CLPTM1L (CLPTM1 Like)

Finally, this study identified genetic susceptibility linked to 253 PC-related CpG sites. This study provides insights into the disease's origins and underscores potential targets for future research.

These findings suggest that lnc-MTPAP-1 may exert anti-apoptotic effects in lung cancer cells, and be involved in pollution-induced cancer progression. Further research should explore the therapeutic potential of targeting lnc-MTPAP-1, and better understand the molecular impact of PM exposure on lung cancer pathogenesis.

These results underscore the importance of modeling isoforms to maximize discovery of genetic risk mechanisms for cancers.

Importantly, SREBP1 overexpression markedly restored the inhibitory effects mediated by CLPTM1L and ERLIN2 knockdown, underscoring SREBP1 as a critical mediator in CLPTM1L's oncogenic role. These findings delineate a novel pathogenic mechanism in NPC, highlighting the KLF1/CLPTM1L/ERLIN2/SREBP1 regulatory cascade as a promising therapeutic target for NPC treatment.

We highlight several notable isoTWAS associations that demonstrate GWAS colocalization at the isoform level but not at the gene level, including, CLPTM1L (lung cancer), LAMC1 (colorectal), and BABAM1 (breast). These results underscore the critical importance of modeling isoform-level expression to maximize discovery of genetic risk mechanisms for cancers.

HPV infection was associated with increased CLPTM1L and TERT levels. Collectively, our results provide a link between cervical cancer risk variants, methylation, and gene expression and implicate both TERT and CLPTM1L as genes modulated by genomic background and HPV infection during cervical cancer development.

Smoking is an important risk factor for inducing the rs401681 and rs402710 variants and causes LC development in both populations. Other factors like non-smoking are mainly responsible for inducing the development of NSCLC in Asians, and is concentrated in LUAD among Asian non-smoking women.

CLPTM1L could impact cervical cancer cell proliferation and cisplatin-induced cell apoptosis, as well as cisplatin susceptibility in cervical cancer cells. This investigation has bestowed upon us novel insights into the pathogenesis of cervical cancer, underscoring the potential of CLPTM1L as a promising target for chemotherapeutic sensitization in the management of this malignancy.

The G allele variant of rs4975616 is negatively associated with the risk of LC and NSCLC (LUAD, LUSC). Compared with Asians, Caucasians are more likely to have a higher risk of LC and NSCLC (LUAD) due to the rs4975616 variant. In Caucasians, smoking and other factors like non-smoking contribute to rs4975616 variations leading to LC, and other factors like non-smoking also induce rs4975616 variations leading to NSCLC (LUAD). In Asians, smoking is the major risk factor for the induction of rs4975616 variations leading to LC and NSCLC(LUAD).

Furthermore, lung cancer risks were statistically significantly decreased for individuals possessing allele T through all genetic comparisons within Caucasians; whereas among Asians, significant reduction was observed solely in the TT vs. CC comparison. The present meta-analysis uncovers a significant association between the CLPTM1L rs401681 polymorphism and altered susceptibility to lung cancer.

These novel haplotype structures and miRNA:lncRNA interactions are important for understanding the common genetic link between cancers. These results can potentially be used in genetic panels.

Utilising multiple approaches for genetic correlation, locus and gene analysis, and causal assessment, we identify shared genetic susceptibilities and regulatory mechanisms. These findings reveal new leads and targets to further elucidate the genetic basis of lung and oesophageal carcinoma, aiding development of preventive and therapeutic strategies.