenchymal transition (EMT) is a fundamental process which contributes to integrity of organogenesis and tissue differentiation as well as tissue repair, organ fibrosis and the progression of carcinoma, and several miRNAs were suggested to form the network regulating EMT in lung cancer, among which, miR-200 family members (miR-200a, miR-200b, miR-200c, miR-429 and miR-141) play crucial roles in the suppression of EMT.

CDK3 is a major target of miR-150 in cell proliferation and anti-cancer effect.

MiR-150, a member of small non-coding RNAs, has been proven to dysregulate in different types of tumor and bear on carcinogenesis and cancer prognosis by regulating the expression of a series of gene including utrophin. Given that utrophin can compensate for dystrophin's absence and be regarded as a promising therapeutic target for Duchenne Muscular Dystrophy (DMD), we further detected the deep role of miR-150 in dystrophic muscle. Using a range of bioinformatic, molecular and cell biology techniques, we declared that miR-150 directly targets cyclin-dependent kinase 3 (CDK3) and leads to the regulation of CDK3 gene expression in both muscle-derived and non-muscle cells. The results indicated the expression of miR-150 was upregulated in mdx muscle and closely related to the lower level of CDK3. Transient transfection of miR-150 into cultured C2C12 cells led to significant decrease in cell proliferation, which is partly mediated via the 3'-UTRs of CDK3 mRNA. Targeting of CDK3 could also play a role, at least in part, in the anti-cancer activity suggested for miR-150 in previous studies. Consistently, the analysis of tumor and matched normal lung tissues indicates that miR-150 downregulation in lung tumors correlates with higher CDK3 levels. In addition, miR-150 transfection experiments with cancer-derived cell lines reveal that miR-150-mediated CDK3 suppression directly induces to growth inhibition. Collectively, our results highlight a novel activity for CDK3 in myoblast cell proliferation and confirm CDK3 as a key target that further enhances the tumor suppressor function proposed for miR-150.

Sulforaphane Attenuates Muscle Inflammation in Dystrophin-deficient mdx Mice via NF-E2-related Factor 2 (Nrf2)-mediated Inhibition of NF-κB Signaling Pathway.

Inflammation is widely distributed in patients with Duchenne muscular dystrophy and ultimately leads to progressive deterioration of muscle function with chronic muscle damage, oxidative stress, and reduced oxidative capacity. NF-E2-related factor 2 (Nrf2) plays a critical role in defending against inflammation in different tissues via activation of phase II enzyme heme oxygenase-1 and inhibition of the NF-κB signaling pathway. However, the role of Nrf2 in the inflammation of dystrophic muscle remains unknown. To determine whether Nrf2 may counteract inflammation in dystrophic muscle, we treated 4-week-old male mdx mice with the Nrf2 activator sulforaphane (SFN) by gavage (2 mg/kg of body weight/day) for 4 weeks. The experimental results demonstrated that SFN treatment increased the expression of muscle phase II enzyme heme oxygenase-1 in an Nrf2-dependent manner. Inflammation in mice was reduced by SFN treatment as indicated by decreased infiltration of immune cells and expression of the inflammatory cytokine CD45 and proinflammatory cytokines tumor necrosis factor-α, interleukin-1ß, and interleukin-6 in the skeletal muscles of mdx mice. In addition, SFN treatment also decreased the expression of NF-κB(p65) and phosphorylated IκB kinase-α as well as increased inhibitor of κB-α expression in mdx mice in an Nrf2-dependent manner. Collectively, these results show that SFN-induced Nrf2 can alleviate muscle inflammation in mdx mice by inhibiting the NF-κB signaling pathway.

MicroRNA-187-3p mitigates non-small cell lung cancer (NSCLC) development through down-regulation of BCL6.

Hsa-microRNA-187-3p (miR-187-3p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-187-3p on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-187-3p on the development of NSCLC. The results indicated that miR-187-3p was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-187-3p in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay and colony formation assay, through inhibition of BCL6. In addition, miR-187-3p induced apoptosis, as indicated by concomitantly with up-regulation of the activities of caspase-3 and caspase-7, and inhibited cellular migration and invasiveness through inhibition of BCL6. Further, oncogene BCL6 was revealed to be a putative target of miR-187-3p, which was inversely correlated with miR-187-3p expression in NSCLC. Taken together, our results demonstrated that miR-187-3p played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic BCL6.

Red Meat Consumption and the Risk of Stroke: A Dose-Response Meta-analysis of Prospective Cohort Studies.

BACKGROUND: Prospective studies of red meat consumption and risk of stroke have provided inconsistent results. We aimed to assess this association by conducting a meta-analysis of prospective cohort studies. METHODS: Relevant studies were identified by searching PubMed and EMBASE through April 1, 2013. Summary relative risks (RR) and the corresponding 95% confidence intervals (CIs) were estimated by random-effect or fixed-effect models. RESULTS: Seven prospective cohort studies were included in the analyses, involving 2,079,236 subjects and 21,730 strokes cases. Total red meat consumption was associated with total stroke (RR = 1.14, 95% CI 1.05-1.24), cerebral infarction (RR = 1.13, 95% CI 1.0-1.28), and ischemic stroke (RR = 1.22, 95% CI 1.01-1.46). A significant association was found between consumption of processed red meat and total stroke (RR = 1.17, 95% CI 1.09-1.27). Consumption of fresh red meat was significantly associated with total stroke (RR = 1.13, 95% CI 1.04-1.22) and ischemic stroke (RR = 1.15, 95% CI 1.03-1.29). However, no evidence suggests that any type of meat was associated with hemorrhagic stroke. Also, no association was found between consumption of processed red meat and ischemic stroke (RR = 1.15, 95% CI .98-1.36) and between consumption of fresh red meat and cerebral infarction (RR = 1.06, 95% CI [.94, 1.20]). A significant risk for total stroke could be observed when the consumption of total red meat was above 50 g/day, processed red meat was just above 0 g/day, and fresh red meat was above 70 g/day. CONCLUSION: Our findings indicate that high consumption of red meat, especially processed red meat, will increase the risk of stroke.

C-reactive protein plays a marginal role in cognitive decline: a systematic review and meta-analysis.

OBJECTIVE: The objective of the study was to investigate the association between peripheral levels of C-reactive protein (CRP) and cognitive decline that is defined by 2-5 years of cognitive change in general cognitive function or specific cognitive domain. METHODS: We searched PubMed and Google for prospective/longitudinal studies that report the association between peripheral levels of CRP and risk of cognitive decline in the nondementia population. RESULTS: Out of 479 related articles from PubMed and Google, four studies with a total of 5255 non-demented subjects that report odds ratio (OR)/relative risk/hazard ratio of CRP levels and decline in general cognition met our criteria for meta-analysis. The association between higher levels of CRP and risk of global cognitive decline was weak but significant (OR, 1.27 [95% CI, 1.02 to 1.58]). However, the systematic review from six other articles that were not suitable for meta-analysis revealed a marginal association between CRP and cognitive decline in certain domains. CONCLUSION: Our analysis demonstrated a weak association between peripheral CRP level and global cognitive decline. Because of the small number of included studies and varied methodologies that they applied, caution should be taken when generalizing our finding to the full range of cognitive changes in different cognitive domains observed in non-demented people.

Association between myeloperoxidase G-463A polymorphism and lung cancer risk.

Many epidemiologic studies have investigated the association between myeloperoxidase (MPO) G-463A polymorphism and lung cancer risk, but the results were controversial. We performed a meta-analysis of 25 studies on MPO polymorphism and lung cancer risk published before July 2013. The allele of A was found to be associated with decreased risk of lung cancer compared with G allele (OR, 0.90; 95% CI, 0.82-0.98) in the general population. The significant association remained in the comparison between AA + AG and GG (OR, 0.92; 95% CI, 0.87-0.98). When it was stratified according to Asian population, the association between MPO polymorphism and lung cancer risk was further strengthened. However, no associations were found in the Caucasian population. This meta-analysis has demonstrated that MPO polymorphism might contribute to individual's susceptibility to lung cancer in Asian population. Caucasian authors could re-investigate the association between MPO polymorphism and lung cancer risk with more specific participants. Future studies focusing on interactions between combined genes and environmental risk factors are warranted.

Potent antitumor activity of HSP90 inhibitor AUY922 in adrenocortical carcinoma.

The objective of this study is to investigate the expression of HSP90 and the effect of HSP90 inhibitor AUY922 in ACC. The expression of HSP90 was measured in tissue samples from 36 human sporadic adrenocortical tumors by immunohistochemistry, Western blotting, and real-time PCR. The effect of AUY922 was tested on SW13 and H295R cells by evaluating cell viability and apoptosis in vitro. Transwell assay was performed to evaluate the migration of SW13 cells after different concentrations of AUY922. Western blot, real-time PCR, and immunohistochemistry revealed that both HSP90 mRNA and protein were obviously expressed in a higher degree in ACC tissues than ACA tissues and normal adrenal tissues (P < 0.01). Positive staining for HSP90 was found in 15 of 20 ACCs (75.00 %) and in 3 of 16 (18.75 %) ACAs. There existed the significant statistical difference (P < 0.001). AUY922 inhibited the proliferation of ACC cells in a time- and concentration-dependent manner, and increasing apoptosis was observed in tumor cells treated with the HSP90 inhibitor. Finally, migration of SW13 cells was distinctly suppressed after undergoing treatment with AUY922. Our data suggest that the specific HSP90 inhibitor AUY922 can play a therapeutic role in treatment of ACC and, thus, HSP90 could qualify as a promising new target in ACC.

Association between long-term exposure to fine particulate matter and its chemical constituents and premature death in individuals living with HIV/AIDS.

Long-term exposure to fine particulate matter (PM2.5) is associated with an increased total mortality. However, the association of PM2.5 with mortality in people living with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS, PLWHA) and the relationship between its constituents and adverse outcomes remain unknown. In this cohort study, 28,140 PLWHA were recruited from the HIV/AIDS Comprehensive Response Information Management System of the Hubei Provincial Centre for Disease Control and Prevention in China between 2001 and 2020. The annual PM2.5 chemical composition data, including sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), black carbon (BC), and organic matter (OM), was extracted from the Tracking Air Pollution (TAP) dataset in China. A Cox proportional hazard model with time-varying exposure and time-to-event quantile-based generalized (g) computation was used to assess the associations between PM2.5 chemical constituents, and mortality in PLWHA. A multivariate Cox proportional hazard model estimated an excess hazard ratio (eHR) of 0.32% [95% confidence interval (CI): (0.01%, 0.64%)] for AIDS-related death (ARD), associated with 1 µg/m3 rise in PM2.5 exposure. An increase of 1 µg/m3 in NH4+ was associated with 5.13% [95% CI: (2.89%, 7.43%)] and 2.97% [95% CI: (1.52%, 4.44%)] increase in the risk of ARD and all-cause deaths (ACD), respectively. When estimated using survival-based quantile g-computation, the eHR for ARD with a joint change in a decile increase in all five components was 6.10% [95% CI: 3.77%, 8.48%)]. Long-term exposure to PM2.5 chemical composition, particularly NH4+ increased the risk of death in PLWHA. This study provides epidemiological evidence that SO42- and NH4+ increased the risk of ARD and that NH4+ increased the risk of ACD in PLWHA. Multi-constituent analyses further suggested that NH4+ may be a key component in increasing the risk of premature death in patients with HIV/AIDS. Individuals aged ≥65 with HIV/AIDS are more vulnerable to SO42-, and consequent ACD.

The effects of fine particulate matter, solid fuel use and greenness on the risks of diabetes in middle-aged and older Chinese.

BACKGROUND: Previous studies provided clues that environmental factors were closely related to diabetes incidence. However, the evidence from high-quality and large cohort studies about the effects of PM2.5, solid fuel use and greenness on the development of diabetes among middle-aged and older adults in China was scarce. OBJECTIVE: To separately investigate the independent effects of PM2.5, solid fuel use and greenness on the development of diabetes among middle-aged and older adults. METHODS: A total of 9242 participants were involved in this study extracted from the China Health and Retirement Longitudinal Study. Time-varying Cox regression was applied to detect the association of diabetes with PM2.5, solid fuel use and greenness, separately. The potential interactive effect of air pollution and greenness were explored using the relative excess risk due to interaction (RERI). RESULTS: Per 10 µg/m3 increases in PM2.5 were associated with 6.0% (95% CI: 1.9, 10.2) increasing risks of diabetes incidence. Females seemed to be more susceptible to PM2.5. However, the effects of solid fuel use only existed in older and lower BMI populations, with hazard ratios (HRs) of 1.404 (1.116, 1.766) and 1.346 (1.057, 1.715), respectively. In addition, exposure to high-level greenness might reduce the risks of developing diabetes [HR = 0.801 (0.687, 0.934)]. Weak evidence of the interaction effect of PM2.5/solid fuel use and greenness on diabetes was found. SIGNIFICANCE: Both PM2.5 and solid fuel use were associated with the increasing incidence of diabetes. In addition, high-level greenness might be a beneficial environmental factor for reducing the risks of developing diabetes. All in all, our findings might provide valuable references for public health apartments to formulate very fruitful policies to reduce the burden of diabetes. IMPACT STATEMENT: Both PM2.5 and solid fuel use were associated with the increasing incidence of diabetes while high-level greenness was not, which might provide valuable references for public health apartments to make policies.

Global Burden of osteoarthritis associated with high body mass index in 204 countries and territories, 1990-2019: findings from the Global Burden of Disease Study 2019.

OBJECTIVE: To quantify the burden of osteoarthritis (OA) associated with high body mass index (BMI) across 204 countries and territories from 1990 to 2019. METHODS: This study extracted global, regional, and national data on years lived with disability (YLD) of OA associated with high BMI from GBD 2019. The YLD burden of OA associated with high BMI was systematically analyzed by age, SDI, sex, and EAPC. RESULTS: At the global level, ~2.67 million (95% UI: 1.04, 5.75) YLD were attributable to OA associated with high BMI, with an age-standardized rate of 31.9 (95% UI: 12.4, 68.75) YLD per 100,000 population in 2019. There was a 0.5 increase (95% UI: 0.35, 0.79) over the 30 years with an EAPC of 1.45. In 2019, Australasia {57.49 (95% UI: 23.62, 125.38)}, high-income North America {56.2 (95% UI: 23.32, 121.97)}, and Andean Latin America {49.77 (95% UI: 19.73, 111.73)} had the highest age-standardized YLD rates. The population aged at 60-74 group had a higher YLD rate for both males and females. Females tended to be more sensitive to the OA associated with high BMI than male in any region. CONCLUSIONS: In summary, the YLD rate of OA associated with high BMI presented a continuous upward trend in most countries. Women and older people are more sensitive to OA due to physiological and psychological factors. Controlling modifiable risk factors such as maintaining an appropriate BMI is needed for disease prevention.

Based on cuproptosis-related lncRNAs, a novel prognostic signature for colon adenocarcinoma prognosis, immunotherapy, and chemotherapy response.

Introduction: Colon adenocarcinoma (COAD) is a special pathological subtype of colorectal cancer (CRC) with highly heterogeneous solid tumors with poor prognosis, and novel biomarkers are urgently required to guide its prognosis. Material and methods: RNA-Seq data of COAD were downloaded through The Cancer Genome Atlas (TCGA) database to determine cuproptosis-related lncRNAs (CRLs) using weighted gene co-expression network analysis (WGCNA). The scores of the pathways were calculated by single-sample gene set enrichment analysis (ssGSEA). CRLs that affected prognoses were determined via the univariate COX regression analysis to develop a prognostic model using multivariate COX regression analysis and LASSO regression analysis. The model was assessed by applying Kaplan-Meier (K-M) survival analysis and receiver operating characteristic curves and validated in GSE39582 and GSE17538. The tumor microenvironment (TME), single nucleotide variants (SNV), and immunotherapy response/chemotherapy sensitivity were assessed in high- and low-score subgroups. Finally, the construction of a nomogram was adopted to predict survival rates of COAD patients during years 1, 3, and 5. Results: We found that a high cuproptosis score reduced the survival rates of COAD significantly. A total of five CRLs affecting prognosis were identified, containing AC008494.3, EIF3J-DT, AC016027.1, AL731533.2, and ZEB1-AS1. The ROC curve showed that RiskScore could perform well in predicting the prognosis of COAD. Meanwhile, we found that RiskScore showed good ability in assessing immunotherapy and chemotherapy sensitivity. Finally, the nomogram and decision curves showed that RiskScore would be a powerful predictor for COAD. Conclusion: A novel prognostic model was constructed using CRLs in COAD, and the CRLs in the model were probably a potential therapeutic target. Based on this study, RiskScore was an independent predictor factor, immunotherapy response, and chemotherapy sensitivity for COAD, providing a new scientific basis for COAD prognosis management.