Identification of novel biomarkers for lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is the second most common subtype of lung cancer, accounting for a majority of lung cancer-related deaths. Detection or diagnosis of cancer at an early stage is an unmet clinical need that is being actively explored. In this study, we aimed to identify potential biomarkers for LUSC, by screening expression status of all human genes against LUSC patient samples available with The Cancer Genome Atlas (TCGA). This led to the identification of several genes that are upregulated in LUSC. Further analysis revealed that many of these genes also show higher expression at the protein level not only in lung cancer but also in other cancers. Additionally, some of these genes show stage-dependent higher expression and are associated with statistically significant poor survival of LUSC patients. As per our results, more than 60 genes are overexpressed in LUSC at the level of mRNA and some at the protein level. Thus, we identified genes such as MCC1, MRPL47, CRYGS, HSP40, DNAJC19, GMPS and PARL as novel potential biomarkers for LUSC in this study. We believe that these genes hold great potential as LUSC biomarkers for early detection as the data are derived from patient samples. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03489-z.

Assessing the Vulnerability of Cancer Patients for COVID-19.

Severe acute respiratory syndrome involving corona virus-2 (SARS-CoV-2) has been implied to cause COVID-19 disease, leading to an unprecedented health emergency across the globe with a staggering figure of mortality rate. Measures to control the pandemic are pushing the economy into a tailspin, putting burden not only on the individuals but also on the nations. Despite the widespread infection rates, young people have shown better recovery rate while COVID-19 symptoms are more pronounced in elderly and people with comorbid conditions such as diabetes, cardiac and respiratory diseases. Cancer is a highly prevalent disease affecting millions of individuals. In this study, we analyzed the expression status of genes that are required for SARS-CoV-2 infectivity and its propagation to assess the susceptibility of certain cancer patients to infection and subsequent complications. Our data indicate that patients with colon, rectum, cholangiocarcinoma, lung adenoma, kidney renal papillary cell carcinoma and kidney renal clear cell carcinoma are more at risk for COVID-19. Genes that are responsible for severe COVID-19 are also highly expressed in many cancer types. We also carried out the association rule mining analysis which is helpful in predicting the expression of proviral genes in various cancers.

Identification of potential biomarkers for lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most predominant subtype of lung cancers and is one of the leading causes of cancer related mortality worldwide. Despite the advancements in the field of cancer diagnostics and therapeutics, detection at an early stage using reliable biomarkers is an unmet clinical need for a plethora of cancers, including LUAD, thus attributing to poor prognosis. In view of this, to identify potential biomarkers and therapeutic candidate genes, the expression of all known human genes was screened in the publicly available 'The Cancer Genome Atlas' (TCGA) samples of LUAD patients which resulted in the identification of overexpressed genes. Further analysis of these genes across various patient sample datasets revealed that ZNF687, ODR4, PBXIP1, PYGO2, METTL3, PIGM and RAD1 are consistently more highly expressed in LUAD. Higher expression of these genes either alone or in combination is correlated with poor survival of LUAD patients. Hence, in this study we propose that these identified genes could serve as potential candidates as gene signatures or biomarkers for LUAD that require further investigation in large cohorts of LUAD samples.

Most frequent South Asian haplotypes of ACE2 share identity by descent with East Eurasian populations.

It was shown that the human Angiotensin-converting enzyme 2 (ACE2) is the receptor of recent coronavirus SARS-CoV-2, and variation in this gene may affect the susceptibility of a population. Therefore, we have analysed the sequence data of ACE2 among 393 samples worldwide, focusing on South Asia. Genetically, South Asians are more related to West Eurasian populations rather than to East Eurasians. In the present analyses of ACE2, we observed that the majority of South Asian haplotypes are closer to East Eurasians rather than to West Eurasians. The phylogenetic analysis suggested that the South Asian haplotypes shared with East Eurasians involved two unique event polymorphisms (rs4646120 and rs2285666). In contrast with the European/American populations, both of the SNPs have largely similar frequencies for East Eurasians and South Asians, Therefore, it is likely that among the South Asians, host susceptibility to the novel coronavirus SARS-CoV-2 will be more similar to that of East Eurasians rather than to that of Europeans.

High frequencies of Non Allelic Homologous Recombination (NAHR) events at the AZF loci and male infertility risk in Indian men.

Deletions in the AZoospermia Factor (AZF) regions (spermatogenesis loci) on the human Y chromosome are reported as one of the most common causes of severe testiculopathy and spermatogenic defects leading to male infertility, yet not much data is available for Indian infertile men. Therefore, we screened for AZF region deletions in 973 infertile men consisting of 771 azoospermia, 105 oligozoospermia and 97 oligoteratozoospermia cases, along with 587 fertile normozoospermic men. The deletion screening was carried out using AZF-specific markers: STSs (Sequence Tagged Sites), SNVs (Single Nucleotide Variations), PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) analysis of STS amplicons, DNA sequencing and Southern hybridization techniques. Our study revealed deletion events in a total of 29.4% of infertile Indian men. Of these, non-allelic homologous recombination (NAHR) events accounted for 25.8%, which included 3.5% AZFb deletions, 2.3% AZFbc deletions, 6.9% complete AZFc deletions, and 13.1% partial AZFc deletions. We observed 3.2% AZFa deletions and a rare long AZFabc region deletion in 0.5% azoospermic men. This study illustrates how the ethnicity, endogamy and long-time geographical isolation of Indian populations might have played a major role in the high frequencies of deletion events.

A novel androgen receptor mutation resulting in complete androgen insensitivity syndrome and bilateral Leydig cell hyperplasia.

Androgens drive male secondary sexual differentiation and maturation. Mutations in the androgen receptor (AR) gene cause a broad spectrum of abnormal phenotypes in humans, ranging from mild through partial to complete androgen insensitivity. We have analyzed the AR gene by using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing and have studied gonads histologically in a familial case of complete androgen insensitivity syndrome. Sequence analysis of the AR gene showed a novel C2578T missense mutation, resulting in the replacement of a highly conserved leucine residue with phenylalanine (L859F) in ligand-binding domain of the receptor. The residue L859, located in helix 10 of the androgen receptor, plays a significant role in overall architecture of ligand-binding pocket. The mutation was absent from the father, normal brother of the patients, and 100 normal males recruited in this study as controls. The inheritance of the mutation in the family clearly shows that C2578T is the underlying mutation for the eventual phenotype in the patients. Histology of patient's gonads showed Leydig cell hyperplasia, with a few or no spermatogonium. It is thought that AR gene mutations result in hormonal imbalance, resulting in the high levels of luteinizing hormone (LH) and ultimately Leydig cell hyperplasia or tumor formation. In the present study, we have reported a rare familial case of Leydig cell hyperplasia despite consistently normal LH levels. The finding will help in giving counseling to this family and prevent the transmission of the mutated X chromosome to the coming generations.

Reconstructing the origin of Andaman Islanders.

The origin of the Andaman "Negrito" and Nicobar "Mongoloid" populations has been ambiguous. Our analyses of complete mitochondrial DNA sequences from Onges and Great Andaman populations revealed two deeply branching clades that share their most recent common ancestor in founder haplogroup M, with lineages spread among India, Africa, East Asia, New Guinea, and Australia. This distribution suggests that these two clades have likely survived in genetic isolation since the initial settlement of the islands during an out-of-Africa migration by anatomically modern humans. In contrast, Nicobarese sequences illustrate a close genetic relationship with populations from Southeast Asia.

Sperm mitochondrial mutations as a cause of low sperm motility.

We report the unique case of a 28-year-old man who, in spite of having a varicocele and a sperm concentration of 5 million/mL, of which 10% were motile and 20% had normal forms (oligoasthenoteratozoospermia [OAT]), was fertile. This was confirmed by paternity testing using 16 autosomal and 6 Y-chromosomal short tandem repeat (STR) loci. An analysis of mitochondrial genes that included cytochrome oxidase I (COI), cytochrome oxidase II (COII), adenosine triphosphate synthase6 (ATPase6), ATPase8, transfer ribonucleic acid (tRNA) serine I, tRNA lysine, and NADH dehydrogenase3 (ND3) revealed, for the first time, 9 missense and 27 silent mutations in the sperm's mitochondrial DNA (mtDNA) but not in the DNA from the blood cells. There was a 2-nucleotide deletion in the mitochondrial COII genes, introducing a stop codon, which might be responsible for low sperm motility.